WorldWideScience

Sample records for 14c-labeled therapeutic dose

  1. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  2. Fate of 14C-labelled compounds in marine environment

    International Nuclear Information System (INIS)

    Model ecosystems have played an important role in predicting environmental behavior of agrochemicals. The microcosms used in these studies generally include soil units containing usual biotic components common for that ecosystem. In present studies, scope of two such ecosystems has been extended to study the fate of 14C-labelled pesticides in marine environment. 14C-labelled pesticides used in these studies were chlorpyrifos, DDT and HCH. Two systems were developed in laboratory simulating marine environment to study the fate of these pesticides. The first system was developed in an all glass aquarium tank with marine sediments, seawater, clams and algae and is referred to as marine ecosystem. The second system was developed to permit the total 14C-mass balance studies. It contained marine sediments under moist (60% water holding capacity) or flooded conditions and it is referred to as continuous flow system. Fate of 14C-DDT was studied in marine ecosystem while degradation of 14C-chlorpyrifos and 14C-HCH was studied in continuous flow system. 14C-DDT did not bioaccumulate in clams while at the end of 60 days 50% of the applied 14C-activity was present in sediment fraction of marine ecosystem. 14C-HCH degradation showed about 22-26% mineralization while 45-55% of the applied activity was recovered as organic volatiles. No significant bound residues were formed. 14C-chorpyrifos underwent considerable degradation in marine environment. TCP was the major degradation product. (author)

  3. Synthesis of two 14C-labeled catechol-o-methyltransferase inhibitors

    International Nuclear Information System (INIS)

    14C-labelled 3-(3,4-dihydroxy-5-nitrophenylmethylidene)-2,4-pentanedione and 14C-labelled E-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide have been synthesized from [carbonyl-14C]vanillin. (author)

  4. Systemic distribution of sup 14 C-labeled formaldehyde applied in the root canal following pulpectomy

    Energy Technology Data Exchange (ETDEWEB)

    Hata, G.I.; Nishikawa, I.; Kawazoe, S.; Toda, T.

    1989-11-01

    The systemic distribution of {sup 14}C-labeled formaldehyde which had been placed in the root canals of the canines of cats following pulpectomies was studied using liquid scintillation counting and whole-body autoradiographic technique. Radioactive {sup 14}C which had been placed in the canals was found in the plasma 30 min after the root canal procedure. The recovery of systemic {sup 14}C radioactivity increased with time. In addition, it seemed that approximately 3% of the dose placed in the teeth was excreted in the urine within 36 h. Whole-body autoradiograms indicated extensive concentration of {sup 14}C radioactivity in tissues other than those analyzed with the liquid scintillation technique.

  5. Excretion of 14C-labeled cyanide in rats exposed to chronic intake of potassium cyanide

    International Nuclear Information System (INIS)

    The excretion of an acute dose of 14C-labeled cyanide in urine, feces, and expired air was studied in rats exposed to daily intake of unlabeled KCN in the diet for 6 weeks. Urinary excretion was the main route of elimination of cyanide carbon in these rats, accounting for 83% of the total excreted radioactivity in 12 hr and 89% of the total excreted radioactivity in 24 hr. The major excretion metabolite of cyanide in urine was thiocyanate, and this metabolite accounted for 71 and 79% of the total urinary activity in 12 hr and 24 hr, respectively. The mean total activity excreted in expired air after 12 hr was only 4%, and this value did not change after 24 hr. Of the total activity in expired air in 24 hr, 90% was present as carbon dioxide and 9% as cyanide. When these results were compared with those observed for control rats, it was clear that the mode of elimination of cyanide carbon in both urine and breath was not altered by the chronic intake of cyanide

  6. Determination of 14C-labeled plasma L + α-alanine specific radioactivity

    International Nuclear Information System (INIS)

    A method is described, which enables the specific radioactivity of 14C-labeled L + α-alanine in plasma to be determined. Plasma alanine concentration is determined spectrophotometrically using alanine dehydrogenase. In a separate procedure, this enzyme is also used to convert 14C labeled alanine and added carrier alanine, to pyruvate. The phenylhydrazone derivative of the pyruvate is then prepared and assayed for radioactivity after crystallization to constant specific radioactivity. A maximum error of 1.5 percent for any one specific radioactivity determination was found. (U.S.)

  7. Facile and economical preparation of [14C]-labelled Shikimic acid

    International Nuclear Information System (INIS)

    A convenient and inexpensive method for the preparation of [14C]-labelled shikimic acid based on the photoassimilation of 14CO2 by henbane (Hyoscyamus niger L.) leaves in the presence of the herbicide glyphosate is described. Methanolic extracts were purified by successive anion exchange, paper and thin-layer chromatography to yield [14C]-labelled shikimic acid of 99.5% radiochemical purity, as shown by analytical HPLC. Under the conditions employed, the rate of incorporation of 14CO2 into shikimic acid (0.7-17.6%) showed a positive correlation with the size of the leaf used in the incubation (3.6-146 mg fresh weight), while the specific activity of the acid (6-12.7 GBq/mmol) was an inverse function of the leaf size. (author)

  8. 14C-labeled lignins as substrates for the study of lignin biodegradation and transformation

    International Nuclear Information System (INIS)

    Methods, both classical and isotopic, for quantifying lignin degradation are reviewed. Preparation and chemical characterization of 14C-labeled lignins (both synthetic and plant-synthesized) are reviewed, with emphasis on the utilization of these 14C-labeled substrates in biodegradation and biotransformation experiments. The scientific literature is reviewed concerning the use of 14C-lignins to examine the following: microbial groups that are able to degrade lignins; lignin degradation in natural environments; biochemistry and microbial physiology of lignin degradation; biodegradability of industrial lignins and their by-products; and screening for industrially valuable, lignin-modifying microorganisms. Recent results obtained in our laboratory concerning lignin degradation by eubacteria are presented. Future directions for 14C-methodology are examined

  9. Preparation of 14C-Labeled Multi-walled Carbon Nano-tubes for Biodistribution Investigations

    International Nuclear Information System (INIS)

    A new method allowing the 14C-labeling of carboxylic acid functions of carbon nano-tubes is described. The key step of the labeling process is a de-carbonylation reaction that has been developed and optimized with the help of a screening method. The optimized process has been successfully applied to multi-walled carbon nano-tubes (MWNTs), and the corresponding 14C-labeled nano-tubes were used to investigate their in vivo behavior. Preliminary results obtained after i.v. contamination of rats revealed liver as the main target organ. Radiolabeling of NTs with a long-life radioactive nucleus like 14C, coupled to a highly sensitive autoradiographic method, that provides a unique detection threshold, will make it possible to determine for a long time period whether or not NTs remain in any organs after animal exposure. (authors)

  10. Bacterial decomposition of synthetic 14C-labeled lignin and lignin monomer derivatives

    International Nuclear Information System (INIS)

    Nocardia sp. which was isolated from soil is capable of degrading synthetic lignin and utilizing its monomer derivatives. Decomposition was monitored by measuring the 14CO2 evolved and O2 consumed, when the bacterium was grown on a medium containing specifically 14C-labeled lignins or monomer phenolic compounds as major carbon source. The time course of the 14CO2 release and O2 uptake indicates a significant depolymerization and utilization of lignin by the Nocardia sp. (author)

  11. Stability of 125I and 14C labelled boom clay organic matter

    International Nuclear Information System (INIS)

    The candidate host formation for the disposal of radioactive waste in Belgium is boom clay which may contain up to 4% organic matter (OM). A limited fraction (less than 0.05%) of this OM is mobile. OM can complex radionuclides and so influence their migration. The migration behaviour of the OM itself has been extensively studied but to date such studies have used absorbancy measurements to quantify the OM. Unfortunately various problems accompany the use of absorbancy measurements. The particular problems may be overcome by using radiolabelled OM. Accordingly as a precursor to planned in situ migration experiments in boom clay (BC) using radiolabelled OM, stability studies on 125I and 14C labelled materials have been conducted. The 125I containing solutions were analysed using gel permeation chromatography (GPC) and the 14C solutions using high performance size exclusion chromatography (HPSEC). Dissappointingly at the relevant pH of 8.5, even in the absence of the clay, the 125I label was found to be unstable. However the 14C labelled OM (14C-BC-OM) was stable under the mild conditions employed in the test, so its stability was investigated in the presence of boom clay. The results were compared with that of 14C labelled humic acids (14C-HA), treated similarly. Unexpectedly the 14C labelled material was found to be partially unstable in the presence of boom clay. However the instability has not hampered the laboratory column experiments and should not hamper the proposed in situ experiments with this material. (orig.)

  12. Distribution of [14C]-labelled aflatoxin B1 in mice

    International Nuclear Information System (INIS)

    The distribution of [14C]-labelled aflatoxin B1 has been studied in mice with the aid of whole-body autoradiography. In addition to the localisation of labelled aflatoxin B1 and/or its metabolites in the liver, bile, kidney, lung and urine an uptake of 14C in the pigment of the Harderian gland and the eye was observed. Uptake of radioactivity was also found in the eyes of the foetuses although their livers did not accumulate radioactivity. (author)

  13. Fate of 14C-labeled microbial products derived from nitrifying bacteria in autotrophic nitrifying biofilms

    OpenAIRE

    Okabe, Satoshi; Kindaichi, Tomonori; Ito, Tsukasa

    2005-01-01

    The cross-feeding of microbial products derived from 14C-labeled nitrifying bacteria to heterotrophic bacteria coexisting in an autotrophic nitrifying biofilm was quantitatively analyzed by using microautoradiography combined with fluorescence in situ hybridization (MAR-FISH). After only nitrifying bacteria were labeled with [14C] bicarbonate, biofilm samples were incubated with and without NH4+ as a sole energy source for 10 days. The transfer of 14C originally incorporated into nitrifying b...

  14. Fate of 14C-Labeled Microbial Products Derived from Nitrifying Bacteria in Autotrophic Nitrifying Biofilms

    OpenAIRE

    Okabe, Satoshi; Kindaichi, Tomonori; Ito, Tsukasa

    2005-01-01

    The cross-feeding of microbial products derived from 14C-labeled nitrifying bacteria to heterotrophic bacteria coexisting in an autotrophic nitrifying biofilm was quantitatively analyzed by using microautoradiography combined with fluorescence in situ hybridization (MAR-FISH). After only nitrifying bacteria were labeled with [14C] bicarbonate, biofilm samples were incubated with and without NH4+ as a sole energy source for 10 days. The transfer of 14C originally incorporated into nitrifying b...

  15. Distribution of /sup 14/C-labelled ochratoxin A in pregnant mice

    Energy Technology Data Exchange (ETDEWEB)

    Appelgren, L.E.; Arora, R.G.

    1983-10-01

    Autoradiography was used to study the distribution of /sup 14/C-labelled ochratoxin A for up to 4 hr after its iv administration to mice at various stages of pregnancy. The highest /sup 14/C concentration was consistently found in the bile throughout the experimental period. The concentration of radioactivity in the tissues was found, in decreasing order, in the liver, kidney, blood, salivary glands, large vessels, brown fat, myocardium, uterus and lymphatic tissues. The toxin was shown to cross the placental barrier on day 9 of pregnancy, at which time it is most effective in producing fetal malformations.

  16. Modulation of (14) C-labeled glucose metabolism by zinc during aluminium induced neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2015-09-01

    Aluminium (Al) is one of the most prominent metals in the environment and is responsible for causing several neurological disorders, including Alzheimer's disease. On the other hand, zinc (Zn) is an essential micronutrient that is involved in regulating brain development and function. The present study investigates the protective potential of Zn in the uptake of (14) C-labeled amino acids and glucose and their turnover in rat brain slices during Al intoxication. Male Sprague Dawley rats (140-160 g) were divided into four different groups: normal control, Al treated (100 mg/kg body weight/day via oral gavage), Zn treated (227 mg/liter in drinking water), and Al + Zn treated. Radiorespirometric assay revealed an increase in glucose turnover after Al exposure that was attenuated after Zn treatment. Furthermore, the uptake of (14) C-labeled glucose was increased after Al treatment but was appreciably decreased upon Zn supplementation. In addition, the uptakes of (14) C-lysine, (14) C-leucine, and (14) C-aspartic acid were also found to be elevated following Al exposure but were decreased after Zn treatment. Al treatment also caused alterations in the neurohistoarchitecture of the brain, which were improved after Zn coadministration. Therefore, the present study suggests that Zn provides protection against Al-induced neurotoxicity by regulating glucose and amino acid uptake in rats, indicating that Zn could be a potential candidate for the treatment of various neurodegenerative disorders.

  17. Modulation of (14) C-labeled glucose metabolism by zinc during aluminium induced neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2015-09-01

    Aluminium (Al) is one of the most prominent metals in the environment and is responsible for causing several neurological disorders, including Alzheimer's disease. On the other hand, zinc (Zn) is an essential micronutrient that is involved in regulating brain development and function. The present study investigates the protective potential of Zn in the uptake of (14) C-labeled amino acids and glucose and their turnover in rat brain slices during Al intoxication. Male Sprague Dawley rats (140-160 g) were divided into four different groups: normal control, Al treated (100 mg/kg body weight/day via oral gavage), Zn treated (227 mg/liter in drinking water), and Al + Zn treated. Radiorespirometric assay revealed an increase in glucose turnover after Al exposure that was attenuated after Zn treatment. Furthermore, the uptake of (14) C-labeled glucose was increased after Al treatment but was appreciably decreased upon Zn supplementation. In addition, the uptakes of (14) C-lysine, (14) C-leucine, and (14) C-aspartic acid were also found to be elevated following Al exposure but were decreased after Zn treatment. Al treatment also caused alterations in the neurohistoarchitecture of the brain, which were improved after Zn coadministration. Therefore, the present study suggests that Zn provides protection against Al-induced neurotoxicity by regulating glucose and amino acid uptake in rats, indicating that Zn could be a potential candidate for the treatment of various neurodegenerative disorders. PMID:25908409

  18. Isolation of 14C labelled amino acids by biosynthesis in maize plants (Zea mais L.)

    International Nuclear Information System (INIS)

    A method of obtaining 14C labelled amino acids by biosynthesis in maize plants which had assimilated 14CO2, has been assayed. The plants were labelled for 60 minutes with 14CO2 produced from Ba 14CO3 (specific activity of 148 KBq/μmol). An extract of the soluble compounds was obtained with 80% ethanol and the amino acids were separated from the rest of the soluble compounds by ion exchange chromatography on column of Dowex 50-X8 resin. Finally, seventeen amino acids were isolated and identified from the purified extract. The acid amino acids were separated in anionic column (Dowex 1-X8) and the neutral and basic amino acids in cationic column (Dowex 50-X4). (Author) 56 refs

  19. Radioimmunoassay for anticollagen-antibodies using 14C-labelled collagen

    International Nuclear Information System (INIS)

    A sensitive radioimmunoassay for anticollagen antibodies is described. 14C-labelled human acid-soluble collagen of high specific activity (5 x 106 dpm/mg) is used as antigen either in native or denatured state. Experimentally induced anticollagen antibodies or RA synovial fluids containing antibodies to collagen are reacted with the labelled antigen. The immune complexes formed are precipitated with goat antiserum to rabbit globulins ('second antibody'). A systematic investigation of the labelled collagen in regard to cleavage by enzymes, fibril formation and specificity showed that no gross alteration had been caused by the labelling procedure. The assay furnishes information on the avidity, specificity and immunoglobulin class of experimental or pathological anticollagen antibodies. It can also be used as sensitive assay for collagen in biological fluids

  20. VI. A study of leaching of 14C-labelled coumaphos in soil columns

    International Nuclear Information System (INIS)

    Leaching of 14C-labelled coumaphos from aged dipping vat suspension was studied in 50 cm long x 20 cm diameter cores of undisturbed soil in mini-lysimeters. The vat suspension, previously aged for 6 months, was deposited to the top of the columns in lysimeters which were kept outdoors. The leachate was periodically collected over 6 months and analysed for radioactivity. At the end of this period soil columns were cut in 10 cm sections and the radioactivity present in each section was determined by combustion of homogenized soil samples. Radioactivity was also extracted from the soil samples with methanol by using Soxhlet apparatus and the extract analysed for total radioactivity. The extract was analysed by TLC for coumaphos and degradation products. No radioactivity was detected in the leachate. Most of the radioactivity (91-100%) was found in the top 10 cm section of the soil, indicating that coumaphos in the discarded waste does not leach below the top section of the soil and does not have high potential to contaminate ground water. Of the total radioactivity in the top section 62-75% was extractable and rest remained soil bound. The extractable radioactivity was coumaphos and no degradation products were detected. (author)

  1. Mineralization and Transfer Processes of 14C-labeled Pesticides in Outdoor Lysimeters

    International Nuclear Information System (INIS)

    A recently designed two-chamber-lysimeter-test-system allows the detailed investigation of degradation, transport and transfer processes of 14C-labeled substances in soil-plant-atmosphere-systems under outdoor conditions. With this test system it is feasible to distinguish between 14C-emissions from soil surfaces and 14C-emissions from plant surfaces in soil monoliths under real environmental conditions. Special soil humidity sensors allow the measurement of soil water content near to the soil surface, in 1 and 5 cm depth. The behavior of organic chemicals can be followed for a whole vegetation period and a mass balance for the applied chemical can be established. Some selected results of the herbicides isoproturon and glyphosate - using the two-chamber-lysimeter-test-system - are presented to demonstrate its applicability for the identification and quantification of the processes that govern pesticide behavior in soil-plant-systems. Mineralization of 14C-isoproturon was very different in four different soils; the mineralization capacity of the soils ranged from 2 to 60%. Leaching of isoproturon in general was very low, but depending on the soil type and environmental conditions isoproturon and its metabolites could be leached via preferential flow, especially shortly after application. For the herbicide 14C-glyphosate no accumulation of residues in the soil and no leaching of the residues to deeper soil layers could be observed after three applications. Glyphosate was rapidly degraded to AMPA in the soil. Glyphosate and AMPA were accumulated in soy bean nodules

  2. Enzymatic aryl-O-methyl-14C labeling of model lignin monomers

    International Nuclear Information System (INIS)

    Aryl-O-methyl ethers are abundant in aerobic and anaerobic environments. In particular, lignin is composed of units of this type. Lignin monomers specifically radiolabeled in methoxy, side chain, and ring carbons have been synthesized by chemical procedures and are important in studies of lignin synthesis and degradation, humus formation, and microbial O-demethylation. In this paper attention is drawn to an enzymatic procedure for preparing O-methyl-14C-labeled aromatic lignin monomers which has not previously been exploited in microbial ecology and physiology studies and which has several advantages compared with chemical synthesis procedures. O-[methyl-14C]vanillic and O-[methyl-14C]ferulic acids were prepared with S-[methyl-14C]adenosyl-L-methionine as the methyl donor, using commercially obtained porcine liver catechol-O-methyltransferase (EC 2.1.1.6). The specific activity of the methylated products was the same as that of the methyl donor, a maximum of about 58 μCi/μmol, and the yields were 42% (vanillate) and 35% (ferulate). Thus lignin monomers are readily prepared as O-methylated products of the catechol-O-methyltransferase reaction and, with this enzyme method of preparation, would be more widely available than labeled compounds which require chemical synthesis

  3. Modelling transport of 14C-labelled Natural Organic Matter (NOM) in Boom Clay

    International Nuclear Information System (INIS)

    In Belgium, the Boom Clay formation is considered to be the reference formation for HLW disposal R and D. Assessments to date have shown that the host clay layer is a very efficient barrier for the containment of the disposed radionuclides. Due to absence of significant water movement), diffusion - the dominant transport mechanism, combined with generally high retardation of radionuclides, leads to extremely slow radionuclide migration. However, trivalent lanthanides and actinides form easily complexes with the fulvic and humic acids which occur in Boom Clay and in its interstitial water. Colloidal transport may possibly result in enhanced radionuclide mobility, therefore the mechanisms of colloidal transport must be better understood. Numerical modeling of colloidal facilitated radionuclide transport is regarded an important means for evaluating its importance for long-term safety. The paper presents results from modeling experimental data obtained in the framework of the EC TRANCOM-II project, and addresses the migration behavior of relevant radionuclides in a reducing clay environment, with special emphasis on the role of the Natural Organic Matter (NOM)[1]. Percolation type experiments, using stable 14C-labelled NOM, have been interpreted by means of the numerical code HYDRUS-1D[2]. Tracer solution collected at regular intervals was used for inverse modeling with the HYDRUS-1D numerical code to identify the most likely migration processes and the associated parameters. Typical colloid transport submodels tested included kinetically controlled attachment/detachment and kinetically controlled straining and liberation. (authors)

  4. Decomposition of /sup 14/C-labelled lignin, holocellulose and lignocellulose by mycorrhizal fungi

    Energy Technology Data Exchange (ETDEWEB)

    Trojanowski, J.; Huettermann, A.; Haider, K.

    1984-01-01

    Five different species of known ecto-mycorrhizal fungi: Cenococcum geophilum, Amanita muscaria, Tricholoma aurantium, Rhizopogon luteolus and Rhizopogon roseolus were studied for their ability to metabolize the major components of plant cell walls. All strains were able to decompose /sup 14/C-labelled plant lignin, /sup 14/C-lignocellulose and /sup 14/C-DHP-lignin at a rate which was lower than the one observed for the known white rot fungi Heterobasidion annosum and Sporotrichum pulverulentum. Also /sup 14/C-(U)-holocellulose was relatively less degradable for the mycorrhizal fungi than for the white rotters. On the other hand, aromatic monomers like /sup 14/C-vanillic acid were decomposed to a much higher extent by two species of mycorrhizal fungi compared to the activity observed for Heterobasidion annosum. The results of the experiments reveal that these stains of mycorrhizal fungi are well able to utilize the major components of plant material and thus can contribute to litter decomposition in the forest floor.

  5. Synthesis of 14C-labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)

    International Nuclear Information System (INIS)

    14C-labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (2, RDX) was prepared by nitrolysis of hexahydro-1,3,5-tripropionyl-1,3,5-triazine (1) for bioenvironmental studies. 1 was synthesized from paraformaldehyde and propionitrile by a modified method reported earlier. (Author)

  6. Biokinetics and radiation dosimetry of 14C-labelled triolein, urea, glycocholic acid and xylose in man. Studies related to nuclear medicine 'breath tests' using accelerator mass spectrometry

    International Nuclear Information System (INIS)

    14C-labelled substances have been used in biomedical research and clinical medicine for over 50 years. Physicians and scientists however, often hesitate to use these substances in patients and volunteers because the radiation dosimetry is unclear. In this work detailed long-term biokinetic and dosimetric estimation have been carried out for four clinically used 14C-breath tests: 14C-triolein (examination of fat malabsorption), urea (detection of Helicobacter pylori infection in the stomach), glycocholic acid and xylose (examination of bacterial overgrowth in the small intestine) by using the highly sensitive accelerator mass-spectrometry (AMS) technique. The AMS technique has been used to measure low 14C concentrations in small samples of exhaled air, urine, faeces and tissue samples and has improved the base for the estimation of the absorbed dose to various organs and tissues and the effective dose to man. The high sensitivity of the AMS system has also made it possible to perform 14C breath tests on patient groups which were earlier subject for restriction (e.g. small children). In summary, our results show that for adult patients - and in the case of 14C-urea breath test also for children down to 3 years of age - the dose contributions are comparatively low, both described as organ doses and as effective doses. For adults, the latter is: 14C-glycocholic acid - 0.4 mSv/MBq, 14C-triolein - 0.3 mSv/MBq, 14C-xylose - 0.1 mSv/MBq and 14C-urea - 0.04 mSv/MBq. Thus, from a radiation protection point of view there is no reason for restrictions in using any of the 14C-labelled radiopharmaceutical included in this work in the activities normally used (0.07-0.2 MBq for a 70 kg patient)

  7. Dynamics of {sup 14}C-labeled glucose and ammonium in saline arable soils

    Energy Technology Data Exchange (ETDEWEB)

    Vuelvas-Solorzano, Alma; Hernandez-Matehuala, Rosalina [Instituto Tecnologico de Celaya, Celaya Gto. (Mexico). Dept. de Ing. Bioquimica. Lab. de Bioingenieria; Conde-Barajas, Eloy; Cardenas-Manriquez, Marcela [Instituto Tecnologico de Celaya, Celaya Gto. (Mexico). Dept. de Ing. Ambiental. Lab. de Bioingenieria], e-mail: marcela@itc.mx; Luna-Guido, Marco L.; Dendooven, Luc [Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (Cinvestav), D.F. (Mexico). Dept. de Biotecnologia y Bioingenieria. Lab. de Ecologia de Suelos], e-mail: dendoove@cinvestav.mx

    2009-07-15

    Organic matter dynamics and nutrient availability in saline agricultural soils of the State of Guanajuato might provide information for remediation strategies. {sup 14}C labeled glucose with or without 200 mg kg{sup -}1 of NH{sub 4} {sup +}-N soil was added to two clayey agricultural soils with different electrolytic conductivity (EC), i.e. 0.94 dS m{sup -}1 (low EC; LEC) and 6.72 dS m{sup -}1 (high EC; HEC), to investigate the effect of N availability and salt content on organic material decomposition. Inorganic N dynamics and production of CO{sub 2} and {sup 14}CO{sub 2} were monitored. Approximately 60 % of the glucose-{sup 14}C added to LEC soil evolved as {sup 14}CO{sub 2}, but only 20 % in HEC soil after the incubation period of 21 days. After one day, < 200 mg {sup 14}C was extractable from LEC soil, but > 500 mg {sup 14}C from HEC soil. No N mineralization occurred in the LEC and HEC soils and glucose addition reduced the concentrations of inorganic N in unamended soil and soil amended with NH{sub 4}{sup +}-N. The NO{sub 2}{sup -} and NO{sub 3}{sup -} concentrations were on average higher in LEC than in HEC soil, with exception of NO{sub 2}{sup -} in HEC amended with NH{sub 4}{sup +}-N. It was concluded that increases in soil EC reduced mineralization of the easily decomposable C substrate and resulted in N-depleted soil. (author)

  8. Mineralization and Transfer Processes of {sup 14}C-labeled Pesticides in Outdoor Lysimeters

    Energy Technology Data Exchange (ETDEWEB)

    Grundmann, Sabine; Doerfler, Ulrike, E-mail: doerfler@gsf.de; Ruth, Bernhard; Loos, Christine [GSF - National Research Center for Environment and Health, Institute of Soil Ecology (Germany); Wagner, Tobias [GSF - National Research Center for Environment and Health, Institute of Biochemical Plant Pathology (Germany); Karl, Heidrun; Munch, Jean Charles; Schroll, Reiner [GSF - National Research Center for Environment and Health, Institute of Soil Ecology (Germany)

    2008-04-15

    A recently designed two-chamber-lysimeter-test-system allows the detailed investigation of degradation, transport and transfer processes of {sup 14}C-labeled substances in soil-plant-atmosphere-systems under outdoor conditions. With this test system it is feasible to distinguish between {sup 14}C-emissions from soil surfaces and {sup 14}C-emissions from plant surfaces in soil monoliths under real environmental conditions. Special soil humidity sensors allow the measurement of soil water content near to the soil surface, in 1 and 5 cm depth. The behavior of organic chemicals can be followed for a whole vegetation period and a mass balance for the applied chemical can be established. Some selected results of the herbicides isoproturon and glyphosate - using the two-chamber-lysimeter-test-system - are presented to demonstrate its applicability for the identification and quantification of the processes that govern pesticide behavior in soil-plant-systems. Mineralization of {sup 14}C-isoproturon was very different in four different soils; the mineralization capacity of the soils ranged from 2 to 60%. Leaching of isoproturon in general was very low, but depending on the soil type and environmental conditions isoproturon and its metabolites could be leached via preferential flow, especially shortly after application. For the herbicide {sup 14}C-glyphosate no accumulation of residues in the soil and no leaching of the residues to deeper soil layers could be observed after three applications. Glyphosate was rapidly degraded to AMPA in the soil. Glyphosate and AMPA were accumulated in soy bean nodules.

  9. Bioavailability of bound residue derived from 14 C-labeled chlorsulfuron in soil and its mechanism of phytotoxicity

    Institute of Scientific and Technical Information of China (English)

    YE Qing-fu; WU Jian-min; SUN Jin-he

    2004-01-01

    The bioavailability of bound residue(BR) derived from 14 C-labeled chlorsulfuron in soil and effect of themain components of the BR on growth of rape( brassica napus) and rice( Oryza sativa L. ) were investigated. Theresults showed that the BR with the concentration of 0.28 and 0.56 nmol/g air-dried soil, which was calculated byspecial radioactivity of 14C-labeled chlorsulfuron parent compound, resulted in significant depression effect on growthof rape seedling. It was assured that the main components(2-amino-4-methoxyl-6-methyl-1,3,5-triazine, 2-amino-4-hydroxyl-6-methyl-1,3,5-triazine, and 2-chloro-benzenesul-fonamide) of the BR did not inhibit the growth of rape andrice. LC-MS analysis demonstrated that the parent compound previously bound to the soil matrix could be againreleased and transformed into methanol-extractable residue during the course of rape growth. It was concluded thatthe molecular leading to the phytotoxicity to rape and rice in the BR is still the parent compound.

  10. Fate of {sup 14}C-labeled dissolved organic matter in paddy and upland soils in responding to moisture

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiangbi [Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125 (China); Huanjiang Observation and Research Station for Karst Ecosystems, Huanjiang 547100 (China); Wang, Aihua [Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125 (China); Li, Yang; Hu, Lening; Zheng, Hua; He, Xunyang [Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125 (China); Huanjiang Observation and Research Station for Karst Ecosystems, Huanjiang 547100 (China); Ge, Tida; Wu, Jinshui [Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125 (China); Kuzyakov, Yakov [Department of Soil Science of Temperate Ecosystems, Department of Agricultural Soil Science, University of Göttingen, 37077 Göttingen (Germany); Su, Yirong, E-mail: yrsu@isa.ac.cn [Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125 (China); Huanjiang Observation and Research Station for Karst Ecosystems, Huanjiang 547100 (China)

    2014-08-01

    Soil organic matter (SOM) content in paddy soils is higher than that in upland soils in tropical and subtropical China. The dissolved organic matter (DOM) concentration, however, is lower in paddy soils. We hypothesize that soil moisture strongly controls the fate of DOM, and thereby leads to differences between the two agricultural soils under contrasting management regimens. A 100-day incubation experiment was conducted to trace the fate and biodegradability of DOM in paddy and upland soils under three moisture levels: 45%, 75%, and 105% of the water holding capacity (WHC). {sup 14}C labeled DOM, extracted from the {sup 14}C labeled rice plant material, was incubated in paddy and upland soils, and the mineralization to {sup 14}CO{sub 2} and incorporation into microbial biomass were analyzed. Labile and refractory components of the initial {sup 14}C labeled DOM and their respective half-lives were calculated by a double exponential model. During incubation, the mineralization of the initial {sup 14}C labeled DOM in the paddy soils was more affected by moisture than in the upland soils. The amount of {sup 14}C incorporated into the microbial biomass (2.4–11.0% of the initial DOM-{sup 14}C activity) was less affected by moisture in the paddy soils than in the upland soils. At any of the moisture levels, 1) the mineralization of DOM to {sup 14}CO{sub 2} within 100 days was 1.2–2.1-fold higher in the paddy soils (41.9–60.0% of the initial DOM-{sup 14}C activity) than in the upland soils (28.7–35.7%), 2) {sup 14}C activity remaining in solution was significantly lower in the paddy soils than in the upland soils, and 3) {sup 14}C activity remaining in the same agricultural soil solution was not significantly different among the three moisture levels after 20 days. Therefore, moisture strongly controls DOM fate, but moisture was not the key factor in determining the lower DOM in the paddy soils than in the upland soils. The UV absorbance of DOM at 280 nm

  11. Techniques Used in the Application of a 14C-Labelled Herbicide

    International Nuclear Information System (INIS)

    The butylic ester of 2.4-D-214C was used to apply the herbicide in the chemical form adopted for field spraying. Esterification of the acid was carried out in the Labelled Molecules Division of the National Atomic Energy Commission's Department of Scientific Research. For purposes of the experiment the ester was prepared in the form of two emulsions of different concentrations ('concentrated' and 'dilute'), the first being based on the average amount used in field application in Argentina. The remaining components of the emulsions, i.e. the emulsifier and the solvent, were these normally used in Argentina, since in this country the import of herbicides based on 2,4-D is not permitted. The tests were carried out on specimens of quinoa (Chenopodium spp.), Datura ferox and Cyperus (Cyperus rotundus), kept in greenhouses. The duration of the treatment was three days in all cases except in that of Cyperus, where it was twelve days. The distribution of the radioisotope in the plants following application of the labelled substance was always limited, as was shown by the autoradiographs. All the doses used proved to be suitable for obtaining autoradiographs, including the lowest dose, containing 0.118 μCi of activity in the least of the volumes used (10 A). Quantitative determination of the percentage of the dose (amount of radioactivity) localized in a quinoa plant gave a figure of 16.3%. (author)

  12. The transformation and translocation of 14C-labelled glucose in the course of granulation development of Batangas mandarin fruits

    International Nuclear Information System (INIS)

    In the middle of storage period for Batangas mandarin fruits, the fruits segment was injected with 14C-labelled glucose. Radioisotope was found in the rind and non-injected segments of the granulated fruits or normal fruits. The results showed that the radioactivity in the rind of slight-granulated fruits was significantly lower than that in normal fruits. The diffusion of 14C-labelled glucose to the rind or to the segments of slightly granulated fruits was significantly higher than that of normals. These results indicated that granulation was not caused by the shift of nutritive matter from the juice sac to the rind but likely by its senescence. In the course of granulation development, the radioactivity of insoluble carbohydrate of the juice sac in severely granulated fruits was 24.65% of the total sac radioactivity. However, it was only 6.41% in normal fruits. Although the radioactivity in the rind of granulated fruits was lower than that in normal fruits, it increased faster. The respiratory rate of medium granulated fruit was 17.18 CO2 ml/kg·h and that of severely granulated fruit was 23.64 CO2 mol/kg·h. Both were significantly higher than that of normal fruits (11.03 CO2 ml/kg·h). It was suggested that the sharp loss of soluble nutritive matter in the juice sac of granulated fruits might result from their transformation into insoluble matter, translocation to the rind and respiration consumption

  13. The cerebral metabolism of amino acids and related metabolites as studied by 13C and 14C labelling

    International Nuclear Information System (INIS)

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by 13C-and 14C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [13C[acetate, it was shown that glial cells export ∼60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [13C[glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of 13CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs

  14. A microcosm system to evaluate the fate of 14C labelled pesticides in soils from different climate zones

    International Nuclear Information System (INIS)

    A method for quantifying and comparing the processes relevant to the fate of pesticides in soils from various climate zones - volatilization, mineralization, transport and leaching - was developed. A microcosm, consisting of an undisturbed soil column in a round metal cylinder (height 30 cm, 15 cm inner diameter), is fitted with devices to collect and analyze the leachate and to investigate the gas phase above the soil surface. To include all the conversion products in the investigations, 14C labelled pesticides are used. Thus, determination of the complete 14C mass balance is possible. As the first model herbicide, 14C-terbuthylazine was used. Ventilation was based on a wind speed of 1 m/s; irrigation, based on an average rainfall of 600 mm/a, was applied discontinuously, interrupted by dry periods. Soils from Brazil, China and Germany were investigated in four replicates each. Soil from Brazil, with the highest organic matter and clay contents, exhibited the lowest volatilization of 14C-terbuthylazine, the highest mineralization to 14CO2, the lowest vertical transport and the lowest leaching of 14C into the percolate water, followed by the soils from China and Germany. Soil from Germany showed the highest volatilization, the highest vertical transport and the highest leaching rates. These findings demonstrate that the properties of soils, as formed under different climatic conditions, influence the fate and persistence of a pesticide in the soil environment. (author). 5 refs, 1 fig., 3 tabs

  15. The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling

    Energy Technology Data Exchange (ETDEWEB)

    Hassel, B.

    1995-11-01

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by {sup 13}C-and {sup 14}C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [{sup 13}C]acetate, it was shown that glial cells export {approx}60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [{sup 13}C]glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of {sup 13}CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs.

  16. Study of whey fermentation by kefir immobilized on low cost supports using 14C-labelled lactose.

    Science.gov (United States)

    Soupioni, Magdalini; Golfinopoulos, Aristidis; Kanellaki, Maria; Koutinas, Athanasios A

    2013-10-01

    Brewer's Spent Grains (BSG) and Malt Spent Rootlets (MSR) were used as supports for kefir cells immobilization and the role of lactose uptake rate by kefir in the positive activity of produced biocatalysts during whey fermentation was investigated. Lactose uptake rate by the immobilized cells was recorded using (14)C-labelled lactose and the effect of various conditions (pH, temperature and kind of support) on it and consequently on fermentation time and ethanol production was examined. The results showed that lactose uptake rate was correlated to fermentation rate and increased as temperature was increased up to 30°C at pH 5.5. The same results have been recently noticed by using biocatalysts with Delignified Cellulosic Materials (DCM) and Gluten Pellets (GP), but fermentation time of about 7h by kefir immobilized on DCM and BSG resulted to two fold lower than that on GP and MSR. The highest alcohol concentration was observed by MSR. PMID:23385156

  17. Biokinetics and radiation dosimetry of {sup 14}C-labelled triolein, urea, glycocholic acid and xylose in man. Studies related to nuclear medicine 'breath tests' using accelerator mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Gunnarsson, Mikael

    2002-08-01

    {sup 14}C-labelled substances have been used in biomedical research and clinical medicine for over 50 years. Physicians and scientists however, often hesitate to use these substances in patients and volunteers because the radiation dosimetry is unclear. In this work detailed long-term biokinetic and dosimetric estimation have been carried out for four clinically used {sup 14}C-breath tests: {sup 14}C-triolein (examination of fat malabsorption), urea (detection of Helicobacter pylori infection in the stomach), glycocholic acid and xylose (examination of bacterial overgrowth in the small intestine) by using the highly sensitive accelerator mass-spectrometry (AMS) technique. The AMS technique has been used to measure low {sup 14}C concentrations in small samples of exhaled air, urine, faeces and tissue samples and has improved the base for the estimation of the absorbed dose to various organs and tissues and the effective dose to man. The high sensitivity of the AMS system has also made it possible to perform {sup 14}C breath tests on patient groups which were earlier subject for restriction (e.g. small children). In summary, our results show that for adult patients - and in the case of {sup 14}C-urea breath test also for children down to 3 years of age - the dose contributions are comparatively low, both described as organ doses and as effective doses. For adults, the latter is: {sup 14}C-glycocholic acid - 0.4 mSv/MBq, {sup 14}C-triolein - 0.3 mSv/MBq, {sup 14}C-xylose - 0.1 mSv/MBq and {sup 14}C-urea - 0.04 mSv/MBq. Thus, from a radiation protection point of view there is no reason for restrictions in using any of the {sup 14}C-labelled radiopharmaceutical included in this work in the activities normally used (0.07-0.2 MBq for a 70 kg patient)

  18. Comparison of the degradation of 14C-labeled DHP and corn stalk lignins by micro- and macrofungi and bacteria

    International Nuclear Information System (INIS)

    To what extent and by which mode microfungi and bacteria from soil are able to degrade lignin have been investigated and their activity compared with those of white and brown rot Basidiomycetes. The experiments were made by means of specifically 14C-labeled DHPs prepared by polymerization of correspondingly labeled coniferyl alcohol. Also, a corn stalk material was used which was specifically labeled in the lignin part. This material was prepared by infusion of specifically labeled cinnamic acid compounds into growing maize plants. The potential of the organisms to degrade several specifically labeled phenols was determined and compared. White and brown rot fungi, as well as several microscopic fungi, were able to degrade phenolcarboxylic and cinnamic acids and even some phenolic compounds with completely alkylated phenolic hydroxl groups. They could also introduce hydroxl groups into benzoic and pi-hydroxybenzoic acids before ring cleavage. As compared to brown rot, the white rot fungi released higher amounts of CO2 from the aromatic and side chain carbons of DHP and plant lignins. Some brown rot fungi, however, had similar capacities in degrading DHP lignin as white rot fungi. They especially released more CO2 from methoxyl groups. This release was dependent upon the added carbohydrate source and could be either repressed or enhanced. Several bacteria, especially Nocardia spp. and Pseudomonas spp., were tested for their potential to degrade the labeled lignins or phenols. Most of these bacteria did not appreciably degrade lignins, although they were highly active in the metabolization of phenols. Some Nocardia spp., however, were found to have a noteworthy capacity in the degradation of lignins and phenols. Preliminary studies of the potentials of the organisms to attack labeled lignin sulfonates either in liquid or soil cultures are presented. (Refs. 100)

  19. Production of the {sup 14}C-labeled insecticidal protein Cry1Ab for soil metabolic studies using a recombinant Escherichia coli in small-scale batch fermentations

    Energy Technology Data Exchange (ETDEWEB)

    Valldor, Petra; Miethling-Graff, Rona; Dockhorn, Susanne; Martens, Rainer; Tebbe, Christoph C. [Federal Research Institute for Rural Areas, Forestry and Fisheries, Braunschweig (Germany). Thuenen Institute (vTI) for Biodiversity

    2012-10-15

    Insecticidal Cry proteins naturally produced by Bacillus thuringiensis are a major recombinant trait expressed by genetically modified crops. They are released into the soil during and after cropping. The objective of this study was to produce {sup 14}C-labeled Cry1Ab proteins for soil metabolic studies in scope of their environmental risk assessment. Cry1Ab was synthesized as a protoxin by Escherichia coli HB101 pMP in 200-mL liquid batch culture fermentations and purified from inclusion bodies after trypsin digestion. For cultivation, U-{sup 14}C-glycerol was the main carbon source. Inclusion bodies were smaller and Cry1Ab yield was lower when the initial amount of total organic carbon in the cultivation broth was below 6.4 mg C L{sup -1}. Concentrations of 12.6 g {sup 14}C-labeled glycerol L{sup -1} (1 % v/v) resulted in the production of 17.1 mg {sup 14}C-Cry1Ab L{sup -1} cultivation medium. {sup 14}C mass balances showed that approx. 50 % of the label was lost by respiration and 20 % remained in the growth media, while the residual activity was associated with biomass. Depending on the production batch, 0.01 to 0.05 % of the total {sup 14}C originated from Cry1Ab. In the presence of 2.04 MBq {sup 14}C-labeled carbon sources, a specific activity of up to 268 Bq mg{sup -1} {sup 14}C-Cry1Ab was obtained. A more than threefold higher specific activity was achieved with 4.63 MBq and an extended cultivation period of 144 h. This study demonstrates that {sup 14}C-labeled Cry1Ab can be obtained from batch fermentations with E. coli in the presence of a simple {sup 14}C-labeled carbon source. It also provides a general strategy to produce {sup 14}C-labeled proteins useful for soil metabolic studies. (orig.)

  20. 14C-labeled propionate metabolism in vivo and estimates of hepatic gluconeogenesis relative to Krebs cycle flux.

    Science.gov (United States)

    Landau, B R; Schumann, W C; Chandramouli, V; Magnusson, I; Kumaran, K; Wahren, J

    1993-10-01

    Purposes of this study were 1) to estimate in humans, using 14C-labeled propionate, the rate of hepatic gluconeogenesis relative to the rate of Krebs cycle flux; 2) to compare those rates with estimates previously made using [3-14C]lactate and [2-14C]acetate; 3) to determine if the amount of ATP required for that rate of gluconeogenesis could be generated in liver, calculated from that rate of Krebs cycle flux and splanchnic balance measurements, previously made, and 4) to test whether hepatic succinyl-CoA is channeled during its metabolism through the Krebs cycle. [2-14C]propionate, [3-14C]-propionate, and [2,3-14C]succinate were given along with phenyl acetate to normal subjects, fasted 60 h. Distributions of 14C were determined in the carbons of blood glucose and of glutamate from excreted phenylacetylglutamine. Corrections to the distributions for 14CO2 fixation were made from the specific activities of urinary urea and the specific activities in glucose, glutamate, and urea previously found on administering [14C]-bicarbonate. Uncertainties in the corrections and in the contributions of pyruvate and Cori cyclings limit the quantitations. The rate of gluconeogenesis appears to be two or more times the rate of Krebs cycle flux and pyruvate's decarboxylation to acetyl-CoA, metabolized in the cycle, less than one-twenty-fifth the rate of its decarboxylation. Such estimates were previously made using [3-14C]lactate. The findings support the use of phenyl acetate to sample hepatic alpha-ketoglutarate. Ratios of specific activities of glucose to glutamate and glucose to urinary urea and expired CO2 indicate succinate's extensive metabolism when presented in trace amounts to liver. Utilizations of the labeled compounds by liver relative to other tissues were in the order succinate = lactate > propionate > acetate. ATP required for gluconeogenesis and urea formation was approximately 40% of the amount of ATP generated in liver. There was no channeling of succinyl-CoA in

  1. Fate of pyribambenz propyl (ZJ0273) in anaerobic soils revealed by position-specific {sup 14}C labeling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei [Institute of Nuclear Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Department of Environmental Sciences, University of California, Riverside, CA 92521 (United States); Yue, Long; Zhang, Sufen [Institute of Nuclear Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Ye, Qingfu, E-mail: qfye@zju.edu.cn [Institute of Nuclear Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Qi, Wenyuan, E-mail: sunny0123@vip.163.com [Shanghai Academy of Agriculture Science, Shanghai 201106 (China); Wang, Haiyan; Chen, Ziyuan [Institute of Nuclear Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China)

    2013-08-15

    Highlights: • The time-dependent transformation of ZJ0273 in flooding soils was explained. • ZJ0273 showed long persistence, low mineralization and weak transport potential. • Phase distribution of {sup 14}C residue depended both on soil type and labeling position. • ZJ0273 tend to form bound residues in submerged soils. •Specific {sup 14}C labeling is an improved tracing technique for fate characterization. -- Abstract: Pyribambenz propyl, or ZJ0273, is a new and widely used pyrimidynyloxybenzoic herbicide; however, its behavior and safety in anaerobic soils remain poorly understood. In this study, ZJ0273 was labeled with {sup 14}C on its benzoate-, pyrimidyl- and benzyl- rings respectively, and applied to anoxic flooding soils to characterize its anaerobic fates. Over the 100 d incubation, the amended {sup 14}C-ZJ0273 was slightly mineralized to {sup 14}CO{sub 2} (<4%) or redistributed into the overlaying water (<10%), with the majority of the {sup 14}C (82–98%) remaining in the soil. The residues in soil underwent a gradual transformation from extractable residues (ER) to bound residues (BR), with the percentage of {sup 14}C-BR increasing from 1.1 to 2.5% at day 5 to 23.2–47.2% at day 100. The proportion of {sup 14}C-ER, {sup 14}C-BR and {sup 14}CO{sub 2} depended both on the soil property and the labeling position. Generally, ZJ0273 has the highest tendency to form BR in fluvio-marine yellow loamy soil, and the mineralization on both the benzoate and benzyl rings tends to be more extensive in red-clayed soil than the other soils. The ring-specific labeling {sup 14}C on three aromatic rings respectively provides full molecular information and yield information on sub-molecular level, i.e., the benzoate ring was generally more susceptible to cleavage than the pyrimidyl or benzyl rings (P < 0.01)

  2. A Radiochemical Biotechnological Approach: Preliminary Study of Lactose Uptake Rate by Kefir Cells, Using 14C-labeled Lactose, in Anaerobic Fermentation

    Science.gov (United States)

    Golfinopoulos, A.; Soupioni, M.; Kanellaki, M.; Koutinas, A. A.

    2008-08-01

    The effect of initial lactose concentration on lactose uptake rate by kefir free cells, during the lactose fermentation, was studied in this work. For the investigation 14C-labelled lactose was used due to the fact that labeled and unlabeled molecules are fermented in the same way. The results illustrated lactose uptake rates are about up to two fold higher at lower initial ∘Bé densities as compared with higher initial ∘Bé densities.

  3. Therapeutic effects of low radiation doses

    International Nuclear Information System (INIS)

    This editorial explores the scientific basis of radiotherapy with doses of < 1 Gy for various non-malignant conditions, in particular dose-effect relationships, risk-benefit considerations and biological mechanisms. A review of the literature, particularly clinical and experimental reports published more than 50 years ago was conducted to clarify the following problems. 1. The dose-response relationships for the therapeutic effects on three groups of conditions: non-malignant skin disease, arthrosis and other painful degenerative joint disorders and anti-inflammatory radiotherapy; 2. risks after radiotherapy and after the best alternative treatments; 3. the biological mechanisms of the different therapeutic effects. Radiotherapy is very effective in all three groups of disease. Few dose-finding studies have been performed, all demonstrating that the optimal doses are considerable lower than the generally recommended doses, yet few of these studies meet the required standard. In different conditions, risk-benefit analysis of radiotherapy versus the best alternative treatment yields very different results: whereas radiotherapy for acute postpartum mastitis may not be justified any more, the risk-benefit ratio of radiotherapy of other conditions and particularly so in dermatology and some anti-inflammatory radiotherapy appears to be more favourable than the risk-benefit ratio of the best alternative treatments. Radiotherapy can be very effective treatment for various non-malignant conditions such as eczema, psoriasis, periarthritis humeroscapularis, epicondylitis, knee arthrosis, hydradenitis, parotitis and panaritium and probably be associated with less acute and long-term side effects than similarly effective other treatments. Randomized clinical studies are required to find the optimal dosage which, at present, may be unnecessarily high. Since no adequate experimental studies have been performed nothing is known about the mechanisms of these therapeutic radiation

  4. Preparation of /sup 14/C-labelled AMP, ADP and ATP from adenine-8-/sup 14/C by using Brevibacterium ammoniagenes

    Energy Technology Data Exchange (ETDEWEB)

    Pande, V.N. (Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.)

    1985-04-01

    High radiochemical yields of /sup 14/C-labelled adenine nucleotides (AMP, 4.6%, ADP, 15.5% and ATP 59.5%) could be obtained by growing the cells of Brevibacterium ammoniagenes in the presence of /sup 14/C-adenine. The specific radioactivity of the adenine nucleotides almost reached that of /sup 14/C-adenine indicating negligible dilution of the label. The procedure is convenient and especially suited for commercial preparation of the radiolabelled nucleotides directly from labelled adenine. Preliminary results indicate that the organism could also be used for the preparation of radiolabelled guanine nucleotides.

  5. Therapeutic effects of low radiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Trott, K.R. (Dept. of Radiation Biology, St. Bartholomew' s Medical College, London (United Kingdom))

    1994-01-01

    This editorial explores the scientific basis of radiotherapy with doses of < 1 Gy for various non-malignant conditions, in particular dose-effect relationships, risk-benefit considerations and biological mechanisms. A review of the literature, particularly clinical and experimental reports published more than 50 years ago was conducted to clarify the following problems. 1. The dose-response relationships for the therapeutic effects on three groups of conditions: non-malignant skin disease, arthrosis and other painful degenerative joint disorders and anti-inflammatory radiotherapy; 2. risks after radiotherapy and after the best alternative treatments; 3. the biological mechanisms of the different therapeutic effects. Radiotherapy is very effective in all three groups of disease. Few dose-finding studies have been performed, all demonstrating that the optimal doses are considerable lower than the generally recommended doses. In different conditions, risk-benefit analysis of radiotherapy versus the best alternative treatment yields very different results: whereas radiotherapy for acute postpartum mastitis may not be justified any more, the risk-benefit ratio of radiotherapy of other conditions and particularly so in dermatology and some anti-inflammatory radiotherapy appears to be more favourable than the risk-benefit ratio of the best alternative treatments. Radiotherapy can be very effective treatment for various non-malignant conditions such as eczema, psoriasis, periarthritis humeroscapularis, epicondylitis, knee arthrosis, hydradenitis, parotitis and panaritium and probably be associated with less acute and long-term side effects than similarly effective other treatments. Randomized clinical studies are required to find the optimal dosage which, at present, may be unnecessarily high.

  6. Effects of polyacrylamide, biopolymer, and biochar on decomposition of soil organic matter and 14C-labeled plant residues as determined by enzyme activities

    Science.gov (United States)

    Mahmoud Awad, Yasser; Ok, Young Sik; Kuzyakov, Yakov

    2014-05-01

    Application of polymers for the improvement of aggregate structure and reduction of soil erosion may alter the availability and decomposition of plant residues. In this study, we assessed the effects of anionic polyacrylamide (PAM), synthesized biopolymer (BP), and biochar (BC) on the decomposition of 14C-labeled maize residue in sandy and sandy loam soils. Specifically, PAM and BP with or without 14C-labeled plant residue were applied at 400 kg ha-1, whereas BC was applied at 5000 kg ha-1, after which the soils were incubated for 80 days at 22 oC. Initially, plant residue decomposition was much higher in untreated sandy loam soil than in sandy soil. Nevertheless, the stimulating effects of BP and BC on the decomposition of plant residue were more pronounced in sandy soil, where it accounted for 13.4% and 23.4% of 14C input, respectively, whereas in sandy loam soil, the acceleration of plant residue decomposition by BP and BC did not exceed 2.6% and 14.1%, respectively, compared to untreated soil with plant residue. The stimulating effects of BP and BC on the decomposition of plant residue were confirmed based on activities of β-cellobiohydrolase, β-glucosidase, and chitinase in both soils. In contrast to BC and BP, PAM did not increase the decomposition of native or added C in both soils.

  7. Identification of the bound residue composition derived from 14C-labeled chlorsulfuron in soil by using LC-MS and isotope tracing method

    Institute of Scientific and Technical Information of China (English)

    YE Qing-fu; WU Jian-min; SUN Jin-he

    2004-01-01

    A new method for extracting the bound residue(BR) derived from 14C-labeled chlorsulfuron in soils was developed, and the technique of combining LC-MS with isotope tracing method was subsequently applied to identify the composition of the 14 C-BR in a loamy Fluvent derived from marine deposit. The results showed that the 14C-[2-amino-4-methoxyl-6-methyl-1,3,5]-triazine, 14 C-[ 2-amino-4-hydroxyl-6-methyl-1,3,5]-triazine and 14 C-chlorsulfuron parent compound constituted the main composition of the 14 C-BR derived from 14 C-labeled chlorsulfuron in the soil. The radioactive ratio of three compounds accounted for 39.8 %, 35.4 % and 17.9 % of total recovered radioactivity, respectively. However, a small amount(3.6% of total recovered radioactivity) of the complex of 14 C-[ 2-amino-4-hydroxyl-6-methyl-1,3,5 ]-triazine might have existed in the 14 C-BR in association with an unknown soil substrate. 2-chlorobenzenesulfonamide was also detected to be one of the components of the BR. The results could well explain the mechanism of phytotoxicity caused by the BR derived from chlorsulfuron in soil. In addition, the mechanism of BR formation in soil was also discussed in details.

  8. Research perspectives and role of lactose uptake rate revealed by its study using 14C-labelled lactose in whey fermentation.

    Science.gov (United States)

    Golfinopoulos, Aristidis; Kopsahelis, Nikolaos; Tsaousi, Konstantina; Koutinas, Athanasios A; Soupioni, Magdalini

    2011-03-01

    The present investigation examines the effect of pH, temperature and cell concentration on lactose uptake rate, in relation with kinetics of whey fermentation using kefir and determines the optimum conditions of these parameters. Lactose uptake rate was measured by adding (14)C-labelled lactose in whey. The results reveal the role of lactose uptake rate, being the main factor that affects the rate of fermentation, in contrast to the activity of the enzymes involved in lactose bioconversion process. Lactose uptake rate results discussion showed that mainly Ca(2+) is responsible for the reduced whey fermentation rate in comparison with fermentations using synthetic media containing lactose. Likewise, the results draw up perspectives on whey fermentation research to improve whey fermentation rate. Those perspectives are research to remove Ca(2+) from whey, the use of nano and microtubular biopolymers and promoters such as γ-alumina pellets and volcan foaming rock kissiris in order to accelerate whey fermentation. PMID:21232943

  9. Preparation of [14C]-labelled 1,2,3,4,6-penta-O-galloyl-β-D-glucose and related gallotannins

    International Nuclear Information System (INIS)

    [U-14C]-Labelled 1,2,3,4,6-penta-O-galloyl-β-D-glucose was prepared by photoassimilation of 14CO2 with leaves from staghorn sumac (Rhus typhina) in the presence of the herbicide glyphosate. Extracts of the plant material were partitioned against ethyl acetate and chromatographed on Sephadex LH-20, yielding a series of crude tri- to decagalloylglucoses. The pentagalloylclucose fraction among these was further pruified by HPLC to >99% purity and a specific radioactivity of 130 kBq (3.5 μCi) per μmol. The ratio of the radioactivities in the glucose and galloyl moieties, respectively, suggested a uniform labelling pattern of the product. (orig.)

  10. Lactose uptake rate measurements by 14C-labelled lactose reveals promotional activity of porous cellulose in whey fermentation by kefir yeast.

    Science.gov (United States)

    Golfinopoulos, Aristidis; Soupioni, Magdalini; Kopsahelis, Nikolaos; Tsaousi, Konstantina; Koutinas, Athanasios A

    2012-10-15

    Lactose uptake rate by kefir yeast, immobilized on tubular cellulose and gluten pellets during fermentation of lactose and whey, was monitored using (14)C-labelled lactose. Results illustrated that, in all cases, lactose uptake rate was strongly correlated with fermentation rate and the fermentation's kinetic parameters were improved by kefir yeast entrapped in tubular cellulose. As a result, twofold faster fermentations were achieved in comparison with kefir yeast immobilized on gluten. This is probably due to cluster and hydrogen bonds formation between cellulose and inhibitors, such as Ca(++) and generated lactic acid, by which they leave the liquid medium. The findings, regarding the promotional effect of cellulose, seem promising for application in industrial whey fermentations. PMID:23442646

  11. Aerobic biotransformation of 14C-labeled 8-2 telomer B alcohol by activated sludge from a domestic sewage treatment plant.

    Science.gov (United States)

    Wang, Ning; Szostek, Bogdan; Folsom, Patrick W; Sulecki, Lisa M; Capka, Vladimir; Buck, Robert C; Berti, William R; Gannon, John T

    2005-01-15

    This study investigated the biodegradation potential of 3-(14)C,1H,1H,2H,2H-perfluorodecanol [CF3(CF2)6(14)CF2CH2CH2OH, 14C-labeled 8-2 telomer B alcohol or 14C-labeled 8-2 TBA] by diluted activated sludge from a domestic wastewater treatment plant under aerobic conditions. After sample extraction with acetonitrile, biotransformation products were separated and quantified by LC/ARC (on-line liquid chromatography/accurate radioisotope counting) with a limit of quantification about 0.5% of the 14C counts applied to the test systems. Identification of biotransformation products was performed by quadrupole time-of-flight mass spectrometry. Three transformation products have been identified: CF3(CF2)6(14)CF2CH2COOH (8-2 saturated acid); CF3(CF2)6(14)CF=CHCOOH (8-2 unsaturated acid); and CF3(CF2)6(14)COOH (perfluorooctanoic acid, PFOA), representing 27, 6.0, and 2.1% of the initial 14C mass (14C counts applied) after 28 days, respectively. A transformation product, not yet reported in the literature, has also been observed and tentatively identified as CF3(CF2)6(14)CH2CH2COOH (2H,2H,3H,3H-perfluorodecanoic acid); it accounted for 2.3% of the mass balance after 28 days. The 2H,2H,3H,3H-perfluorodecanoic acid is likely a substrate for beta-oxidation, which represents one of the possible pathways for 8-2 telomer B alcohol degradation. The 8-2 saturated acid and 8-2 unsaturated acid cannot be directly used as substrates for beta-oxidation due to the proton deficiency in their beta-carbon (C3 carbon) and their further catabolism may be catalyzed by some other still unknown mechanisms. The 2H,2H,3H,3H-perfluorodecanoic acid may originate either from the major transformation product CF3(CF2)6(14)CF2CH2COOH or from other unidentified transformation products via multiple steps. Approximately 57% of the starting material remained unchanged after 28 days, likely due to its strong adsorption to the PTFE (poly(tetrafluoroethylene)) septa of the test vessels. No CF3(CF2)6(14)CF2COOH

  12. Intestinal absorbtion from therapeutic iron doses

    International Nuclear Information System (INIS)

    On a total of 105 persons with normal iron stores, iron depletion, and iron deficiency the intestinal absorption from therapeutic iron doses (100 mg Fe and 50 mg Fe as ferrous glycocoll sulphate) of a special galenic form was measured. The measurements were performed by means of a whole-body counter and preparations labelled with radio iron (59Fe). Mean values of absorption rates from 100 mg Fe in healthy males were 5.0% and in healthy females 5.6% whereas in latent iron deficiency and in iron deficiency anemia mean values of 10% and 13% were obtained, respectively. The maximum absorption rate of 20 to 25% is reached already in the late stage of latent iron deficiency. Advancing severeness of iron deficiency is not followed by an increase of iron absorption. Investigations an 21 persons showed no significant difference between absorption rates of the galenic preparations used when administered orally before or after breakfast, respectively. (orig.)

  13. Over-estimation of glucose-6-phosphatase activity in brain in vivo. Apparent difference in rates of [2-3H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with 14C-labeled products and incomplete recovery of 14C-labeled metabolites

    International Nuclear Information System (INIS)

    Significant dephosphorylation of glucose 6-phosphate due to glucose-6-phosphatase activity in rat brain in vivo was recently reported. The evidence was an apparent more rapid 3H than 14C loss from the glucose pool and faster [2-3H]glucose than [U-14C]glucose utilization following pulse labeling of the brain with [2-3H,U-14C]glucose. Radiochemical purity of the glucose and quantitative recovery of the labeled products of glucose metabolism isolated from the brain were obviously essential requirements of their study, but no evidence for purity and recovery was provided. When we repeated these experiments with the described isolation procedures, we replicated the results, but found that: 1) the precursor glucose pool contained detritiated, 14C-labeled contaminants arising from glucose metabolism, particularly 2-pyrrolidone-5-carboxylic acid derived from [14C]glutamine; 2) [14C]glucose metabolite were not quantitatively recovered; 3) the procedure used to isolate the glucose itself produced detritiated, 14C-labeled derivatives of [2-3H,U-14C]glucose. These deficiencies in the isolation procedures could fully account for the observations that were interpreted as evidence of significant glucose 6-phosphate dephosphorylation by glucose-6-phosphatase activity. When glucose was isolated by more rigorous procedures and its purity verified in the present studies, no evidence for such activity in rat brain was found

  14. Degradation of 14C labelled Benzo[a]pyrene by a PAH-adapted mixed bacterial culture in the presence of an alkylpolyglycoside-surfactant

    International Nuclear Information System (INIS)

    The biodegradation of the five ring PAH benzo[a]pyrene (BaP) is assumed to be limited by the low water solubility of this compound. A mixed culture of microorganisms - isolated from a PAH-contaminated soil - was able to degrade 14C labelled BaP in mineral medium by co-metabolism with phenanthrene, fluoranthene, anthracene and pyrene as sources of carbon and energy. The mineralisation of these compounds to low levels resulted in an inhibition of the degradation of BaP. After the new addition of the four PAH compounds to the culture medium the mineralisation of BaP started again. A non-ionic surfactant of the alkylpolyglycoside type (Plantacare 2000 UP) increased the concentration of BaP in the culture medium because of solubilization. At high Plantacare concentrations, the degradation of BaP was completely inhibited above the critical micelle concentration (cms). The degradation of the three and four ring PAHs was also inhibited. If the surfactant was metabolised to concentrations below the cmc, an increase of mineralisation of BaP could occur up to 24% in 384 days. (orig.)

  15. Study of lignin biotransformation by Aspergillus fumigatus and white-rot fungi using 14C-labeled and unlabeled kraft lignins

    International Nuclear Information System (INIS)

    The biodegradation of lignin by fungi was studied in shake flasks using 14C-labeled kraft lignin and in a deep-tank fermentor using unlabeled kraft lignin. Among the fungi screened, A. fumigatus - isolated in our laboratories - was most potent in lignin biotransformation. Dialysis-type fermentation, designed to study possible accumulation of low MW lignin-derived products, showed no such accumulation. Recalcitrant carbohydrates like microcrystalline cellulose supported higher lignolytic activity than easily metabolized carbohydrates like cellobiose. An assay developed to distinguish between CO2 evolved from lignin and carbohydrate substrates demonstrated no stoichiometric correlation between the metabolism of the two cosubstrates. The submerged fermentations with unlabeled liqnin are difficult to monitor since chemical assays do not give accurate and true results. Lignolytic efficiencies that allowed monitoring of such fermentations were defined. Degraded lignins were clearly superior to C. versicolor in all aspects of lignin degradation; A fumigatus brought about substantial demethoxylation and dehydroxylation, whereas C. versicolor degraded lignins closely resembled undegraded kraft lignin. There was a good agreement among the different indices of lignin degradation, namely, 14CO evolution, OCH3 loss, OH loss, and monomer and dimer yield after permanganate oxidation

  16. Studies on the percutaneous absorption of /sup 14/C-labelled Flurbiprofen, 3. Whole body autoradiography of rats and guinea-pigs

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, Soshichi; Sakai, Takeo; Hayakawa, Toru (Nihon Univ., Tokyo. Coll. of Agriculture and Veterinary Medicine)

    1983-03-01

    Whole body autoradiography was carried out to clarify and compare the distribution of /sup 14/C-labelled Flurbiprofen which was applied to the skin as an ointment in rats and guinea-pigs. Both in rats and guinea-pigs almost the same autoradiogram was gained. The radioactivity was strongest at the skin area inspite of the time elapse, showing that the drug was fixed in the site of skin applied. In other parts of the body, however, it was small except the kidney and intestine. It seemed that the absorption of the drug was a little although the migration of the drug into the blood circulation is fast at the beginning as was shown in pigs previously. A stronger radioactivity in the kidney and intestine might indicate that a main pathway of excretion of this drug was through those two organs. Absorption, distribution and excretion of the drug were not different between rats and guinea-pigs, similar to those observed in pigs.

  17. Using Position-Specific 13C and 14C Labeling and 13C-PLFA Analysis to Assess Microbial Transformations of Free Versus Sorbed Alanine

    Science.gov (United States)

    Apostel, C.; Herschbach, J.; Bore, E. K.; Kuzyakov, Y.; Dippold, M. A.

    2015-12-01

    Sorption of charged or partially charged low molecular weight organic substances (LMWOS) to soil mineral surfaces delays microbial uptake and therefore mineralization of LMWOS to CO2, as well as all other biochemical transformations. We used position-specific labeling, a tool of isotope applications novel to soil sciences, to compare the transformation mechanisms of sorbed and non-sorbed alanine in soil. Alanine as an amino acid links C- and N-cycles in soil and therefore is a model substance for the pool of LMWOS. To assess transformations of sorbed alanine, we added position-specific and uniformly 13C and 14C labeled alanine tracer to soil that had previously been sterilized by γ-radiation. The labeled soil was added to non-sterilized soil from the same site and incubated. Soil labeled with the same tracers without previous sorption was prepared and incubated as well. We captured the respired CO2 and determined its 14C-activity at increasing time intervals. The incorporation of 14C into microbial biomass was determined by chloroform fumigation extraction (CFE), and utilization of individual C positions by distinct microbial groups was evaluated by 13C-phospholipid fatty acid analysis (PLFA). A dual peak in the respired CO2 revealed two sorption mechanisms. To compare the fate of individual C atoms independent of their concentration and pool size in soil, we applied the divergence index (DI). The DI reveals the convergent or divergent behavior of C from individual molecule positions during microbial utilization. Alanine C-1 position was mainly oxidized to CO2, while its C-2 and C-3 were preferentially incorporated in microbial biomass and PLFA. This indicates that sorption by the COOH group does not protect this group from preferential oxidation. Microbial metabolism was determinative for the preferential oxidation of individual molecule positions. The use of position-specific labeling revealed mechanisms and kinetics of microbial utilization of sorbed and non

  18. Translocation of 14C-Labelled Substances and 32PO4 in Mistletoe-Infected and Uninfected Conifers and Dicotyledonous Trees

    International Nuclear Information System (INIS)

    Translocation studies, employing autoradiographic techniques, were conducted on eight dwarf mistletoe (Arceuthobium) infected hosts and eight green mistletoe (Phoradendron) infected hosts and uninfected hosts. These studies were conducted in the field at different seasons of the year over a 4-yr period. It was necessary to overcome the problem of pseudo-autoradiographs, especially prominent with conifers. These were overcome by using special film materials, such as Saran Wrap; this film excluded about 50% of the beta radiation. Translocation was studied using labelled substances applied to the host foliage, bark, wood, and mistletoe shoots. Labelled substances employed were 14CO2 (applied to host foliage and mistletoe shoots), 14C-labelled herbicides and 32PO4. Phloem mobile substances translocated from the hosts into infecting dwarf mistletoes but not into green mistletoes. When the host branches were defoliated, phloem mobile Substances moved into them during the growing season. When dormant, very little transport into defoliated branches occurred, except when they were infected with dwarf mistletoes; in the latter situation, import was considerable into such branches and also into the infecting mistletoes. Phloem mobile substances in dwarf mistletoes migrated always in an apical direction, accumulating in the nodes, flowers, and fruit. In no instance was there any evidence of any basipetal transport (labelled assimilates 2,4-dichlorophenoxyacetic acid, 2, 4, 5-trichlorophenoxyacetic acid, 3-amino-1, 2,4-triazole, 2-chloro-4-ethylamino-6-isopropylamino-1, 3, 5-triazine, 1,1'-dimethyl-4,4',-bipyridylium-2A, urea and 32PO4). In contrast to this, the green mistletoes moved substances within them in much the same manner as normal green plants; however, phloem mobile substances did not migrate significantly out of the endophytic system into the hosts, even when the host branches were defoliated. Xylem application was the most effective method of introducing all

  19. Influence of alternating soil drying and wetting on the desorption and distribution of aged 14C-labeled pesticide residues in soil organic fractions

    Science.gov (United States)

    Jablonowski, N. D.; Mucha, M.; Thiele, B.; Hofmann, D.; Burauel, P.

    2012-04-01

    A laboratory experiment was conducted to evaluate the effect of alternating soil drying and wetting on the release of aged 14C-labeled pesticide residues and their distribution in soil organic fractions (humic acids, fulvic acids, and humin substances). The used soils (gleyic cambisol; Corg 1.2%, pH 7.2) were obtained from the upper soil layer of two individual outdoor lysimeter studies containing either environmentally long-term aged 14C residues of the herbicide ethidimuron (ETD; 0-10 cm depth; time of aging: 9 years) or methabenzthiazuron (MBT; 0-30 cm depth; time of aging: 17 years). Triplicate soil samples (10 g dry soil equivalents) were (A=dry/wet) previously dried (45° C) or (B=wet/wet) directly mixed with pure water (1+2, w:w), shaken (150 rpm, 1 h), and centrifuged (~2000 g). The resulting supernatant was removed, filtered (0.45 μm) and subjected to 14C activity analysis via liquid scintillation counter (LSC), dissolved organic carbon (DOC) analysis, and LC-MS-MS analysis. This extraction procedure was repeated 15 individual times, for both setups (A) and (B). To determine the distribution of the aged 14C labelled pesticide residues in the soil organic matter fractions, the soil samples were subject to humic and fulvic acids fractionations at cycles 0, 4, 10, and 15. The residual pesticide 14C activity associated with the humic, fulvic, and humin substances (organic fraction remaining in the soil) fractions was determined via LSC. The water-extracted residual 14C activity was significantly higher in the extracts of the dry/wet, compared to the wet/wet soil samples for both pesticides. The total extracted 14C activity in the dry/wet soil extracts accounted for 51.0% (ETD) and 15.4% (MBT) in contrast to 19.0% (ETD) and 4.7% (MBT) in the wet/wet extracts after 15 water extractions. LC-MS-MS analysis revealed the parent compound ETD 27.9 μg kg-1 soil (dry/wet) and 10.7 μg kg-1 soil (wet/wet), accounting for 3.45 and 1.35% of total parent compound

  20. A balance study of /sup 14/C-labelled /sup 3/H-imidazo(4,5-f)quinolin-2-amines (IQ and MeIQ) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sjoedin, P.; Jaegerstad, M.

    1984-03-01

    The absorption and excretion of /sup 14/C-labelled 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ) were studied in rats of both sexes. The excretion was rapid and within 24 hr more than 90% of the radioactivity had left the rats. After 72 hr the faecal excretion of both compounds was approximately 45-65% and the corresponding excretion via the urine amounted to 37-49%. Only 1-2% was left in the carcasses and less than 0.2% was found in the expired air. About 70% of the IQ and 80% of the MeIQ was found in the bile fluid in a separate 24-hr study. The two compounds had different biliary excretion patterns and the mutagenicity of the bile correlated closely with the excretion of radioactivity.

  1. Predictive Models for Maximum Recommended Therapeutic Dose of Antiretroviral Drugs

    Directory of Open Access Journals (Sweden)

    Michael Lee Branham

    2012-01-01

    Full Text Available A novel method for predicting maximum recommended therapeutic dose (MRTD is presented using quantitative structure property relationships (QSPRs and artificial neural networks (ANNs. MRTD data of 31 structurally diverse Antiretroviral drugs (ARVs were collected from FDA MRTD Database or package inserts. Molecular property descriptors of each compound, that is, molecular mass, aqueous solubility, lipophilicity, biotransformation half life, oxidation half life, and biodegradation probability were calculated from their SMILES codes. A training set (=23 was used to construct multiple linear regression and back propagation neural network models. The models were validated using an external test set (=8 which demonstrated that MRTD values may be predicted with reasonable accuracy. Model predictability was described by root mean squared errors (RMSEs, Kendall's correlation coefficients (tau, P-values, and Bland Altman plots for method comparisons. MRTD was predicted by a 6-3-1 neural network model (RMSE=13.67, tau=0.643, =0.035 more accurately than by the multiple linear regression (RMSE=27.27, tau=0.714, =0.019 model. Both models illustrated a moderate correlation between aqueous solubility of antiretroviral drugs and maximum therapeutic dose. MRTD prediction may assist in the design of safer, more effective treatments for HIV infection.

  2. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

    Directory of Open Access Journals (Sweden)

    Judge Bryan S

    2011-03-01

    Full Text Available Abstract Background Acetaminophen-cysteine adducts (APAP-CYS are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated. Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20 nmol/ml, Trial 2- 0.1 (0.09 nmol/ml and Trial 3- 0.3 (0.12 nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml. No subject had detectable APAP

  3. Profound opiate toxicity in gastroparesis following therapeutic dose.

    Science.gov (United States)

    Craven, Henry; Iftikhar, Hina; Bhatnagar, Pallav

    2016-01-01

    Gastroparesis is defined by the presence of delayed gastric emptying without mechanical obstruction. Patients may present with severe discomfort that can mimic an acute abdomen including abdominal pain, vomiting, nausea, bloating, fullness and early satiety. The prevalence of gastroparesis is estimated at 24 per 100 000 and women are more commonly affected than men. It is associated with a number of conditions including diabetes, Parkinson's disease, multiple sclerosis, previous abdominal surgeries and connective tissue disorders, including scleroderma and Ehlers-Danlos syndrome. Drugs known to prolong gastric transit time, such as opiates, have been shown to exacerbate symptoms. We report a case of a 20-year-old woman with Ehlers-Danlos syndrome who developed respiratory depression after being administered a therapeutic dose of morphine. This occurred due to opiate toxicity confounded by gastroparesis. The patient required further support from intensive care until she recovered, and eventually underwent a gastric pacing procedure for symptomatic relief. PMID:27147632

  4. IV. Study of the stability of 14C-labelled coumaphos in the presence of sediment, an acidic buffer and a bacteriostatic agent in model dipping vats under outdoor conditions

    International Nuclear Information System (INIS)

    The effect of the addition of sediment, a buffering agent (superphosphate fertilizer) and a bacteriostat (copper sulphate) on the stability of 14C-labelled coumaphos in suspension in model dipping vats was studied for a period of 180 days under outdoor conditions. At the end of this period the highest proportion of the initial radioactivity (36%) was in the vats containing coumaphos suspension with no additives and the lowest (10%) in the vats in which the bacteriostat and sediment were added to coumaphos suspension. Recovery was lowered in all vats to which sediment or the bacteriostat had been added. In the presence of sediment or the bacteriostat addition of the buffering agent did not have any affect on the levels of radioactivity after 180 days. Thus, the addition of superphosphate to coumaphos suspension containing bacteriostat reduced the radioactivity from 26% to 23% of the initial amount. The radioactivity level was 10% in the suspension to which sediment had been added and 12 % to which both sediment and superphosphate were added. (author)

  5. Cone-beam computed tomography imaging: therapeutic staff dose during chemoembolisation procedure

    International Nuclear Information System (INIS)

    Cone-beam computed tomography (CBCT) imaging is an important requirement to perform real-time therapeutic image-guided procedures on patients. The purpose of this study is to estimate the personal-dose-equivalent and annual-personal-dose from CBCT imaging during transarterial chemoembolisation (TACE). Therapeutic staff doses (therapeutic and assistant physician) were collected during 200 patient (65  ±  15 years, range: 40–86) CBCT examinations over six months. Absorbed doses were assessed using thermo-luminescent dosimeters during patient hepatic TACE therapy. We estimated personal-dose-equivalent (PDE) and annual-personal-dose (APD) from absorbed dose based on international atomic energy agency protocol. APD for therapeutic procedure was calculated (therapeutic physician: 5.6 mSv; assistant physician: 5.08 mSv) based on institutional work load. Regarding PDE, the hands of the staff members received a greater dose compared to other anatomical locations (therapeutic physician: 56 mSv, 72 mSv; assistant physician: 12 mSv, 14 mSv). Annual radiation doses to the eyes and hands of the staff members were lower compared to the prescribed limits by the International Commission on Radiological Protection (ICRP). PDE and APD of both therapeutic staff members were within the recommended ICRP-103 annual limit. Dose to the assistant physician was lower than the dose to the therapeutic physician during imaging. Annual radiation doses to eye-lenses and hands of both staff members were lower than prescribed limits. (paper)

  6. Specification of absorbed dose for reporting a therapeutic irradiation

    International Nuclear Information System (INIS)

    The problem of dose specification in external beam therapy with photons and electrons has been dealt with in ICRU Report 29 (1978). This problem arises from the fact that the absorbed dose distribution is usually not uniform in the target volume and that for the purpose of treatment reporting a nominal absorbed dose - which will be called target absorbed dose - has to be selected. When comparing the clinical results obtained between radiotherapy centres, the differences in the reported target absorbed doses which can be introduced by differences in the methods of dose specification often are much larger than the differences related to the dosimetric procedures themselves. This shows the importance of the problem. In this paper, some definitions of terms and concepts currently used in radiotherapy are first recalled: tumour volume, target volume, treatment volume, etc. These definitions have been proposed in ICRU Report 29 for photon and electron beams; they can be extended to any kind of irradiation. For external beam therapy with photons and electrons, the target absorbed dose is defined as the absorbed dose at selected point(s) (specification point(s)) having a meaningful relation to the target volume and/or the irradiation beams. Examples are discussed for typical cases. As far as interstitial and intracavitary therapy is concerned, the problem is more complex and no recommendations have so far been made by the ICRU Commission. A major difficulty arises from the sharp dose gradient as a function of the distance to the sources. The particular case of the treatment of cervix carcinoma is considered and some possible methods of specification are discussed: (1) the indication of the sources (in adequate units) and the duration of the application, (2) the absorbed doses at selected reference points (bladder, rectum, bony structures) and (3) the description of the tissue volume (height, width, thickness) encompassed by a given isodose surface (60Gy). (author)

  7. Therapeutic Advantages of Treatment of High-Dose Curcumin in the Ovariectomized Rat

    OpenAIRE

    Cho, Dae-Chul; Jung, Hyun-Sik; Kim, Kyoung-Tae; Jeon, Younghoon; Sung, Joo-Kyung; Hwang, Jeong-Hyun

    2013-01-01

    Objective Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats. Methods Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed...

  8. Methodology to administer therapeutic dose of I-131

    International Nuclear Information System (INIS)

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment of the thyroid cancer with Iodine-131, as well as the use of citric fruits to stimulate the salivation, the post-dose administration of liquids to accelerate the gastric emptying avoiding the secondary effects as the vomit is included. (Author)

  9. Measurement of dose distributions using film in therapeutic electron beams

    International Nuclear Information System (INIS)

    The feasibility of using film dosimetry data as the input data for patient treatment planning was evaluated. The central-axis depth dose and the off-axis ratios obtained from film measurements in a solid phantom were compared with those of ion-chamber measurements in water. Two techniques were used to generate isodose distributions. The first technique used only the film data, i.e., the central-axis depth dose and the off-axis ratios used for the reconstruction were determined from the film optical density (corrected for film nonlinearity). In the second technique, the central-axis depth dose measured by an ion chamber in a water phantom was combined with the off-axis ratios measured using film in the ''solid water'' phantom. The resulting isodose distributions from both techniques were compared with the ion-chamber measurements in water for 7-, 12-, and 18-MeV electrons, and the second technique showed better agreement with the ion-chamber measurements than did the first technique. The differences were within a clinically acceptable range

  10. Therapeutic termination of second trimester pregnancies with low dose misoprostol

    International Nuclear Information System (INIS)

    To determine the effectiveness of 50 micro g misoprostol for midtrimester termination of pregnancies. The study subjects were 54 pregnant women admitted during the 2nd trimester (14-26 weeks) of gestation, willing or requiring termination of pregnancy. Those patients were included in the study who were admitted with closed cervical os, either had intrauterine death, fetal anomaly, medical disorder (hypertension or diabetes) or history of previous ceasrean section. Cases of placenta previa, acute asthma, glaucoma, cardiac diseases and allergy to prostaglandins were excluded. Each patient received 50 micro g misoprostol intravaginally. Maximum 4 doses were given at 4 hours interval and state of cervical os was assessed by vaginal examination before insertion of next dose or at the onset of uterine contractions. After 4 doses of misoprostol, patients were kept under observation and watched for uterine contractions to start or for expulsion of products. Syntocinon infusion was started to augment labour where products of conception failed to expel out inspite of open os. Outcome measures include success rate of termination within 12, 24, 36 and 48 hours, mean induction - abortion time interval and maternal side effects. Results: The success rate of termination within 12, 24, 36 and 48 hours were 27.7%, 83.3%, 94.4% and 96.3% respectively. Mean induction to abortion time interval, in case of abortion within 48 hours, was found to be 18.9 +- 11.58 (range 4-48 hours). Dead fetuses were aborted earlier than alive fetuses. The mean induction abortion time interval was 17.01+-8.7 hours in dead and 23.4 +- 15.9 hours in alive fetuses (t -value:1.9, p: 0.05). Two patients failed to deliver within 48 hours of induction. Two patients suffered from febrile illness. Vaginal administration of 50 micro g misoprostol every 4 hourly is an effective and safe agent for ripening of cervix and convenient way of inducing abortion during 2nd trimester of pregnancy in a women either with

  11. Simultaneous measurements of absorbed dose and linear energy transfer in therapeutic proton beams

    Science.gov (United States)

    Granville, Dal A.; Sahoo, Narayan; Sawakuchi, Gabriel O.

    2016-02-01

    The biological response resulting from proton therapy depends on both the absorbed dose in the irradiated tissue and the linear energy transfer (LET) of the beam. Currently, optimization of proton therapy treatment plans is based only on absorbed dose. However, recent advances in proton therapy delivery have made it possible to vary the LET distribution for potential therapeutic gain, leading to investigations of using LET as an additional parameter in plan optimization. Having a method to measure and verify both absorbed dose and LET as part of a quality assurance program would be ideal for the safe delivery of such plans. Here we demonstrated the potential of an optically stimulated luminescence (OSL) technique to simultaneously measure absorbed dose and LET. We calibrated the ratio of ultraviolet (UV) to blue emission intensities from Al2O3:C OSL detectors as a function of LET to facilitate LET measurements. We also calibrated the intensity of the blue OSL emission for absorbed dose measurements and introduced a technique to correct for the LET-dependent dose response of OSL detectors exposed to therapeutic proton beams. We demonstrated the potential of our OSL technique by using it to measure LET and absorbed dose under new irradiation conditions, including patient-specific proton therapy treatment plans. In the beams investigated, we found the OSL technique to measure dose-weighted LET within 7.9% of Monte Carlo-simulated values and absorbed dose within 2.5% of ionization chamber measurements.

  12. Enhanced therapeutic tumour dose of /sup 131/I-MIBG by accelerated diuresis

    Energy Technology Data Exchange (ETDEWEB)

    Darte, L.; Tennvall, J.

    1988-10-01

    Different biokinetics of intravenously (i.v.) administered /sup 131/I-MIBG in the same patient, a child with abdominal neuroblastoma, is demonstrated with and without accelerated elimination by means of hyperhydration. By hyperhydration it was possible to increase the estimated tumour dose by a factor of 2.1 without affecting the whole body dose. The present results indicate that, if accelerated diuresis is implemented, higher radioactivity of /sup 131/I-MIBG can be administered and thereby an increased therapeutic tumour dose achieved.

  13. Enhanced therapeutic tumour dose of 131I-MIBG by accelerated diuresis

    International Nuclear Information System (INIS)

    Different biokinetics of intravenously (i.v.) administered 131I-MIBG in the same patient, a child with abdominal neuroblastoma, is demonstrated with and without accelerated elimination by means of hyperhydration. By hyperhydration it was possible to increase the estimated tumour dose by a factor of 2.1 without affecting the whole body dose. The present results indicate that, if accelerated diuresis is implemented, higher radioactivity of 131I-MIBG can be administered and thereby an increased therapeutic tumour dose achieved. (orig.)

  14. Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription

    NARCIS (Netherlands)

    Hoffmann, A.L.; Huizenga, H.; Kaanders, J.H.A.M.

    2013-01-01

    BACKGROUND: In current practice, patients scheduled for radiotherapy are treated according to 'rigid' protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess

  15. Required therapeutic dose of 131I for thyroid ablation after surgery for differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Full text of publication follows. After operation for carcinoma of the thyroid gland a lot of patients are treated with radioactive iodine for ablation of the residual thyroid parenchyma. Aim: to determine the appropriate dose of radioactive iodine for ablation of the residual thyroid parenchyma in patients operated for differentiated thyroid carcinoma. Materials and methods: the study includes 316 patients who underwent a whole-body scan (WBS) scintigraphy with 131I. From 2009 to 2012 year 632 images were taken. Patients range from 21 to 78 years old. The scan was performed on a dual-headed gamma camera Siemens after an oral reception of a diagnostic dose 131I (2 mCi). The remnants of thyroid parenchyma were registered in 67 of the patients. 39 patients with registered remnants of thyroid parenchyma and slightly elevated thyroglobulin (TG) values who took therapeutic dose 131I (80-100 mCi) underwent a WBS scintigraphy with 131I and did not display remnants of thyroid parenchyma or extra thyroid accumulation of the radio nucleotide. 23 patients with several remnants of thyroid parenchyma and elevated values of TG who underwent a WBS scintigraphy with 131I eight to ten months after reception of the first dose therapeutic iodine (80-100 mCi) displayed persisting remnants of thyroid parenchyma. They were treated with a second dose of 131I (50-100 mCi). In 5 patients with high values of TG besides the thyroid remnants 3 of the patients displayed an extra thyroid accumulation in the lungs and 2 of them displayed an extra-thyroid fixation in the thoracic vertebras in addition to the fixation in the lungs. These 5 patients were treated twice with 131I, but still displayed the remnants of thyroid parenchyma and extra thyroid fixation. That group was treated with a third dose of 131I (30-50 mCi) and no remnants of thyroid parenchyma and extra-thyroid fixation of the radio nucleotide were visualized on the control WBS scintigraphy. Conclusion: in the majority of the patients

  16. Efficient production of therapeutic doses of [131I]-metaiodobenzylguanidine for clinical use

    International Nuclear Information System (INIS)

    [131I]-metaiodobenzylguanidine (mIBG) is a known radiopharmaceutical used for the treatment of neuroendocrine tumors. The development of therapeutic [131I]-mIBG doses at production level is highly challenging due to rapid product degradation and high radiation exposures to the production plant personnel. In the present work, a working module for the production of 10 doses (100 mCi each) in a single operation was developed following copper (I) assisted isotope exchange. The labeled product complies with the pharmaceutical specifications suitable for in-vivo patient use.

  17. Efficient production of therapeutic doses of [{sup 131}I]-metaiodobenzylguanidine for clinical use

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakar, G.; Mathur, Anupam; Shunmugam, G.; Teje, Y.D.; Sachdev, S.S. [Radiopharmaceuticals Program, Board of Radiation and Isotope Technology (BRIT), Sec. 20, Vashi, Navi Mumbai 400705 (India); Sivaprasad, N., E-mail: drnsivaprasad@rediffmail.co [Radiopharmaceuticals Program, Board of Radiation and Isotope Technology (BRIT), Sec. 20, Vashi, Navi Mumbai 400705 (India)

    2011-01-15

    [{sup 131}I]-metaiodobenzylguanidine (mIBG) is a known radiopharmaceutical used for the treatment of neuroendocrine tumors. The development of therapeutic [{sup 131}I]-mIBG doses at production level is highly challenging due to rapid product degradation and high radiation exposures to the production plant personnel. In the present work, a working module for the production of 10 doses (100 mCi each) in a single operation was developed following copper (I) assisted isotope exchange. The labeled product complies with the pharmaceutical specifications suitable for in-vivo patient use.

  18. Dosimetric evaluation of sucrose and granulated cane sugar in the therapeutic dose range

    International Nuclear Information System (INIS)

    Granulated cane sugar has been used as a dosimetric material to report dose in high dose accidental irradiations. The purpose of this study was to assess whether clinical dosimetry is also plausible with such a commonly available material. The behavior of cane sugar was explored with respect to therapeutically relevant radiation quantities (dose, dose rate) and qualities (energy, radiation type) as well as under different temperature conditions. The stability of the signal postirradiation was also measured. Absorbed dose was measured by spectrophotometric readout of a ferrous ammonium sulfate xylenol orange (FX)-sugar solution in 10 cm path length cells. A visible color change was produced as a function of dose when the irradiated sugar samples were dissolved in FX solution (10% dilution by mass). A comparison of the optical absorbance spectra and dose response of cane sugar with analytical grade sucrose was done to establish a benchmark standard from which subsequent dosimetry measurements can be validated. The response of the sugar dosimeter read at 590 nm was found to be linear over the dose range of 100-2000 cGy, independent of energy (6-18 MV) and of the average dose rate (100-500 cGy/min). The readout of sugar samples irradiated with mixed photon and electron fields was also shown to be independent of radiation type (photons and electrons). Sugar temperature (20-40 degree sign C) during irradiation did not affect dose estimates, making it a promising dosimeter for in vivo dosimetry, particularly in cases where the dosimeter must remain in contact with the patient for an extended period of time. Sugar can be used as an integrating dosimeter, since it exhibits no fractionation effects. Granulated cane sugar is cost effective, safe, soft tissue equivalent, and can be used under various experimental conditions, making it a suitable dosimeter for some radiotherapy applications.

  19. Acute pancreatitis related to therapeutic dosing with colchicine: a case report

    Directory of Open Access Journals (Sweden)

    Ting Joseph

    2007-08-01

    Full Text Available Abstract Background Colchicine is used in the treatment and prophylaxis of gout. It possesses a narrow therapeutic window, frequently resulting in dose-limiting gastrointestinal side-effects such as diarrhoea and emesis. As colchicine is a cellular anti-mitotic agent, the most serious effects include myelosuppression, myoneuropathy and multiple organ failure. This occurs with intentional overdose or with therapeutic dosing in patients with reduced clearance of colchicine due to pre-existing renal or hepatic impairment. Acute pancreatitis has rarely been reported, and only in association with severe colchicine overdose accompanied by multi-organ failure. Case presentation We report a case of acute pancreatitis without other organ toxicity related to recent commencement of colchicine for acute gout, occurring in an elderly male with pre-existing renal impairment. Conclusion 1 Colchicine should be used with care in elderly patients or patients with impaired renal function. 2 Aside from myelosuppression, myoneuropathy and multiple organ failure, colchicine may now be associated with acute pancreatitis even with therapeutic dosing; this has not previously being reported.

  20. Psychosis with paranoid delusions after a therapeutic dose of mefloquine: a case report

    Directory of Open Access Journals (Sweden)

    Browning Joseph

    2006-08-01

    Full Text Available Abstract Background Convenient once-a-week dosing has made mefloquine a popular choice as malaria prophylaxis for travel to countries with chloroquine-resistant malaria. However, the increased use of mefloquine over the past decade has resulted in reports of rare, but severe, neuropsychiatric adverse reactions, such as anxiety, depression, hallucinations and psychosis. A direct causality between mefloquine and severe reactions among travelers has been partly confounded by factors associated with foreign travel and, in the case of therapeutic doses of mefloquine, the central nervous system manifestations of Plasmodium infection itself. The present case provides a unique natural history of mefloquine-induced neuropsychiatric toxicity and revisits its dose-dependent nature. Case presentation This report describes an acute exacerbation of neuropsychiatric symptoms after an unwarranted therapeutic dose (1250 mg of mefloquine in a 37-year-old male previously on a once-a-week prophylactic regimen. Neuropsychiatric symptoms began as dizziness and insomnia of several days duration, which was followed by one week of escalating anxiety and subtle alterations in behaviour. The patient's anxiety culminated into a panic episode with profound sympathetic activation. One week later, he was hospitalized after developing frank psychosis with psychomotor agitation and paranoid delusions. His psychosis remitted with low-dose quetiapine. Conclusion This report suggests that an overt mefloquine-induced psychosis can be preceded by a prodromal phase of moderate symptoms such as dizziness, insomnia, and generalized anxiety. It is important that physicians advise patients taking mefloquine prophylaxis and their relatives to recognize such symptoms, especially when they are accompanied by abrupt, but subtle, changes in behaviour. Patients with a history of psychiatric illness, however minor, may be at increased risk for a mefloquine-induced neuropsychiatric toxicity

  1. Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study.

    Science.gov (United States)

    Wali, Bushra; Ishrat, Tauheed; Won, Soonmi; Stein, Donald G; Sayeed, Iqbal

    2014-02-01

    Currently, the only approved treatment for ischaemic stroke is tissue plasminogen activator, a clot-buster. This treatment can have dangerous consequences if not given within the first 4 h after stroke. Our group and others have shown progesterone to be beneficial in preclinical studies of stroke, but a progesterone dose-response and time-window study is lacking. We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance. For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion, and subcutaneous injections at 6 h and then once every 24 h for 7 days. For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke. Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume. Both 8 and 16 mg/kg doses of progesterone produced attenuation of infarct volume compared with the placebo, and improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests. In the time-window study, the progesterone group exhibited substantial neuroprotection as late as 6 h after stroke onset. Compared with placebo, progesterone showed a significant reduction in infarct size with 3- and 6-h delays. Moderate doses (8 and 16 mg/kg) of progesterone reduced infarct size and improved functional deficits in our clinically relevant model of stroke. The 8 mg/kg dose was optimal in improving motor, sensory and memory function, and this effect was observed over a large therapeutic time window. Progesterone shows promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischaemic stroke. PMID:24374329

  2. Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization

    Energy Technology Data Exchange (ETDEWEB)

    Gay, H A [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Allison, R R [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Downie, G H [Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Mota, H C [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Austerlitz, C [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Jenkins, T [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Sibata, C H [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States)

    2007-06-07

    A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed.

  3. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  4. Methodology for management of therapeutic dose of I-131; Metodologia para administrar dosis terapeutica de I-131

    Energy Technology Data Exchange (ETDEWEB)

    Basteris M, J.; Gomez D, R. [Universidad Autonoma de Yucatan, Facultad de Medicina, Merida, Yucatan (Mexico)

    2007-07-01

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment previously described with a therapeutic dose bigger than ablative of Iodine 131, as well as the use of citric fruits to stimulate the salivation, the administration of liquid post-dose is included to accelerate the gastric emptying avoiding the secondary effects as the vomit. (Author)

  5. Evaluation of human pharmacokinetics, therapeutic dose and exposure predictions using marketed oral drugs.

    Science.gov (United States)

    McGinnity, D F; Collington, J; Austin, R P; Riley, R J

    2007-06-01

    In this article approaches to predict human pharmacokinetics (PK) are discussed and the capability of the exemplified methodologies to estimate individual PK parameters and therapeutic dose for a set of marketed oral drugs has been assessed. For a set of 63 drugs where the minimum efficacious concentration (MEC) and human PK were known, the clinical dose was shown to be well predicted or in some cases over-estimated using a simple one-compartment oral PK model. For a subset of these drugs, in vitro potency against the primary human targets was gathered, and compared to the observed MEC. When corrected for plasma protein binding, the MEC of the majority of compounds was GFR. For approximately 90% of compounds studied, the predicted CL using in vitro-in vivo (IVIV) extrapolation together with a CL(renal) estimate, where appropriate, was within 2-fold of that observed clinically. Encouragingly volume of distribution at steady state (V(ss)) estimated in preclinical species (rat and dog) when corrected for plasma protein binding, predicted human V(ss) successfully on the majority of occasions--73% of compounds within 2-fold. In this laboratory, absorption estimated from oral rat PK studies was lower than the observed human absorption for most drugs, even when solubility and permeability appeared not to be limiting. Preliminary data indicate absorption in the dog may be more representative of human for compounds absorbed via the transcellular pathway. Using predicted PK and MEC values estimated from in vitro potency assays there was a good correlation between predicted and observed dose. This analysis suggests that for oral therapies, human PK parameters and clinical dose can be estimated from a consideration of data obtained from in vitro screens using human derived material and in vivo animal studies. The benefits and limitations of this holistic approach to PK and dose prediction within the drug discovery process are exemplified and discussed.

  6. Fate of 14C-Labelled Triazine Herbicides in Plants

    International Nuclear Information System (INIS)

    The resistance of certain plant species to triazines is referred to their ability to metabolize the herbicide. In the case of the chloro-triazines the conversion to the 2-hydroxy analogue, a non-phytotoxic product, has been described in the literature already. Studies which have been devoted to the metabolic breakdown of methylmercaptotriazines revealed a conversion to the 2-hydroxy compound to a smaller extent and in a way different from that established with the chloro-triazines. The in vitro oxidation of prometryne (2-methylmercapto-4, 6-bisisopropylamino-striazine) yields the sulphoxy and sulphono analogues which easily hydrolyse to 2-hydroxypropazine. The occurrence of these compounds in peas injected with 14C-prometryne could be established. Some recent findings concerning the occurrence of further metabolites with an intact triazine ring suggest that dealkylation or deamination of the side chains in the 4- and 6-position have to be considered too. Methods used in studying the metabolism of triazines and for the determination of 14CO2 released from treated plants are discussed. (author)

  7. Oxygen enhancement ratio (OER) and therapeutic gain factor (GF) for californium-252 at low dose rate

    International Nuclear Information System (INIS)

    The potential benefit of the introduction of californium-252 in interstitial and intracavitary therapy is related to the greater efficiency of its neutron emission against anoxic cancer cells. In that respect, the oxygen enhancement ratio (OER) of the 252Cf emission has been determined for a continuous low dose rate irradiation. The biological system is growth inhibition in Vicia faba bean roots. A new Vicia faba ''BelB'' strain has been used, which better tolerates long periods (up to about 10 hours) of anoxia. In a first series of experiments, for a 252Cf (Dsub(n+γ)) dose rate of 0.11 Gy.h-1, an OER of 1.4+-0.1 was observed (the γ contribution Dγ to the total absorbed dose Dsub(n+γ) was 0.35 at the position of the root tips). In a second series of experiments, in somewhat different geometrical conditions with a 252Cf (Dsub(n+γ)) dose rate of 0.13 Gy.h-1, an OER of 1.5+-0.1 was observed (Dγ/Dsub(n+γ)=0.42). The OER values observed for similar irradiation times, with iridium-192 γ-rays, were 2.3+-0.2 and 2.6+-0.1 respectively, which leads to therapeutic gain factors (GF) of 1.6 and 1.7 respectively. These GF values are slightly lower than those previously obtained (GF=1.8) on the same system, with d(50)-Be p(75)-Be and 15 MeV neutron beams

  8. Green Synthesis of Silver Nanorods and Optimization of Its Therapeutic Cum Toxic Dose.

    Science.gov (United States)

    Suganya, T R; Devasena, T

    2015-12-01

    Germinated Fenugreek seeds are relatively rich in flavonoids and polyphenols than dry seeds. Therefore, germinated fenugreek seeds possess better pharmacological activities. We have used an aqueous extract of germinated fenugreek seeds to reduce silver nitrate into nanoscale silver rods. The silver nanorods showed Surface Plasmon peak at 450 nm as revealed from UV visible spectrum. Field Emission Scanning Electron Microscopy images revealed the monodispersity and rod morphology. X ray diffraction spectrum revealed the FCC crystal structure of nanorods. Fourier transform infrared spectroscopy peaks revealed the interaction between the phytochemicals of germinated fenugreek seeds and the silver nanorods. Characterization studies reveal the validation of the proposed green synthesis protocol to produce monodispersed silver nanorods with phytochemical capping. The phytosynthesized silver nanorods exhibited anticancer activity in skin cancer cell line, which may be due to its nanoscale dimension and the surface functionalization. For the first time, we have optimized the therapeutic cum toxic dose of phytostabilized silver nanorods using skin cancer cell model. PMID:26682379

  9. Synthesis of {sup 14}C-labelled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), nitrocellulose (NC) and glycidyl azide polymer (GAP) for use in assessing the biodegradation potential of these energetic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ampleman, G.; Thiboutot, S.; Lavigne, J.; Marois, A. [Defence Research Establishment Valcartier, Courcelette, PQ (Canada); Hawari, J.; Jones, A.M.; Rho, D. [National Research Council of Canada, Ottawa, ON (Canada)

    1995-06-01

    Within the framework of an R and D project on bioremediation of soils contaminated with energetic compounds, the biodegradation of energetic products such as hexogen (RDX), trinitrotoluene (TNT), nitrocellulose (NC) and glycidyl azide polymer (GAP) is under study. Microcosm assays must be performed with radioactive carbon-14 labelled products in order to follow the biodegradation process. {sup 14}C-RDX was prepared by nitration of hexamethylenetetramine (HMTA) according to the Hale process. {sup 14}C-ring and methyl labelled TNTs synthesized according to the Dorey and Carper procedure. {sup 14}C-cellulose was synthesized from {sup 14}C-glucose by Acetobacter xylinum. Nitration of the {sup 14}C-cellulose yielded {sup 14}C-nitrocellulose. {sup 14}C-glycidyl azide polymer was obtained by polymerization and azidation of {sup 14}C-epichlorohydrin (ECH) which was synthesized from {sup 14}C-glycerol. Hydrochlorination of {sup 14}C-glycerol and epoxidation of the resulting {sup 14}C-1,3-dichloro 2-propanol yielded {sup 14}C-ECH. The syntheses of these {sup 14}C-labelled explosives are described in this paper. (Author).

  10. Optimization of the therapeutic dose of 131I for thyroid differentiated carcinoma

    International Nuclear Information System (INIS)

    organs, such as the narrow and gonads, of up to 78.4%.Possible benefits to the institution also include the use of less radioactive material and a reduction in radiation exposures to the staff during the manipulation and administration of the 131 I. To facilitate the calculations of the optimum therapeutic activity of 131 I for individual patients, a simple and fast dose planning program was created (PlanDose). The program has been set up to evaluate thryroid remant ablation, but it can also be used for the calculation of the activity to be administered for treatment of hyperthyroidism. This protocol of calculated optimal patient-specific 131 I. activities allows a better determination of the necessary ablative dose for patients with differentiated carcinoma of the thyroid, and is an example of optimizing the practice of radiation protection. (author)

  11. Reconstruction of biologically equivalent dose distribution on CT-image from measured physical dose distribution of therapeutic beam in water phantom

    International Nuclear Information System (INIS)

    From the standpoint of quality assurance in radiotherapy, it is very important to compare the dose distributions realized by an irradiation system with the distribution planned by a treatment planning system. To compare the two dose distributions, it is necessary to convert the dose distributions on CT images to distributions in a water phantom or convert the measured dose distributions to distributions on CT images. Especially in heavy-ion radiotherapy, it is reasonable to show the biologically equivalent dose distribution on the CT images. We developed tools for the visualization and comparison of these distributions in order to check the therapeutic beam for each patient at the National Institute of Radiological Sciences (NIRS). To estimate the distribution in a patient, the dose is derived from the measurement by mapping it on a CT-image. Fitting the depth-dose curve to the calculated SOBP curve also gives biologically equivalent dose distributions in the case of a carbon beam. Once calculated, dose distribution information can be easily handled to make a comparison with the planned distribution and display it on a grey-scale CT-image. Quantitative comparisons of dose distributions can be made with anatomical information, which also gives a verification of the irradiation system in a very straightforward way. (author)

  12. Dose evaluation of therapeutic radiolabeled bleomycin complexes based on biodistribution data in wild-type rats:Effect of radionuclides in absorbed dose of different organs

    Institute of Scientific and Technical Information of China (English)

    Hassan Yousefnia; Samaneh Zolghadri; Amir Reza Jalilian; Mohammad Ghannadi-Maragheh

    2015-01-01

    Bleomycins (BLMs), as tumor-seeking antibiotics, have been used for over 20 years in treatment of several types of cancers. Several radioisotopes are used in radiolabeling of BLMs for therapeutic and diagnostic purpos-es. An important points in developing new radiopharmaceuticals, especially therapeutic agents, is the absorbed dose delivered in critical organs. In this work, absorbed dose to organs after injection of 153Sm-, 177Lu-and 166Ho-labeled BLM was investigated by radiation dose assessment resource (RADAR) method based on biodis-tribution data in wild-type rats. The absorbed dose effect of the radionuclides was evaluated. The maximum absorbed dose for the complexes was observed in the kidneys, liver and lungs. For all the radiolabeled BLMs, bone and red marrow received considerable absorbed dose. Due to the high energy beta particles emitted by 166Ho, higher absorbed dose is observed for 166Ho-BLM in the most organs. The reported data can be useful for the determination of the maximum permissible injected activity of the radiolabeled BLMs in the treatment planning programs.

  13. Thyroid Remnant Estimation by Diagnostic Dose I131 Scintigraphy or TcO4-99m Scintigraphy after Thyroidectomy: A Comparison with Therapeutic Dose I131 Imaging

    Directory of Open Access Journals (Sweden)

    Guanghui Liu

    2016-01-01

    Full Text Available In this clinical study, we have compared routine diagnostic dose 131I scan and TcO4-99m thyroid scintigraphy with therapeutic dose 131I imaging for accurate thyroid remnant estimation after total thyroidectomy. We conducted a retrospective review of the patients undergoing total thyroidectomy for differentiated thyroid carcinoma (DTC and subsequently receiving radioactive iodine (RAI treatment to ablate remnant thyroid tissue. All patients had therapeutic dose RAI whole body scan, which was compared with that of diagnostic dose RAI, TcO4-99m thyroid scan, and ultrasound examination. We concluded that therapeutic dose RAI scan reveals some extent thyroid remnant in all DTC patients following total thyroidectomy. Diagnostic RAI scan is much superior to ultrasound and TcO4-99m thyroid scan for the postoperative estimation of thyroid remnant. Ultrasound and TcO4-99m thyroid scan provide little information for thyroid remnant estimation and, therefore, would not replace diagnostic RAI scan.

  14. Diagnostic Performance of Triagetrade mark for Benzodiazepines: Urine Analysis of the Dose of Therapeutic Cases.

    Science.gov (United States)

    Kurisaki, Emiko; Hayashida, Makiko; Nihira, Makoto; Ohno, Youkichi; Mashiko, Hirobumi; Okano, Takaaki; Niwa, Shin-Ichi; Hiraiwa, Kouichi

    2005-01-01

    We evaluated the diagnostic performance of Triage for benzodiazepines in 74 urine specimens from outpatients given therapeutic doses of benzodiazepines and compared the results of EMIT assays. Results obtained in all urine samples were confirmed using liquid chromatography-mass spectrometry (LC-MS). Overall agreement between results of Triage and EMIT assays was 73%. All of the Triage-positive samples were also positive by EMIT assays. Results of Triage and EMIT assays were different for 20 samples obtained from patients given thienodiazepines (etizolam, brotizolam, and clotiazepam) and nitrobenzodiazepines (nitrazepam, flunitrazepam, and clonazepam). LC-MS confirmed parent drugs in urine specimens, consistent with the prescriptions of drugs. The low agreement between Triage and EMIT results in this study might be due to low sensitivity of Triage for thienodiazepines. Thienodiazines are frequently prescribed benzodiazepines, and Triage panel is the most frequently used screening kit in Japan. It should be noted that negative results obtained by a Triage test might not mean the absence of thienodiazepines. PMID:16297284

  15. Diagnostic performance of Triage for benzodiazepines: urine analysis of the dose of therapeutic cases.

    Science.gov (United States)

    Kurisaki, Emiko; Hayashida, Makiko; Nihira, Makoto; Ohno, Youkichi; Mashiko, Hirobumi; Okano, Takaaki; Niwa, Shin-ichi; Hiraiwa, Kouichi

    2005-09-01

    We evaluated the diagnostic performance of Triage for benzodiazepines in 74 urine specimens from outpatients given therapeutic doses of benzodiazepines and compared the results of EMIT assays. Results obtained in all urine samples were confirmed using liquid chromatography-mass spectrometry (LC-MS). Overall agreement between results of Triage and EMIT assays was 73%. All of the Triage-positive samples were also positive by EMIT assays. Results of Triage and EMIT assays were different for 20 samples obtained from patients given thienodiazepines (etizolam, brotizolam, and clotiazepam) and nitrobenzodiazepines (nitrazepam, flunitrazepam, and clonazepam). LC-MS confirmed parent drugs in urine specimens, consistent with the prescriptions of drugs. The low agreement between Triage and EMIT results in this study might be due to low sensitivity of Triage for thienodiazepines. Thienodiazines are frequently prescribed benzodiazepines, and Triage panel is the most frequently used screening kit in Japan. It should be noted that negative results obtained by a Triage test might not mean the absence of thienodiazepines. PMID:16168176

  16. Effects of therapeutic and supratherapeutic doses of oral tedizolid phosphate on cardiac repolarisation in healthy volunteers: a randomised controlled study.

    Science.gov (United States)

    Flanagan, Shawn; Litwin, Jeffrey; Fang, Edward; Prokocimer, Philippe

    2016-07-01

    Drug-induced prolongation of the QT interval on the electrocardiogram (ECG) infrequently results in Torsades de pointes, a potentially fatal arrhythmia. Therefore, thorough QT analysis of new drugs is a regulatory requirement. The objective of this phase 1 study was to assess the effects of oral tedizolid phosphate on the QT interval corrected with Fridericia's formula (QTcF) in healthy adult subjects. A single therapeutic dose (200 mg) and a supratherapeutic dose (1200 mg) of tedizolid phosphate were administered to characterise QTc changes following typical systemic exposure and with markedly higher exposures, respectively. This was a four-way crossover study with 48 subjects randomly assigned to receive therapeutic and supratherapeutic doses of tedizolid phosphate, moxifloxacin (positive control for QT interval prolongation) and placebo (negative control). A continuous 12-lead ECG was recorded from 1 h before drug administration to 23 h after administration. Adverse events, which were generally mild, occurred most frequently with moxifloxacin or with a supratherapeutic dose of tedizolid phosphate; however, all treatments were well tolerated. This study demonstrated that therapeutic or supratherapeutic doses of the antibacterial tedizolid had no clinically significant effect on QT interval in healthy adults [ClinicalTrials.gov registration no.: NCT01461460]. PMID:27342387

  17. Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin

    Energy Technology Data Exchange (ETDEWEB)

    Keizer, B. de; Rijk, P.P. van; Klerk, J.M.H. de [Dept. of Nuclear Medicine, University Medical Center Utrecht (Netherlands); Koppeschaar, H.P.F.; Zelissen, P.M.J.; Lips, C.J.M. [Dept. of Endocrinology, University Medical Center Utrecht (Netherlands); Dijk, A. van [Dept. of Hospital Pharmacy, University Medical Center Utrecht (Netherlands)

    2001-02-01

    Serum thyroglobulin (Tg) is usually the best marker of residual or metastatic disease after treatment of differentiated thyroid cancer. We evaluated the effect of so-called blind therapeutic doses of iodine-131 in patients with detectable Tg during suppressive levothyroxine treatment (Tg-on), and in patients with a negative diagnostic scintigram but detectable Tg during the hypothyroid phase (Tg-off). Twenty-two patients with differentiated thyroid carcinoma underwent total thyroidectomy and radioiodine ablation. During the follow-up, six patients with detectable Tg-on and 16 patients with detectable Tg-off were identified. All patients were treated with a blind therapeutic dose of 7,400 MBq iodine-131. Diagnostic scintigrams were compared with post-treatment scintigrams. Tg-off was measured in 16 cases, 1 year after the administration of the blind therapeutic dose, at the time of the follow-up diagnostic scintigram. Six patients were followed up by Tg-on only. Post-therapy scintigrams revealed previously undiagnosed local recurrence or distant metastases in 13/22 cases (59%); the remaining nine post-therapy scintigrams were negative. At the time of the blind therapeutic doses, Tg-off values ranged from 8 to 608 {mu}g/l. After 1 year of follow-up, Tg-off decreased in 14/16 (88%) patients. In all patients who were followed by Tg-on only (n=6), a decrease in Tg values was measured. It is concluded that blind therapeutic doses resulted in a decrease in Tg levels in the majority of patients with suspected recurrence or metastases. The post-treatment scintigrams revealed pathological uptake in 59% of patients. (orig.)

  18. Absorbed dose to active red bone marrow from diagnostic and therapeutic uses of radiation

    International Nuclear Information System (INIS)

    The bone-marrow dose arising from radiological procedures as carried out in Australia have been determined as part of a survey of population doses. This paper describes the method of calculation of the radiation doses to the active bone marrow from diagnostic radiography, fluoroscopy and radiotherapy. The results of the calculations are compared with the results of other models of bone-marrow dose for a number of diagnostic X-ray procedures

  19. Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, M K; Eriksen, P B;

    1983-01-01

    Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

  20. Displaying 3D radiation dose on endoscopic video for therapeutic assessment and surgical guidance

    Science.gov (United States)

    Qiu, Jimmy; Hope, Andrew J.; Cho, B. C. John; Sharpe, Michael B.; Dickie, Colleen I.; DaCosta, Ralph S.; Jaffray, David A.; Weersink, Robert A.

    2012-10-01

    We have developed a method to register and display 3D parametric data, in particular radiation dose, on two-dimensional endoscopic images. This registration of radiation dose to endoscopic or optical imaging may be valuable in assessment of normal tissue response to radiation, and visualization of radiated tissues in patients receiving post-radiation surgery. Electromagnetic sensors embedded in a flexible endoscope were used to track the position and orientation of the endoscope allowing registration of 2D endoscopic images to CT volumetric images and radiation doses planned with respect to these images. A surface was rendered from the CT image based on the air/tissue threshold, creating a virtual endoscopic view analogous to the real endoscopic view. Radiation dose at the surface or at known depth below the surface was assigned to each segment of the virtual surface. Dose could be displayed as either a colorwash on this surface or surface isodose lines. By assigning transparency levels to each surface segment based on dose or isoline location, the virtual dose display was overlaid onto the real endoscope image. Spatial accuracy of the dose display was tested using a cylindrical phantom with a treatment plan created for the phantom that matched dose levels with grid lines on the phantom surface. The accuracy of the dose display in these phantoms was 0.8-0.99 mm. To demonstrate clinical feasibility of this approach, the dose display was also tested on clinical data of a patient with laryngeal cancer treated with radiation therapy, with estimated display accuracy of ˜2-3 mm. The utility of the dose display for registration of radiation dose information to the surgical field was further demonstrated in a mock sarcoma case using a leg phantom. With direct overlay of radiation dose on endoscopic imaging, tissue toxicities and tumor response in endoluminal organs can be directly correlated with the actual tissue dose, offering a more nuanced assessment of normal tissue

  1. Computerized clinical decision support systems for therapeutic drug monitoring and dosing: A decision-maker-researcher partnership systematic review

    Directory of Open Access Journals (Sweden)

    Weise-Kelly Lorraine

    2011-08-01

    Full Text Available Abstract Background Some drugs have a narrow therapeutic range and require monitoring and dose adjustments to optimize their efficacy and safety. Computerized clinical decision support systems (CCDSSs may improve the net benefit of these drugs. The objective of this review was to determine if CCDSSs improve processes of care or patient outcomes for therapeutic drug monitoring and dosing. Methods We conducted a decision-maker-researcher partnership systematic review. Studies from our previous review were included, and new studies were sought until January 2010 in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Inspec databases. Randomized controlled trials assessing the effect of a CCDSS on process of care or patient outcomes were selected by pairs of independent reviewers. A study was considered to have a positive effect (i.e., CCDSS showed improvement if at least 50% of the relevant study outcomes were statistically significantly positive. Results Thirty-three randomized controlled trials were identified, assessing the effect of a CCDSS on management of vitamin K antagonists (14, insulin (6, theophylline/aminophylline (4, aminoglycosides (3, digoxin (2, lidocaine (1, or as part of a multifaceted approach (3. Cluster randomization was rarely used (18% and CCDSSs were usually stand-alone systems (76% primarily used by physicians (85%. Overall, 18 of 30 studies (60% showed an improvement in the process of care and 4 of 19 (21% an improvement in patient outcomes. All evaluable studies assessing insulin dosing for glycaemic control showed an improvement. In meta-analysis, CCDSSs for vitamin K antagonist dosing significantly improved time in therapeutic range. Conclusions CCDSSs have potential for improving process of care for therapeutic drug monitoring and dosing, specifically insulin and vitamin K antagonist dosing. However, studies were small and generally of modest quality, and effects on patient outcomes were uncertain, with no convincing

  2. Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Reid F., E-mail: Reid.Thompson@uphs.upenn.edu [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Schneider, Ralf A., E-mail: ralf.schneider@psi.ch [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Albertini, Francesca; Lomax, Antony J.; Ares, Carmen; Goitein, Gudrun [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Hug, Eugen B. [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); ProCure Therapy Centers, New York, New York (United States)

    2013-05-01

    Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the

  3. Achievement of Therapeutic Goals with Low-Dose Imiglucerase in Gaucher Disease: A Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Irina Tukan

    2013-01-01

    Full Text Available Gaucher disease, a lysosomal storage disorder, is a multisystem disorder with variable and unpredictable onset and severity. Disease-specific enzyme replacement therapy (ERT has been shown to reverse or ameliorate disease-specific hepatosplenomegaly and anemia and thrombocytopenia. ERT also impacts bone manifestations, including bone crises, bone pain, and appearance of new osteonecrosis, and improves bone mineral density to varying degrees. The objective of this study was to assess achievement of predefined therapeutic goals based on international registry outcomes for Israeli patients with Gaucher disease receiving imiglucerase for four consecutive years on a low-dose regimen followed in a single center. All data were taken from patient files. The therapeutic goals were taken from standards published in the literature for disease-specific clinical parameters. Among 164 patients at baseline, values for spleen and liver volumes, hemoglobin and platelet counts, and Z-scores for lumbar spine and femoral were significantly different from the goal. After four years ERT, there was a significant improvement ( in each of the therapeutic goal parameters from baseline. 15.2% of these patients achieved all hematology-visceral goals. In children, there was achievement of linear growth and puberty. This survey highlights the good overall response in symptomatic patients receiving low-dose ERT with imiglucerase in Israel.

  4. Long-Term Impact of Immunosuppressants at Therapeutic Doses on Male Reproductive System in Unilateral Nephrectomized Rats: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Yehui Chen

    2013-01-01

    Full Text Available Cyclosporine, tacrolimus, and sirolimus are commonly used in renal transplant recipients to prevent rejection. However, information for comparative effects of these agents on the male productive system is extremely limited and controversial. In a physiologically and clinically relevant rat model of unilateral nephrectomy, we demonstrated that long-term oral administration of both cyclosporine and sirolimus at doses equivalent to the therapeutic levels used for postrenal transplant patients significantly affects testicular development and the hypothalamic-pituitary-gonadal axis accompanied by profound histological changes of testicular structures on both light and electron microscopic examinations. Spermatogenesis was also severely impaired as indicated by low total sperm counts along with reduction of sperm motility and increase in sperm abnormality after treatment with these agents, which may lead to male infertility. On the other hand, treatment with therapeutic dose of tacrolimus only induced mild reduction of sperm count without histological evidence of testicular injury. The current study clearly demonstrates that commonly used immunosuppressants have various impacts on male reproductive system even at therapeutic levels. Our data provide useful information for the assessment of male infertility in renal transplant recipients who wish to father children. Clinical trials to address these issues should be urged.

  5. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  6. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases

    Directory of Open Access Journals (Sweden)

    Go Taniguchi

    2015-01-01

    All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each, impaired consciousness appeared. Electroencephalography (EEG showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

  7. Dose enhancement in gold nanoparticle-aided radiotherapy for the therapeutic photon beams using Monte Carlo technique

    Directory of Open Access Journals (Sweden)

    Nitin Ramesh Kakade

    2015-01-01

    Full Text Available Background: Gold nanoparticle (GNP-aided radiation therapy (RT is useful to make the tumor more sensitive to radiation damage because of the enhancement in the dose inside the tumor region. Polymer gel dosimeter (PGD can be a good choice for the physical measurement of dose enhancement produced by GNP inside the gel. Materials and Methods: The present study uses EGSnrc Monte Carlo code to estimate dose enhancement factor (DEF due to the introduction of GNPs inside the PGD at different concentrations (7 and 18 mg Au/g of gel when irradiated by therapeutic X-rays of energy 100 kVp, 150 kVp, 6 MV, and 15 MV. The simulation was also carried out to quantify the dose enhancement in PAGAT gel and tumor for 100 kVp X-rays. Results: For 100 kVp X-rays, average DEF of 1.86 and 2.91 is observed in the PAGAT gel dosimeter with 7 and 18 mg Au/g of gel, respectively. Average DEF of 1.69 and 2.61 is recorded for 150 kVp X-rays with 7 and 18 mg Au/g of gel, respectively. No clinically meaningful DEF was observed for 6 and 15 MV photon beams. Furthermore, the dose enhancement within the PAGAT gel dosimeter and tumor closely matches with each other. Conclusion: The polymer gel dosimetry can be a suitable method of dose estimation and verification for clinical implementation of GNP-aided RT. GNP-aided RT has the potential of delivering high localized tumoricidal dose with significant sparing of normal structures when the treatment is delivered with low energy X-rays.

  8. Therapeutic dose simulation of a 6 MV Varian Linac photon beam using GEANT4

    Science.gov (United States)

    Salama, E.; Ali, A. S.; Khaled, N. E.; Radi, A.

    2015-10-01

    A developed program in C++ language using GEANT4 libraries was used to simulate the gantry of a 6 MV high energy photon linear accelerator (Linac). The head of a clinical linear accelerator based on the manufacturer's detailed information is simulated. More than 2× 109 primary electrons are used to create the phase space file. Evaluation of the percentage depth dose (PDD) and flatness symmetry (lateral dose profiles) in water phantom were performed. Comparisons between experimental and simulated data were carried out for three field sizes; 5 × 5, 10 × 10 and 15 × 15 cm2. A relatively good agreement appeared between computed and measured PDD. Electron contamination and spatial distribution for both photons and electrons in the simulated beam are evaluated. Moreover, the obtained lateral dose profiles at 15, 50, and 100 mm depth are compatible with the measured values. The obtained results concluded that, GEANT4 code is a promising applicable Monte Carlo program in radiotherapy applications.

  9. On the use of pulsed reduced dose rate for improvement of the therapeutic ratio

    Science.gov (United States)

    Rasmussen, Karl H., V.

    This work demonstrates three related aspects of the efficacy, delivery, and verification of pulsed reduced dose rate radiotherapy (PRDR). PRDR is a method of irradiation designed to minimize radiation-related toxicities in patients undergoing reirradiation for loco-regional reoccurrence of glioblastoma. PRDR uses 0.2GyX10fx daily doses delivered over a 30-minute time span. Under PRDR treatments, a subset of patients have had an unexpectedly positive response to treatment. It was a primary goal of this project to determine if low-dose hyper-radiosensitivity was a contributor to the increased radio-response from these patients. This was done through the use of human T98G glioma and HT29 colorectal cells, and V79.379-A Chinese hamster fibroblasts with drug inhibition of the p53 and PI3K pathways. Radiation was delivered with a medical linear accelerator in either 2Gy acute doses or through PRDR. Methods used to analyze the effect of these techniques included clonogenic assay, flow cytometry, and western blots. Comparison of survival ratios demonstrated no decrease in efficacy for either the standard T98G or HT29 cell lines when using PRDR as compared to an acute dose. T98G with PI3K inhibition and V79.397-A cells demonstrated a decreased efficacy of treatment using PRDR relative to an acute dose. These results suggest an equivalency in tumor treatment with a possible improvement in normal tissue toxicities for the PRDR method. An additional method of delivering PRDR through the use of Tomotherapy was proposed and demonstrated to be accurate. Tomotherapy planning forces the short leaf open times for individual MLC projections from low dose fractionation closed, resulting in an undeliverable plan due to the loss of a large number of usable projections. Application of a virtual grid with directional blocking allows for the output from useable segments to be above this threshold, resulting in a deliverable treatment plan. Finally, analysis was performed on a proposed QA

  10. Methodology to administer therapeutic dose of I-131; Metodologia para administrar dosis terapeutica de I-131

    Energy Technology Data Exchange (ETDEWEB)

    Basteris M, J.; Gomez D, R. [Universidad Autonoma de Yucatan, Facultad de Medicina, Merida, Yucatan (Mexico)

    2007-07-01

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment of the thyroid cancer with Iodine-131, as well as the use of citric fruits to stimulate the salivation, the post-dose administration of liquids to accelerate the gastric emptying avoiding the secondary effects as the vomit is included. (Author)

  11. Therapeutic drug monitoring to individualize the dosing of pazopanib: a pharmacokinetic feasibility study

    NARCIS (Netherlands)

    Wit, D. de; Erp, N. van; Hartigh, J. den; Wolterbeek, R..; Hollander-van Deursen, M. den; Labots, M.; Guchelaar, H.J.; Verheul, H.M.; Gelderblom, H.

    2015-01-01

    BACKGROUND: Patients treated with the standard dose of pazopanib show a large interpatient variability in drug exposure defined as the area under the plasma concentration-time curve (AUC0-24h). The primary objective of this study was to evaluate the feasibility of pharmacokinetics (PK)-guided indivi

  12. Is dosing of therapeutic immunoglobulins optimal? – A review of a 3-decade long debate in Europe.

    Directory of Open Access Journals (Sweden)

    Jacqueline eKerr

    2014-12-01

    Full Text Available The consumption of immunoglobulins (Ig is increasing due to better recognition of antibody deficiencies, an aging population and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals and infusion rates are paving the way towards more individualized therapy regimens.In primary antibody deficiencies adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic ‘per kg’ dosing.Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications, certain autoimmune disorders, immunosuppressive agents or biologics. This antibody failure, as shown by test immunisation, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings (e.g. ITP selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review the developments in dosing of therapeutic immunoglobulins have been

  13. Pregnancy after high therapeutic doses of iodine-131 in differentiated thyroid cancer: potential risks and recommendations

    International Nuclear Information System (INIS)

    Seventy female patients who had been treated with high doses of iodine-131 for differented thyroid cancer (DTC) and who had a subsequent pregnancy were evaluated. The global 131I dose ranged from 1.85 to 16.55 GBq (mean±SD=4.39±25.20 GBq). Age at first therapy ranged from 15 to 36 years (mean±SD=24.3±5.0 years) and the interval from 131I therapy to pregnancy varied from 2 to 10 years (mean±SD=5.3±2.8 years). The estimated radiation dose to the gonads ranged from 10 to 63 cGy (mean±SD=24.0±13.5 cGy). All patients were treated with L-thyroxine at doses capable of suppressing thyroid-stimulating hormone. Seventy-three children were followed-up and seven pregnancies are still in progress. One child was affected by Fallot's trilogy and three had a low birth weight though with subsequent regular growth; the others were healthy with subsequent regular growth. No newborn with clinical or biochemical thyroid dysfunctions was found. Two spontaneous abortions during the second month of pregnancy were recorded. One of two patients in question subsequently had two healthy children. On the basis of these data, previous administration of high 131I doses does not appear to be a valid reason for dissuading young female DTC patients from considering pregnancy. However, patients should be advised to avoid pregnancy after 131I administration for a period sufficient to ensure complete elimination of the radionuclide and to permit confirmation of complete disease remission, i.e. at least 1 year in our opinion. (orig.)

  14. Therapeutic efficacy of small doses of colchicine combined with glucocorticoid for acute gouty arthritis

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2015-10-01

    Full Text Available Objective To observe the clinical effect of small dose of colchicine combined with glucocorticoid for acute gouty arthritis. Methods Ninety-two patients with acute gouty arthritis were equally and randomly divided into small doses of colchicine combined with dexamethasone treatment group (treatment group and conventional large dose colchicine treatment group (control group between January 2009 and December 2013. The articular lesion scoring and clinical efficacy evaluation were performed at 3, 6, 12, 24, 48, and 72h after treatment. Erythrocyte sedimentation rate (ESR, white blood cells, hepatorenal function and glomerular filtration rate (GFR were determined before and 72h after treatment respectively. The gastrointestinal adverse events and recurrence rate were observed within one month after treatment. Results The articular lesion scores were significantly decreased at 6, 12, 48, and 72h after treatment in treatment group compared with control group (P0.05. Serum uric acid, glutamic-pyruvic transaminase in serum (SGPT, and GFR did not show any change before and 72h after the treatment, and there was also no significant difference between groups (P>0.05. The incidence of gastrointestinal adverse events were obviously higher in control group (76.1% compared with that of the treatment group (P<0.05, and the differences was statistically significant. There was no statistical difference in recurrence rate between the control group and treatment group after a follow-up of one month. Conclusions Compared with conventional large dose colchicine, small dose of colchicine combined with dexamethasone can more rapidly and effectively control acute gouty arthritis, with good tolerability and safety, thus being worthy of popularization clinically. DOI: 10.11855/j.issn.0577-7402.2015.08.10

  15. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs.

    Science.gov (United States)

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-03-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.

  16. High dose intravitreal ganciclovir injection provides a prolonged therapeutic intraocular concentration.

    OpenAIRE

    Morlet, N; Young, S; Naidoo, D; Graham, G.; Coroneo, M T

    1996-01-01

    BACKGROUND: Although intravitreal high dose ganciclovir has previously been found to provide excellent control of cytomegalovirus (CMV) retinitis, little was known about the vitreous concentrations of ganciclovir after a 2 mg intravitreal injection. METHODS: Eleven vitreous samples were taken from seven patients with CMV retinitis at 24 and 72 hours after a 2 mg intravitreal injection of ganciclovir and the concentration of ganciclovir was measured by high performance liquid chromatography. R...

  17. The effect of a metal hip prosthesis on the radiation dose in therapeutic photon beam irradiations

    International Nuclear Information System (INIS)

    Prostate and cervical cancer patients are often treated with external X-ray beams of bi-lateral incidence. Such treatment may incur some dose effect that cannot be predicted precisely in commercial treatment planning systems (TPS) for patients having undergone total hip replacement. This study performs a Monte Carlo (MC) simulation and an analytical calculation (convolution superposition algorithm which is implemented in ADAC TPS) of a 6 MV, 5x5 cm2 X-ray beam incident into water with the existence of hip prosthesis, e.g. Ti6Al4V and CoCrMo alloy. The results indicate that ADAC TPS cannot precisely account for the scatter and backscatter radiation that a metal hip prosthesis causes. For percent depth dose (PDD) curves, the maximum underdosage of ADAC TPS up to 5 mm above the interface between dense material and water is 5%, 20% and 27% for PDDBone, PDDTi and PDDCo, respectively. The dose re-buildup, which occurs behind the hip region, becomes more and more obvious for denser medium existed in water. Increasing inhomogeneity also enhances the underdosage of ADAC for greater depth (>10 cm), as the figures of nearly 2% in PDDBone, PDDTi and 4-5% in PDDCo reveal. Overestimating the attenuated power of high-density non-water material in ADAC TPS causes this underdosage. For dose profiles, no significant differences were found in ProfileBone at any depth. ProfileTi reveals that MC slightly exceeds ADAC at off-axis position 1.0-2.0 cm. ProfileCo reveals this more obviously. This finding means that scatter radiation from these denser materials is significant and cannot be predicted precisely in ADAC

  18. Calculation of energy spectra for the therapeutic electron beams from depth-dose curves

    International Nuclear Information System (INIS)

    In this note the algorithm for calculation of the electron energy spectrum from the depth-dose curve was tested by data on a 4 MeV linear accelerator with scanning beam. A Perspex phantom with cellulose triacetate dosimetric films was irradiated on a conveyor moving perpendicularly to the area of beam scanning, thus simulating irradiation by broad beam. Excellent agreement between measured and calculated spectra is claimed. (U.K.)

  19. Therapeutic Potential of Green Tea Extract and Low Doses of Irradiation on Diabetic Nephropathy of Rats

    Directory of Open Access Journals (Sweden)

    Hanafy N.A. and Hanaa F. Waer

    2009-09-01

    Full Text Available Introduction: Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. This study was designed to evaluate the effect of green tea (GT extract and low doses of 0.5 Gy -radiation (R on diabetic nephropathy (DN of rats. Materials and methods: Male Swiss albino rats were used in this study. DN was induced in rats using streptozotocin (45 mg/kg body weight. The rats were divided into five groups DN, DN+R, DN+GT, DN+GT+R and a sham treatment control group. Throughout the experimental period (3and 6 weeks animals body weight, glucose and insulin levels were evaluated. Kidney functions assay (serum urea and creatinin were recorded. Histopathological observations in kidney tissue, DNA and glycogen intensity were also detected. Results: Diabetic rats exhibited many symptoms including loss of body weight, increase in blood glucose level and decrease in serum insulin levels. Increase in serum urea and creatinin levels. Diabetic kidney showed a moderate renal damage, multifocal clarifications and vacuolations. Carbohydrates intensity showed a significant increase and DNA intensity showed many alterations. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group exposed to low doses of -radiation or supplemented by green tea either alone or combined in addition to amelioration in glucose, insulin urea and creatinin levels. Conclusion: The present study demonstrates the efficacy of low doses of - radiation and in reducing diabetes-induced functional and histological alterations in the kidneys. The longterm control of blood glucose levels using low doses of -radiation or green tea either alone or combined could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented.

  20. Therapeutic dose simulation of a 6 MV Varian Linac photon beam using GEANT4

    International Nuclear Information System (INIS)

    A developed program in C++ language using GEANT4 libraries was used to simulate the gantry of a 6 MV high energy photon linear accelerator (Linac). The head of a clinical linear accelerator based on the manufacturer's detailed information is simulated. More than 2× 109 primary electrons are used to create the phase space file. Evaluation of the percentage depth dose (PDD) and flatness symmetry (lateral dose profiles) in water phantom were performed. Comparisons between experimental and simulated data were carried out for three field sizes; 5 × 5, 10 × 10 and 15 × 15 cm2. A relatively good agreement appeared between computed and measured PDD. Electron contamination and spatial distribution for both photons and electrons in the simulated beam are evaluated. Moreover, the obtained lateral dose profiles at 15, 50, and 100 mm depth are compatible with the measured values. The obtained results concluded that, GEANT4 code is a promising applicable Monte Carlo program in radiotherapy applications

  1. POSSIBLE CARDIAC ADVERSE EFFECTS OF THERAPEUTIC DOSES OF MACROLIDE ANTIBIOTICS (AZITHROMYCIN AND CLARITHROMYCIN IN HEALTHY JUVENILE RATS: BIOCHEMICAL ASSESSMENT

    Directory of Open Access Journals (Sweden)

    Kassim Hassoon Ali

    2012-09-01

    Full Text Available The macrolides antibiotics inhibit bacterial protein synthesis by an effect on translocation. They include erythromycin, azithromycin, clarithromycin, and roxithromycin . Their antimicrobial spectrum is varied. The drugs are associated with QT interval prolongation and cardiac dysrhythmias. This study was designed to determine whether or not a therapeutic oral dose of either azithromycin or clarithromycin administered for 5 or 10 days, respectively have cardiac adverse effects in healthy juvenile rats by assessing serum enzymes (CK-MB, LDH, AST and ALT, as markers of cardiac function. Twenty-eight healthy juvenile rats of both sexes weighing approximately 30gm were utilized and were randomly subdivided into 4 groups, control group orally-administered distilled water (DW every 12hrs for 5 days via gavage tube, azithromycin suspension 12 mg/ kg every 12 hrs for 5 days via gavage tube, control group orally-administered DW every 12 hrs for 10 days via gavage tube and clarithromycin suspension 7.5 mg per kg for every 12 hrs for10 days via gavage tube. After scarification of animals by cervical dislocation, blood samples were taken by intra-cardiac puncture and utilized immediately to get serum in order to assess enzymes activities {heart creatin kinase isoform (CK-MB, lactate dehydrogenase (LDH, aspartate aminotransferase (AST and alanine aminotransferase (ALT}.The results of the present study demonstrated that were significant increase in serum activities of both CK-MB and LDH in group of animals treated with therapeutic oral dose of (12mg/kg azithromycin for 5 days compared to the corresponding serum enzyme activities of control animals. While, there were no significant increase in serum activities of both AST and ALT in group of animals treated with therapeutic oral dose of (12mg/kg azithromycin for 5 days compared to the corresponding serum enzyme activities of control group. Moreover, in groups of animals treated with therapeutic oral dose of (7

  2. Optimizing therapeutics in the management of patients with multiple sclerosis: a review of drug efficacy, dosing, and mechanisms of action

    Directory of Open Access Journals (Sweden)

    Damal K

    2013-11-01

    Full Text Available Kavitha Damal, Emily Stoker, John F FoleyRocky Mountain Multiple Sclerosis Research Group, Salt Lake City, UT, USAAbstract: Multiple sclerosis (MS is a debilitating neurological disorder that affects nearly 2 million adults, mostly in their prime of youth. An environmental trigger, such as a viral infection, is hypothesized to initiate the abnormal behavior of host immune cells: to attack and damage the myelin sheath surrounding the neurons of the central nervous system. While several other pathways and disease triggers are still being investigated, it is nonetheless clear that MS is a heterogeneous disease with multifactorial etiologies that works independently or synergistically to initiate the aberrant immune responses to myelin. Although there are still no definitive markers to diagnose the disease or to cure the disease per se, research on management of MS has improved many fold over the past decade. New disease-modifying therapeutics are poised to decrease immune inflammatory responses and consequently decelerate the progression of MS disease activity, reduce the exacerbations of MS symptoms, and stabilize the physical and mental status of individuals. In this review, we describe the mechanism of action, optimal dosing, drug administration, safety, and efficacy of the disease-modifying therapeutics that are currently approved for MS therapy. We also briefly touch upon the new drugs currently under investigation, and discuss the future of MS therapeutics.Keywords: multiple sclerosis, immunomodulation, interferons, glatiramer acetate, monoclonal antibodies, dimethyl fumarate

  3. Plasma quetiapine in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 2000–2011

    Science.gov (United States)

    Bowskill, Sally V.J.; Patel, Maxine X.; Flanagan, Robert J.

    2013-01-01

    Objective: Suggested predose plasma quetiapine target ranges for effective therapy in schizophrenia lie between 50 and 500 µg/l. We aimed to examine data from a quetiapine therapeutic drug monitoring (TDM) service to assess the plasma quetiapine concentrations attained at specified doses in clinical practice. Method: We studied TDM data from patients given immediate-release quetiapine in the period 2000–2011. Results: There were 946 samples from 487 patients (257 males, age at time of first sample, median [range] 34 [14–87] years, and 230 females, age at time of first sample, median [range] 38 [10–92] years). The plasma quetiapine concentration was <50 and <100 µg/l in 30% and 50% of samples, respectively (no quetiapine detected in 9% of samples). The relationship between dose and plasma quetiapine was poor. The mean (95% confidence interval [CI]) quetiapine dose was higher (t = 3.6, df = 446, p <0.01) in males versus females (641 [600–1240] and 548 [600–943] mg/day, respectively), although there was no difference in median dose (600 mg/day) or in the mean (95% CI) plasma quetiapine concentrations attained. Smoking habit had no discernible effect on plasma quetiapine concentration. Conclusions: There was a poor relationship between dose and plasma quetiapine concentration in this study, as found by others. This is probably because of the short plasma half-life of the drug, at least in part. Nevertheless, quetiapine TDM can help assess adherence and measurement of quetiapine metabolites, notably N-desalkylquetiapine, as well as quetiapine itself may enhance the value of quetiapine TDM in future. PMID:24167685

  4. Evaluating the Therapeutic Dose Distribution of Intensity-Modulated Radiation Therapy for Head and Neck with Cone-Beam Computed Tomography Image: A Methodological Study

    OpenAIRE

    Guang-shun Zhang; Shao-min Huang; Cui Chen; Sen-kui Xu; Dan-dan Zhang; Xiao-wu Deng

    2014-01-01

    An approximate correction method for the CT value-electron density curve of CBCT was established, through comparison and fitting with FBCT images, and applied to evaluate the therapeutic dose of IMRT. The precision of using CBCT for plan calculation was validated by comparing the dose distribution between CBCT- and FBCT-based IMRT plans. Also setup deviations were simulated to evaluate the ability of the CBCT-based calculation for detecting the dose errors caused by positioning deviation. The...

  5. MCNP Dose Calculations in a CT Phantom for Therapeutic External Photon Beam

    Institute of Scientific and Technical Information of China (English)

    Lamyae El Gonnouni; Tarek El Bardouni; Mariam Zoubair; Mohamed Idaornar; Abderrahmane Senhoo

    2011-01-01

    In this paper, we have addressed the problem of the radiation transport with the Monte Carlo N-particle(MCNP) code. This is a general-purpose Monte Carlo tool designed to transport neutron, photon and electron in three dimensional geometries. To examine the performance of MCNP5 code in the field of external radiotherapy, we performed the modeling of an Electron Density phantom (EDP) irradiated by photons from 60Co source. The model was used to calculate the Percent Depth Dose (PDD) at different depths in an EDP. One field size for PDD has been examined. A 60Co photons source placed at 80 cm source to surface distance (SSD). The results of calculations were compared to TPS data obtained at National Institute of Oncology of Rabat.

  6. Study on the therapeutic effect of small dose of estradiol and progesterone on post-menopausal osteoporosis

    International Nuclear Information System (INIS)

    Objective: To explore the therapeutic effect and possible adverse side-effects of small dose of estradiol and progesterone on postmenopausal osteoporosis. Methods: Applying a GBD-928 mono-photon BMD radiometer, 68 women (past-menopausal over 3 years, age 52-59, body weight index 2 0.5 mg with MPA (medroxyprogesterone acetate) 0.5 mg daily. The medication laster for a whole years and BMD value was measured again. All subjects underwent gynecological physical examination, vaginal sonography, vaginal smear study and breast examination with infra-red ray both before and after the test period. Results: After one year medication, mean value of BMD in Group A was 0.49 ± 0.05, three percentage points higher than before. In Group B, this was 0.52 ± 0.06, another three percentage points higher. Ten Women with mild lobular hyperplasia and nine women with small uterine myoma (3) were all allocated to the hormone treated group. The lesions showed either little change or slight regression after the test period. Conclusion: Osteoporotic women receiving additional small doses of female hormones responded much better than those receiving calcium only. The WHI report which advised against HRT should be more critically studied

  7. Optimization of the therapeutic dose of {sup 131}I for thyroid differentiated carcinoma; Otimizacao da dose terapeutica com {sup 131}I para carcinoma diferenciado da tiroide

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Fabiana Farias de

    2002-09-01

    reduction for many organs, such as the narrow and gonads, of up to 78.4%.Possible benefits to the institution also include the use of less radioactive material and a reduction in radiation exposures to the staff during the manipulation and administration of the {sup 131} I. To facilitate the calculations of the optimum therapeutic activity of {sup 131} I for individual patients, a simple and fast dose planning program was created (PlanDose). The program has been set up to evaluate thryroid remant ablation, but it can also be used for the calculation of the activity to be administered for treatment of hyperthyroidism. This protocol of calculated optimal patient-specific {sup 131} I. activities allows a better determination of the necessary ablative dose for patients with differentiated carcinoma of the thyroid, and is an example of optimizing the practice of radiation protection. (author)

  8. A simple and fast physics-based analytical method to calculate therapeutic and stray doses from external beam, megavoltage x-ray therapy

    OpenAIRE

    Wilson, Lydia J; Newhauser, Wayne D.

    2015-01-01

    State-of-the-art radiotherapy treatment planning systems provide reliable estimates of the therapeutic radiation but are known to underestimate or neglect the stray radiation exposures. Most commonly, stray radiation exposures are reconstructed using empirical formulas or lookup tables. The purpose of this study was to develop the basic physics of a model capable of calculating the total absorbed dose both inside and outside of the therapeutic radiation beam for external beam photon therapy. ...

  9. Sand as thermoluminescent dosimeter to therapeutic doses Arena como dosímetro termoluminiscente para dosis terapéuticas

    Directory of Open Access Journals (Sweden)

    Juana Salcedo

    2010-06-01

    Full Text Available This work describes the characteristic thermoluminiscent of sand coming from Coveñas beaches, for its use as therapeutic dose dosimeter. The selected samples, annealed at 400oC during 1 hour, were irradiated to different doses using an unit of 60Co Theratron 780C in air to ambient temperature. The reading was carried out in a Harshaw TLD 4500. The main dosimetric properties of the material (glow curve, response reproducibility, reutilization, linearity and thermal decay have been studied in detail. The glow curve of the sand samples presents a peaks TL at about 145◦C. The results show that the material has a linear response to the dose from 50 cGy until 1000 cGy. The studied sand samples can be used as thermoluminescent dosimeters for applications in different areas. The importance of this work is that the sand is a natural substance available in large quantities, low cost and can be used in clinical physics to evaluate the dose received by the patient during medical treatment.Este trabajo describe las características termoluminiscentes de arena proveniente de las playas de Coveñas para su uso como dosímetro en dosis terapéuticas. Las muestras seleccionadas, tratadas térmicamente a 400◦C por una hora, fueron irradiadas a diferentes dosis usando una unidad de 60Co Theratron 780C en aire a temperatura ambiente. La lectura se realizó en un Harshaw TLD 4500. Las principales propiedades dosimétricas del material (curva de brillo, reproducibilidad de la respuesta, reutilización, linealidad y decaimiento térmico han sido estudiadas en detalle. La curva de brillo de las muestras de arena presenta un pico TL alrededor de los 145◦C. Los resultados muestran que el material tiene una respuesta lineal con la dosis desde 50 cGy hasta 1000 cGy. Las muestras de arena estudiadas se pueden utilizar como dos´ımetros termoluminiscentes para aplicaciones en diferentes áreas. La importancia de este trabajo radica en que la arena es una sustancia

  10. Early treatment with addition of low dose prednisolone to methotrexate improves therapeutic outcome in severe psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Vikram K Mahajan

    2013-01-01

    Full Text Available Psoriatic arthritis (PsA is increasingly being recognized to cause progressive joint damage and disability. PsA unresponsive to non-steroidal anti-inflammatory drugs (NSAIDs, the conventional first-line choice of treatment, is usually managed with disease-modifying antirheumatic drugs (DMARDs especially methotrexate. An 18-year-old HIV-negative male had progressively severe PsA of 4-month duration that was nearly confining him to a wheel chair. He did not respond to multiple NSAIDs, alone or in combination with methotrexate (15 mg/week, given for 4 weeks. Addition of prednisolone (10 mg on alternate days controlled his symptoms within a week. The NSAIDs could be withdrawn after 4 weeks as the treatment progressed. The doses were tapered for methotrexate (5 mg/week and prednisolone (2.5 mg on alternate days every 8 weekly subsequently during 15 months of follow-up without recurrence/deformities or drug toxicity. For years, the use of corticosteroids in psoriasis has been criticized for their propensity to exacerbate the skin disease on withdrawal. However, monitored use of corticosteroids, even in low doses, combined with DMARDs may be a good therapeutic option in early stage of the PsA rather than ′steroid rescue′ later. This will help in early control of joint inflammation, prevent joint damage and maintain long-term good functional capacity and quality of life. This may be useful when the cost or availability of biologics precludes their use. However, we discourage the use of corticosteroids as monotherapy.

  11. The comparison of the proton dose distribution calculated with the treatment planning system and measured with alanine detectors in the eye phantom irradiated under therapeutic conditions

    International Nuclear Information System (INIS)

    The paper describes the applicability of commercially available alanine detectors produced by Synergy Health for verification of the dose distribution calculated by the treatment planning system (TPS) used in proton eye radiotherapy – Eclipse Ocular Proton Planning (EOPP) program, version 8.9.06, Varian Medical Systems. The TPS-planned dose distribution at selected points in the eye phantom is compared to the dose registered by alanine detectors at these points during a simulated therapeutic irradiation at the proton eye radiotherapy facility in the Henryk Niewodniczanski Institute of Nuclear Physics (IFJ PAN), Krakow, Poland. The phantom was irradiated to obtain, a typical for choroidal melanoma, fraction dose of 15 CGE (13,64 Gy) at the tumor location. The dose registered with alanine pellets located inside the simulated tumor volume demonstrates a good agreement with the TPS-planned dose. The typical for proton radiotherapy, steep dose fall-off outside the treated area is registered by the alanine pellets however, it is difficult to assess it quantitatively, because the dose related EPR signal is registered from the entire pellet volume. - Highlights: • We confirmed the utility of alanine for in-phantom measurements in proton beams. • We compared TPS-planned and measured doses in proton eye radiotherapy simulation. • We discovered the limitation of alanine in registration the high dose gradients

  12. The influence of position deviation on RAIU and the corresponding therapeutic dose calculations in patients with Graves hyperthyroidism

    International Nuclear Information System (INIS)

    .8% compared with CⅠ. Conclusions: Incorrect positioning in RAIU detection could result in various false RAIU, Teff and 131I dose calculations. Such deviations could possibly exert an impact on the patients' therapeutic outcomes,thus influencing the efficacy of the iodine therapy. Optimization of RAIU positioning is essential for clinical practice to guarantee radioiodine dose management. (authors)

  13. POSSIBLE ADVERSE EFFECTS OF ONCE-DAILY ORAL THERAPEUTIC DOSE OF EITHER GLUCOSAMINE SULFATE OR GLUCOSAMINE/CHONDROITIN SULFATE ON BLOOD CELLS COUNT IN RATS

    Directory of Open Access Journals (Sweden)

    Noushi Abeer Amer

    2013-10-01

    Full Text Available This study was designed to investigate the possible adverse effects that may be induced by once-daily therapeutic doses of either glucosamine sulfate or glucosamine/chondroitin sulfate administered orally to rats for 30 days on blood cells (RBCs, WBCs and platelets counts. Forty three white healthy adult Albino rats of both sexes were selected randomly for this study. They were divided into three groups (І, ІІ, ІІІ. Group І received 0.05 ml distilled water, group ІІ received once daily therapeutic dose of glucosamine sulphate and group ІІІ received once daily therapeutic dose of glucosamine sulphate/chondroitin sulphate orally. The treatment period was for 30 days. At day 31, the animals were subjected to light ether anaesthesia and blood was withdrawn from the eye by retro-orbital puncture for the estimation of blood cells (RBCs, WBCs and platelets count. Treatment with single daily therapeutic dose of either GS alone or GS/CS for 30 days on blood cells count in rats produced a non significant change in RBCs counts compared to control and to each other. There were no statistically significant differences in total WBCs count at day 31 in animals administered once daily therapeutic dose of either GS or GS/CS orally compared to control group. In contrast, there was a statistically significant elevation in total WBCs count in GS/CS- treated rats compared to that in the GS-treated rats. The results of this study also showed that there was statistically significant decrease in neutrophils percentage in both drug treatment groups compared to control group. A statistically significant reduction in the percentage of monocytes was observed in GS/CS group compared to the corresponding percentage in animals of control group; while, there were non-significant differences in the percentage of monocytes in GS treated rats compared to that in the control group. There were no significant differences in the percentage of monocytes at day 31 of GS

  14. Evaluating the therapeutic dose distribution of intensity-modulated radiation therapy for head and neck with cone-beam computed tomography image: a methodological study.

    Science.gov (United States)

    Zhang, Guang-shun; Huang, Shao-min; Chen, Cui; Xu, Sen-kui; Zhang, Dan-dan; Deng, Xiao-wu

    2014-01-01

    An approximate correction method for the CT value-electron density curve of CBCT was established, through comparison and fitting with FBCT images, and applied to evaluate the therapeutic dose of IMRT. The precision of using CBCT for plan calculation was validated by comparing the dose distribution between CBCT- and FBCT-based IMRT plans. Also setup deviations were simulated to evaluate the ability of the CBCT-based calculation for detecting the dose errors caused by positioning deviation. The gamma comparison between CBCT- and FBCT-based dose computations showed that the pass rates of (2%, 2 mm) criteria were better than 97.60 ± 0.83% and 97.74 ± 2.08% in the phantom and 10 NPC cases. When setup deviation was introduced into CBCT-based dose calculation, the gamma pass rate significantly decreased while the volumetric doses of the targets and some normal organs exhibited different changes compared to the original plan. Our results validated the above CT value-electron density correction which reduced the difference between CBCT- and FBCT-based IMRT plan calculation for NPC to less than 2%. Online CBCT-based dose calculation can be used to reflect and evaluate the dose distribution discrepancy caused by setup deviation and structure changes during the treatment, ensuring more effective quality control of IMRT treatment. PMID:25197637

  15. Evaluating the Therapeutic Dose Distribution of Intensity-Modulated Radiation Therapy for Head and Neck with Cone-Beam Computed Tomography Image: A Methodological Study

    Directory of Open Access Journals (Sweden)

    Guang-shun Zhang

    2014-01-01

    Full Text Available An approximate correction method for the CT value-electron density curve of CBCT was established, through comparison and fitting with FBCT images, and applied to evaluate the therapeutic dose of IMRT. The precision of using CBCT for plan calculation was validated by comparing the dose distribution between CBCT- and FBCT-based IMRT plans. Also setup deviations were simulated to evaluate the ability of the CBCT-based calculation for detecting the dose errors caused by positioning deviation. The gamma comparison between CBCT- and FBCT-based dose computations showed that the pass rates of (2%, 2 mm criteria were better than 97.60 ± 0.83% and 97.74 ± 2.08% in the phantom and 10 NPC cases. When setup deviation was introduced into CBCT-based dose calculation, the gamma pass rate significantly decreased while the volumetric doses of the targets and some normal organs exhibited different changes compared to the original plan. Our results validated the above CT value-electron density correction which reduced the difference between CBCT- and FBCT-based IMRT plan calculation for NPC to less than 2%. Online CBCT-based dose calculation can be used to reflect and evaluate the dose distribution discrepancy caused by setup deviation and structure changes during the treatment, ensuring more effective quality control of IMRT treatment.

  16. A simple and fast physics-based analytical method to calculate therapeutic and stray doses from external beam, megavoltage x-ray therapy.

    Science.gov (United States)

    Jagetic, Lydia J; Newhauser, Wayne D

    2015-06-21

    State-of-the-art radiotherapy treatment planning systems provide reliable estimates of the therapeutic radiation but are known to underestimate or neglect the stray radiation exposures. Most commonly, stray radiation exposures are reconstructed using empirical formulas or lookup tables. The purpose of this study was to develop the basic physics of a model capable of calculating the total absorbed dose both inside and outside of the therapeutic radiation beam for external beam photon therapy. The model was developed using measurements of total absorbed dose in a water-box phantom from a 6 MV medical linear accelerator to calculate dose profiles in both the in-plane and cross-plane direction for a variety of square field sizes and depths in water. The water-box phantom facilitated development of the basic physical aspects of the model. RMS discrepancies between measured and calculated total absorbed dose values in water were less than 9.3% for all fields studied. Computation times for 10 million dose points within a homogeneous phantom were approximately 4 min. These results suggest that the basic physics of the model are sufficiently simple, fast, and accurate to serve as a foundation for a variety of clinical and research applications, some of which may require that the model be extended or simplified based on the needs of the user. A potentially important advantage of a physics-based approach is that the model is more readily adaptable to a wide variety of treatment units and treatment techniques than with empirical models.

  17. Subacute therapeutic dosing of artemether-lumefantrine and artesunate-amodiaquine combination preserves plasma cholesterol, renal antioxidant status, and organ weights in rats.

    Science.gov (United States)

    Otuechere, Chiagoziem A; Edewor, Gloria; Kale, Oluwafemi Ezekiel; Ekor, Martins

    2012-01-01

    Recent instances of breakdowns of malaria control programs and the constant emergence of drug-resistant parasites to monotherapies have shored up the use of artemisinin-based combination therapy (ACT) as the malaria therapy of choice. We evaluated a subacute therapeutic dosing of artemether-lumefantrine and artesunate-amodiaquine on plasma cholesterol, renal antioxidants, and organ weights in rats. Sixteen albino rats were grouped into three. Group A (n = 5) served as the control. Groups B (n = 6) and C (n = 5) were administered, twice daily, oral therapeutic doses of artemether-lumefantrine (1.14/6.86 mg/kg/d) and artesunate-amodiaquine (2.86/8.58 mg/kg/d), respectively, for seven days. From our results, ACTs did not significantly (P > 0.05) alter catalase, superoxide dismutase, glutathione S-transferase, myeloperoxidase, and total glutathione levels when compared with the control. Plasma total cholesterol levels also decreased insignificantly (P > 0.05). Organ-system weights were not significantly (P > 0.05) different from control rats. Artesunate-amodiaquine, but not artemether-lumefantrine, significantly increased (P artesunate-amodiaquine and artemether-lumefantrine may preserve renal antioxidants and organ weights in vivo. However, caution is required above therapeutic indications or in chronic doses as this may predispose to renal oxidative stress.

  18. Preclinical Efficacy and Safety Profile of Allometrically Scaled Doses of Doxycycline Used to Turn "On" Therapeutic Transgene Expression from High-Capacity Adenoviral Vectors in a Glioma Model.

    Science.gov (United States)

    VanderVeen, Nathan; Raja, Nicholas; Yi, Elizabeth; Appelman, Henry; Ng, Philip; Palmer, Donna; Zamler, Daniel; Dzaman, Marta; Lowenstein, Pedro R; Castro, Maria G

    2016-06-01

    Glioblastoma multiforme (GBM) is the most commonly occurring primary brain cancer in adults, in whom its highly infiltrative cells prevent total surgical resection, often leading to tumor recurrence and patient death. Our group has discovered a gene therapy approach for GBM that utilizes high-capacity "gutless" adenoviral vectors encoding regulatable therapeutic transgenes. The herpes simplex type 1-thymidine kinase (TK) actively kills dividing tumor cells in the brain when in the presence of the prodrug, ganciclovir (GCV), whereas the FMS-like tyrosine kinase 3 ligand (Flt3L) is an immune-stimulatory molecule under tight regulation by a tetracycline-inducible "Tet-On" activation system that induces anti-GBM immunity. As a prelude to a phase I clinical trial, we evaluated the safety and efficacy of Food and Drug Administration (FDA)-approved doses of the tetracycline doxycycline (DOX) allometrically scaled for rats. DOX initiates the expression of Flt3L, which has been shown to recruit dendritic cells to the brain tumor microenvironment-an integral first step in the development of antitumor immunity. The data revealed a highly safe profile surrounding these human-equivalent doses of DOX under an identical therapeutic window as proposed in the clinical trial. This was confirmed through a neuropathological analysis, liver and kidney histopathology, detection of neutralizing antibodies, and systemic toxicities in the blood. Interestingly, we observed a significant survival advantage in rats with GBM receiving the 300 mg/day equivalent dosage of DOX versus the 200 mg/day equivalent. Additionally, rats rejected "recurrent" brain tumor threats implanted 90 days after their primary brain tumors. We also show that DOX detection within the plasma can be an indicator of optimal dosing of DOX to attain therapeutic levels. This work has significant clinical relevance for an ongoing phase I clinical trial in humans with primary GBM and for other therapeutic approaches using

  19. The influence of position deviation on RAIU and,the corresponding therapeutic dose calculations in patients with Graves hyperthyroidism

    Institute of Scientific and Technical Information of China (English)

    李从心

    2013-01-01

    Objective To evaluate the influence of inappropriate position deviation on radioactive iodine uptake(RAIU),effective half-life(Teff)and the corresponding dose variances in patients suffering from Graves hyperthyroidism.Methods RAIU was examined in 20 patients with

  20. Therapeutic Doses of Nonsteroidal Anti-Inflammatory Drugs Inhibit Osteosarcoma MG-63 Osteoblast-Like Cells Maturation, Viability, and Biomineralization Potential

    Directory of Open Access Journals (Sweden)

    E. De Luna-Bertos

    2013-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line were incubated in culture medium with 1–10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix.

  1. A simple dose regimen of artesunate and amodiaquine based on age or body weight range for uncomplicated falciparum malaria in children: comparison of therapeutic efficacy with standard dose regimen of artesunate and amodiaquine and artemether-lumefantrine.

    Science.gov (United States)

    Gbotosho, Grace O; Sowunmi, Akintunde; Okuboyejo, Titilope M; Happi, Christian T; Folarin, Onikepe O; Adewoye, Elsie O

    2012-07-01

    A new dose regimen of artesunate and amodiaquine (NDRAA) based on age or body weight range was compared with standard dose regimen of artesunate and amodiaquine (SDRAA) calculated according to body weight and with fixed-dose artesunate-amodiaquine (FDAA) and artemether-lumefantrine (AL) in 304 children afflicted by malaria aged 15 years or younger. In initial comparison (n = 208), children on NDRAA received 1-3 times amodiaquine per kilogram of body weight and 1-1.5 times of artesunate per kilogram of body weight compared with those receiving SDRAA. Parasite but not fever clearance was significantly faster in children who received NDRAA (19.4 ± 8.4 hours vs. 24.6 ± 15.5 hours, P = 0.003). Polymerase chain reaction-uncorrected cure rates on days 28-42 were also significantly higher in children who received NDRAA (P < 0.02 in all cases). Therapeutic responses in children younger than 5 years (n = 96) treated with NDRAA, FDAA, and AL were similar. Changes in hematocrit values and reported adverse events after commencing therapy were similar in those who received NDRAA and SDRAA. All drug regimens were well tolerated. NDRAA based on age or body weight range is simple, is therapeutically superior to SDRAA calculated according to body weight, and is as efficacious as AL in children younger than 5 years.

  2. Subacute Therapeutic Dosing of Artemether-Lumefantrine and Artesunate-Amodiaquine Combination Preserves Plasma Cholesterol, Renal Antioxidant Status, and Organ Weights in Rats

    Directory of Open Access Journals (Sweden)

    Chiagoziem A. Otuechere

    2012-01-01

    Full Text Available Recent instances of breakdowns of malaria control programs and the constant emergence of drug-resistant parasites to monotherapies have shored up the use of artemisinin-based combination therapy (ACT as the malaria therapy of choice. We evaluated a subacute therapeutic dosing of artemether-lumefantrine and artesunate-amodiaquine on plasma cholesterol, renal antioxidants, and organ weights in rats. Sixteen albino rats were grouped into three. Group A (n=5 served as the control. Groups B (n=6 and C (n=5 were administered, twice daily, oral therapeutic doses of artemether-lumefantrine (1.14/6.86 mg/kg/d and artesunate-amodiaquine (2.86/8.58 mg/kg/d, respectively, for seven days. From our results, ACTs did not significantly (P>0.05 alter catalase, superoxide dismutase, glutathione S-transferase, myeloperoxidase, and total glutathione levels when compared with the control. Plasma total cholesterol levels also decreased insignificantly (P>0.05. Organ-system weights were not significantly (P>0.05 different from control rats. Artesunate-amodiaquine, but not artemether-lumefantrine, significantly increased (P<0.05 lactate dehydrogenase activity and also afforded a 27.2% decrease in heart weight when compared with control. Also, both ACTs increased (P<0.05 lipid peroxidation. Overall, artesunate-amodiaquine and artemether-lumefantrine may preserve renal antioxidants and organ weights in vivo. However, caution is required above therapeutic indications or in chronic doses as this may predispose to renal oxidative stress.

  3. Pharmacist-managed dose adjustment feedback using therapeutic drug monitoring of vancomycin was useful for patients with methicillin-resistant Staphylococcus aureus infections: a single institution experience

    Science.gov (United States)

    Hirano, Ryuichi; Sakamoto, Yuichi; Kitazawa, Junichi; Yamamoto, Shoji; Tachibana, Naoki

    2016-01-01

    Background Vancomycin (VCM) requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP) on attaining target VCM trough concentrations and pharmacokinetics (PK)/pharmacodynamics (PD) parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Materials and methods The ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation) and from April 2012 to December 2014 (postimplementation), 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51). In 65 patients (pre, n=15; post, n=50), 24-hour area under the concentration–time curve (AUC 0–24 h)/minimum inhibitory concentration (MIC) ratios were calculated. Results Pharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33). The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL) was significantly higher during postimplementation (84%, 43/51) than during preimplementation (39%, 11/28) (P400) was significantly higher during postimplementation (84%, 42/50) than during preimplementation (53%, 8/15; P=0.013). There were no significant differences in nephrotoxicity or mortality rate. Conclusion Our ASP increased the percentage of patients that attained optimal VCM trough concentrations and PK/PD parameters, which contributed to the appropriate use of VCM in patients with MRSA infections. PMID:27789965

  4. A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

    Science.gov (United States)

    Li, Jun; Nekka, Fahima

    2013-02-21

    The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. PMID:23201275

  5. Nevirapine Exposure with WHO Pediatric Weight Band Dosing: Enhanced Therapeutic Concentrations Predicted Based on Extensive International Pharmacokinetic Experience

    NARCIS (Netherlands)

    Nikanjam, M.; Kabamba, D.; Cressey, T.R.; Burger, D.M.; Aweeka, F.T.; Acosta, E.P.; Spector, S.A.; Capparelli, E.V.

    2012-01-01

    Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used worldwide as part of combination antiretroviral therapy in infants and children to treat HIV infection. Dosing based on either weight or body surface area has been approved by the U.S. Food and Drug Administration (FDA)

  6. Assessment of absorbed dose and therapeutic response of tumor in repeated high-dose I-131 anti-CD20 monoclonal antibody (rituximab) radioimmunotherapy for non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Lim, Sang Moo; Kim, Kyeong Min [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2007-07-01

    We assessed the therapeutic dose absorbed to the tumor and response in repeated RIT with I-131 rituximab for NHL. Patients with NHL (n=6) were administered a therapeutic dose of I-131 rituximab (192.527.0 mCi). The number of repeated administration was 3 for all patients. Total 12 measurable tumor regions were assessed at the time of each RIT. Whole-body (WB) planar images with anterior and posterior views were acquired sequentially at 5 min, 5hr, 24hr, 48hr, and 72hr post-injection using gamma camera. F-18-FDG PET/CT was performed before (within 7 days) and after (on Day 30) RIT. From PET/CT image acquired before RIT, maximum intensity projection (MIP) image of coronal view was acquired. Serial WB planar images were overlaid to the coronal MIP PET image, respectively, by means of registration using 4 fiducial marks (bilateral shoulder and buttock) implemented in AMIDE software. On registered MIP PET and WB planar images, both 2D-ROIs were drawn on the region of tumor and background nearby tumor. The shape of 2D-ROI of tumor was determined from the MIP PET image. The volume of tumor was measured from the CT image, the % change of tumor volume before and after RIT was used in evaluation of the therapeutic response. The values of CT-based tumor volume were 8.216.3cc. The values of absorbed dose for tumor and the % changes of tumor volume before and after RIT were 231.8603.0rad, and 55.548.7%, respectively, and did not show the linear relationship (r=0.2787). The values of absorbed dose for tumor and the % changes of tumor volume did not correlate with the number of repeated administration (p>0.05, ANOVA). Aligning PET and planar images could estimate the quantitative values of absorbed dose to tumor. The data suggest that repeated RIT with I-131 rituximab is necessary for NHL, because single-RIT is insufficient to achieve remission of disease.

  7. Semiempirical model for diagnostication Helicobacter pylori infection by use of 14C labelled urea

    International Nuclear Information System (INIS)

    The main aim of this study was to create a semiempirical model, helpful in estimating severity of the Helicobacter pylori (H.pylori) infection by using the urea breath test (UBT), when urea labelled 14C has been used for diagnostics. The model consists of four compartments representing stomach (1), blood vascular system (2), lungs (3) and urinary system (4). Mathematical model is based on the balance of radioactive 14C in compartments from 1 to 4. The histological investigations were used as reference methods. Comparison of the results obtained from simulation, which yields dependence of 14C activity on time, to experimental results of UBT, made it possible to determine the ranges of coefficient HB value, which characterized each degrees of severity of H. pylori infection: degree 0 (lack of infection) - hB below 0.025; degree 1 (not large) - hB in range 0.025-0.115; degree 2 (moderate) - hB in the range 0.115-0.300; degree 3 (significant) - hB above 0.300. It was possible to estimate severity of H.pylori infection in clinical practice on the basis of comparing the 14C activity value of experimental points as obtained from the breath test, to the results of simulation with suitable value of the fitted parameter hB indicating degree of severity of infection. (author)

  8. Release of (14)C-labelled carbon nanotubes from polycarbonate composites.

    Science.gov (United States)

    Rhiem, Stefan; Barthel, Anne-Kathrin; Meyer-Plath, Asmus; Hennig, Michael P; Wachtendorf, Volker; Sturm, Heinz; Schäffer, Andreas; Maes, Hanna M

    2016-08-01

    Waste disposal of carbon nanotube (CNT) containing products is expected to be the most important pathway for release of CNTs into the environment. In the present work, the use of radiolabelled CNTs ((14)C-CNT) for polycarbonate polymer nanocomposites with 1 wt% (14)C-CNT content allowed for the first time to quantify and differentiate the CNT release according to the type of impact along the materials' ageing history. After an initial exposure of the nanocomposite by solar-like irradiation, further environmental impacts were applied to composite material. They aimed at mimicking disposal site conditions that may induce further ageing effects and CNT release. This study included shaking in water, rapid temperature changes, soaking in humic acid solution as well as waste water effluent, and, finally, gentle mechanical abrasion. All ageing impacts were applied sequentially, both on pristine (control) and on solar-irradiated nanocomposites. All experiments were accompanied by absolute quantification of radioactive release as well as chemical and morphological analyses of the nanocomposite surfaces using infra-red (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The morphological analysis showed that spectral irradiation can uncover CNT networks on the outer nanocomposite surface layers by polymer degradation. After having subjected the solar-irradiated nanocomposite to all studied disposal site effect, the total radioactive release was quantified to amount to 64 mg CNT/m(2), whereas only 0.8 mg CNT/m(2) were found for the un-irradiated control sample. Solar degradation of polymers was thus found to significantly increase the propensity of the studied polymer nanocomposites to release CNTs during ageing effects at the product's end-of-life typical for disposal sites. PMID:27194367

  9. Translocation of 14C-labelled photosynthetic assimilates in cassava (Manihot esculenta Crantz)

    International Nuclear Information System (INIS)

    Leaves of cassava (Manihot esculenta Crantz cv. Ankra) plants were allowed to assimilate 14CO2 in photosynthesis. Following labelling with 14C at six months of age, plants were harvested after seven days and after six months, near maturity. Additional plants were labelled at eight and twelve months of age and harvested immediately, after seven days, or near maturity. 14C in individual plant parts at each harvest was determined by liquid scintillation counting. Radioactive assimilates were recovered primarily in leaves exposed to 14CO2, in stems between these labelled leaves and the tubers, and in the tubers. All plants had two stems. Very little of the 14C assimilated by leaves on one stem was translocated into the other stem. Up to 60% of assimilated 14C went to the tubers when plants were growing rapidly. 14C assimilated during the dry season was recovered mainly in above-ground parts. Two separate estimates indicated that 40% of the assimilated 14C was lost in respiration and leaf abscission during the first week after labelling. (author)

  10. Biosynthesis of 14C-labelled erucic acid by means of rape plants

    International Nuclear Information System (INIS)

    For the biosynthetic preparation of 14C-erucic adid (C21H41COOH) by means of rape plants cv. sollux the plants were supplied with 14CO2 and additionally fed with 14C-Sodium acetate after anthesis. After saponification of the extracted lipids the erucic acid was isolated and purified. The substance was identified by gas chromatography. The incorporation of the applied radioactive (34 MBq 14CO2; 37 MBq 14C-natrium acetate) into the fatty acids amounted to 1,2 per cent. The erucic acid could be isolated from the fatty acids mixture with a specific radioactivity of 1,001 MBq/mmol and a purity of 97,2 per cent. (orig.)

  11. Some chemical synthesis of 14C labelled compounds of pharmaceutical or biological interest

    International Nuclear Information System (INIS)

    The recent discovery of the tuberculostatic properties of the hydrazide of isonicotinic acid (so-called 'Isoniazide', 'Rimifon') has raised considerably its interest, as for metabolic studies which it is more interesting to have it labelled with 14C. We describe in this report the chemical synthesis of 14C carboxyl labelled isoniazide which were done in the pyridine ring to highlight his metabolic function on the Koch's bacillus. (M.B.)

  12. Some chemical synthesis of {sup 14}C labelled compounds of pharmaceutical or biological interest

    Energy Technology Data Exchange (ETDEWEB)

    Pichat, I.; Baret, C.; Audinot, M.; Herbert, M.; Lambin, J. [Commissariat a l' Energie Atomique, Lab. du Fort de Chatillon, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1955-07-01

    The recent discovery of the tuberculostatic properties of the hydrazide of isonicotinic acid (so-called 'Isoniazide', 'Rimifon') has raised considerably its interest, as for metabolic studies which it is more interesting to have it labelled with {sup 14}C. We describe in this report the chemical synthesis of {sup 14}C carboxyl labelled isoniazide which were done in the pyridine ring to highlight his metabolic function on the Koch's bacillus. (M.B.)

  13. Nitrogen mustard derivated from adiphenine. Synthesis and 14C labelling. Antitumor activity and tissular distribution

    International Nuclear Information System (INIS)

    The synthesis of a new nitrogen mustard 14C is described. The compound is found to be active in intraperitoneal murine L 1210 and P 388 tumors. Preliminary tissue distribution studies after i.v. administration to rats and mice show that the mustard and/or its metabolites partially cross the blood-brain barrier

  14. Role of biotransformation, sorption and mineralization of (14)C-labelled sulfamethoxazole under different redox conditions.

    Science.gov (United States)

    Alvarino, T; Nastold, P; Suarez, S; Omil, F; Corvini, P F X; Bouju, H

    2016-01-15

    (14)C-sulfamethoxazole biotransformation, sorption and mineralization was studied with heterotrophic and autotrophic biomass under aerobic and anoxic conditions, as well as with anaerobic biomass. The (14)C-radiolabelled residues distribution in the solid, liquid and gas phases was closely monitored along a total incubation time of 190 h. Biotransformation was the main removal mechanism, mineralization and sorption remaining below 5% in all the cases, although the presence of a carbon source exerted a positive effect on the mineralization rate by the aerobic heterotrophic bacteria. In fact, an influence of the type of primary substrate and the redox potential was observed in all cases on the biotransformation and mineralization rates, since an enhancement of the removal rate was observed when an external carbon source was used as a primary substrate under aerobic conditions, while a negligible effect was observed under nitrifying conditions. In the liquid phases collected from all assays, up to three additional peaks corresponding to (14)C-radiolabelled residues were detected. The highest concentration was observed under anaerobic conditions, where two radioactive metabolites were detected representing each around 15% of the total applied radioactivity after 180 h incubation. One of the metabolites detected under anoxic and anaerobic conditions, is probably resulting from ring cleavage of the isoxazole ring. PMID:26546766

  15. A computerised sampling strategy for therapeutic drug monitoring of lithium provides precise estimates and significantly reduces dose-finding time

    DEFF Research Database (Denmark)

    Høgberg, Lotte Christine Groth; Jürgens, Gesche; Zederkof, Vivian Wederking;

    2012-01-01

    The clinical benefit of implementing Bayesian approach for lithium drug monitoring was evaluated. Intervention group (N = 42) and historical control group (N = 55) patients were each divided into two groups: Dosage with immediate-release lithium carbonate or a sustained-release formulation, lithium...... citrate. Bayesian approach was performed in the intervention groups, and estimation of lithium steady-state trough concentration was obtained from non-steady-state blood sample, collected about 12 hr after the first lithium study dose. The estimate was compared with the actually measured steady.......96 ± 11.24 days (mean ± S.D.) (p = 0.0003). Bayesian approach was an advantage for the clinicians as a fast and safe aid to obtain the optimal lithium treatment dose....

  16. Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model.

    Science.gov (United States)

    Gomis-González, Maria; Matute, Carlos; Maldonado, Rafael; Mato, Susana; Ozaita, Andrés

    2016-01-01

    Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS. PMID:27589806

  17. Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model

    Science.gov (United States)

    Gomis-González, Maria; Busquets-Garcia, Arnau; Matute, Carlos; Maldonado, Rafael; Mato, Susana; Ozaita, Andrés

    2016-01-01

    Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS. PMID:27589806

  18. Measurement of charged particle yields from therapeutic beams in view of the design of an innovative hadrontherapy dose monitor

    Science.gov (United States)

    Battistoni, G.; Bellini, F.; Bini, F.; Collamati, F.; Collini, F.; De Lucia, E.; Durante, M.; Faccini, R.; Ferroni, F.; Frallicciardi, P. M.; La Tessa, C.; Marafini, M.; Mattei, I.; Miraglia, F.; Morganti, S.; Ortega, P. G.; Patera, V.; Piersanti, L.; Pinci, D.; Russomando, A.; Sarti, A.; Schuy, C.; Sciubba, A.; Senzacqua, M.; Solfaroli Camillocci, E.; Vanstalle, M.; Voena, C.

    2015-02-01

    Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back γ s, produced in the positron annihilation from β + emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt γ s) performed at different beam and energies that have a particular relevance for PT applications: 12C beam of 80 MeV/u at LNS, 12C beam 220 MeV/u at GSI, and 12C, 4He, 16O beams with energy in the 50-300 MeV/u range at HIT. Finally, a project for a multimodal dose-monitor device exploiting the prompt photons and charged particles emission will be presented.

  19. Mechanistic and single-dose in vivo therapeutic studies of Cry5B anthelmintic action against hookworms.

    Directory of Open Access Journals (Sweden)

    Yan Hu

    Full Text Available BACKGROUND: Hookworm infections are one of the most important parasitic infections of humans worldwide, considered by some second only to malaria in associated disease burden. Single-dose mass drug administration for soil-transmitted helminths, including hookworms, relies primarily on albendazole, which has variable efficacy. New and better hookworm therapies are urgently needed. Bacillus thuringiensis crystal protein Cry5B has potential as a novel anthelmintic and has been extensively studied in the roundworm Caenorhabditis elegans. Here, we ask whether single-dose Cry5B can provide therapy against a hookworm infection and whether C. elegans mechanism-of-action studies are relevant to hookworms. METHODOLOGY/PRINCIPAL FINDINGS: To test whether the C. elegans invertebrate-specific glycolipid receptor for Cry5B is relevant in hookworms, we fed Ancylostoma ceylanicum hookworm adults Cry5B with and without galactose, an inhibitor of Cry5B-C. elegans glycolipid interactions. As with C. elegans, galactose inhibits Cry5B toxicity in A. ceylanicum. Furthermore, p38 mitogen-activated protein kinase (MAPK, which controls one of the most important Cry5B signal transduction responses in C. elegans, is functionally operational in hookworms. A. ceylanicum hookworms treated with Cry5B up-regulate p38 MAPK and knock down of p38 MAPK activity in hookworms results in hypersensitivity of A. ceylanicum adults to Cry5B attack. Single-dose Cry5B is able to reduce by >90% A. ceylanicum hookworm burdens from infected hamsters, in the process eliminating hookworm egg shedding in feces and protecting infected hamsters from blood loss. Anthelmintic activity is increased about 3-fold, eliminating >97% of the parasites with a single 3 mg dose (∼30 mg/kg, by incorporating a simple formulation to help prevent digestion in the acidic stomach of the host mammal. CONCLUSIONS/SIGNIFICANCE: These studies advance the development of Cry5B protein as a potent, safe single-dose

  20. Relationship of tumor absorbed doses of 177Lu-DOTA-TATE treatment and uptake in pre-therapeutic Ga68 DOTA-TATE PET/CT imaging

    International Nuclear Information System (INIS)

    Full text of publication follows. Introduction/Background: Peptide Receptor Radionuclide Therapy (PRRT) with labeled Lu177 labeled peptide in patients with neuroendocrine tumors (NETs) aroused great interest. An estimation of actual radiation doses to tumors is very important for therapy planning. It is well known that uptake of Ga-68 DOTATATE very well correlated with sst2 expression. The uptake of radio-labelled peptides calculated from SUV max values may predict the radiation-absorbed dosimetry of lesions treated with PRRT. Aim: the aim of the study was to evaluate the relationship between the tumor absorbed doses and pre-therapeutic Ga68 DOTA-TATE PET/CT uptake calculated from SUV values. Materials and methods: PRRT results of patients (M/F: 8/5, mean age: 55.5 ± 12.5 years) with histologically proven inoperable NETs were retrospectively analyzed. Dosimetric calculations were performed using MIRD scheme and lesion doses were calculated using post therapy whole body images obtained at 4, 20, 44, and 68 hours after injection. Calculated tumor absorbed doses were compared with SUVmax of 68Ga-DOTA-TATE PET/CT, which were performed before the therapy. Tumor volumes were determined from CT images. Thirteen blood samples beginning from time zero to 4 days after injection were obtained for bone marrow and whole body dosimetry. Results: there were 38 lesions in 13 patients. Lesions were selected according to lesion delineation and superimposed lesions were excluded. Mean lesion volume was 19.58 ± 25 cm3. Median tumor dose for all lesions, bone lesions, lesions on other sites (lung, liver, lymph nodes) were 15.08 Gy, 19.34 Gy, 14.05 Gy per 370 MBq respectively. Median SUVmax values of those were 25.8, 13.7, 23.05, respectively. Correlation between calculated tumor dose and uptake of 68Ga-DOTA-TATE was moderate (R=0.42). Also a moderate correlation was found for radiation absorbed doses of bone metastases. A very low correlation was found for radiation absorbed doses of

  1. Therapeutic Horseback Riding Outcomes of Parent-Identified Goals for Children with Autism Spectrum Disorder: An ABA' Multiple Case Design Examining Dosing and Generalization to the Home and Community

    Science.gov (United States)

    Holm, Margo B.; Baird, Joanne M.; Kim, Young Joo; Rajora, Kuwar B.; D'Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

    2014-01-01

    We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6-8 years…

  2. A case of Scalp Rosacea treated with low dose doxycycline and probiotic therapy and literature review on therapeutic options.

    Science.gov (United States)

    Fortuna, M C; Garelli, V; Pranteda, G; Romaniello, F; Cardone, M; Carlesimo, M; Rossi, A

    2016-07-01

    Rosacea is a common chronic inflammatory disorder showing a wide range of clinical features such as telangiectasia, erythema, papules, and pustules primarily involving the central part of face (forehead, cheeks and nose) although extra facial manifestation have been described. We describe a case of rosacea with predominant scalp involvement successfully treated with a 8-week-course of doxycycline 40 mg once a day and probiotic therapy twice a day (Bifidobacterium breve BR03, Lactobacillus salivarius LS01 1 × 10(9) UFC/dose). PMID:27087407

  3. Therapeutic cranial nerve irradiation: results from a multi-center dose response study of radiosurgery for trigeminal neuralgia

    International Nuclear Information System (INIS)

    Purpose/Objective: We performed a multi-institution study to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. We hypothesized that MRI-stereotactic targeting of the trigeminal nerve and irradiation with a single 4 mm isocenter, 2-4 mm anterior to the brainstem, could be a safe and effective treatment for this disorder. Materials and Methods: Fifty patients at five centers had radiosurgery using a single 4 mm isocenter targeted at the root entry zone. All patients had typical trigeminal neuralgia. The mean patient age was 70 years, (range, 40-87). Thirty-two patients had undergone prior surgery, and the mean number of procedures performed was 2.8 (range, 1-7). Eighteen patients (36%) had not had prior surgery before radiosurgery. Maximum radiosurgery doses included 60 Gy (n=8), 65 Gy (n=3), 70 Gy (n=27), 75 Gy (n=2), 80 Gy (n=6) and 90 Gy (n=4). All patients were discharged within 24 hours and were studied in regard to the degree of pain relief, latency interval to pain relief, sensory loss, and the need for further therapy. Mean follow-up after radiosurgery was 9.2 months (range, 2-26 months). Results: At last follow-up, 25 patients (50%) had excellent control (pain-free), 17 (34%) had good control (50-90% relief), and 8 (16%) had failed (see Figure). The median time to pain relief was one month. We identified an actuarial response rate of 53% for complete pain relief at seven months, and 93% for pain reduction (50-100% relief). At 18 months, these results declined to 48% and 77% respectively. A significantly greater proportion of patients receiving a radiosurgery maximum dose of ≥ 70 Gy achieved complete pain relief (63% vs. 18%) and >50% pain reduction (96% vs. 80%) than those with doses <70 Gy. Patients without prior surgery had significantly better outcomes in univariate testing. Three patients (6%) developed increased facial paresthesiae after radiosurgery

  4. Measurement of charged particle yields from therapeutic beams in view of the design of an innovative hadrontherapy dose monitor

    CERN Document Server

    Battistoni, G; Bini, F; Collamati, F; Collini, F; De Lucia, E; Durante, M; Faccini, R; Ferroni, F; Frallicciardi, P M; La Tessa, C; Marafini, M; Mattei, I; Miraglia, F; Morganti, S; Ortega, P G; Patera, V; Piersanti, L; Pinci, D; Russomando, A; Sarti, A; Schuy, C; Sciubba, A; Senzacqua, M; Solfaroli Camillocci, E; Vanstalle, M; Voena, C

    2015-01-01

    Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back γ s, produced in the positron annihilation from β + emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt γ s) performed at different beam and energies that have a particular relevan...

  5. Therapeutic efifcacy and bone marrow protection of the mdr1 gene and over-dose chemotherapy with doxorubicin for rabbits with VX2 hepatocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yi Wang; Xian-Qing Jin; Shan Wang; Qiao Wang; Qing Luo; Xiao-Ji Luo

    2006-01-01

    BACKGROUND: Malignant tumors are common diseases threatening to the health and life of human being. Clinically, the multidrug resistance of tumor cells and bone marrow depression caused by chemotherapeutic agents are the main obstacles to the treatment of tumors, and both are related to the mdr1 gene. The over expression of the mdr1 gene in tumor cells contributes to the multidrug resistance of malignant tumor cells. With little expression of the mdr1 gene, bone marrow cells particularly susceptible to multidrug resistance-sensitive agents, which cause serious toxicity in bone marrow. This study was undertaken to assess therapeutic efifcacy of transplantation of bone marrow mononuclear cells transferred with the mdr1 gene and over-dose chemotherapy with doxorubicin for VX2 hepatocarcinoma of rabbits. METHODS: The mdr1 gene was transferred into the bone marrow mononuclear cells of rabbits, which was co-cultured with retroviral vector-containing supernatant, and the cells were autotransplanted into a rabbit model with VX2 hepatocarcinoma. After chemotherapy with doxorubicin, the protective effects of the mdr1 gene and therapeutic efifcacy of over-dose chemotherapy were observed. RESULTS:The mdr1 gene was transferred successfully into the bone marrow mononuclear cells, with a transduction efifciency of 35%. After autotransplantation, the mdr1 gene was expressed functionally in bone marrow with a positive rate of 8%, indicating that the gene played an important role in bone marrow protection. The rabbits with VX2 hepatocarcinoma, which had received the mdr1 gene-transduced cells, survived after chemotherapy with a 3-fold dose of adriamycin, and their white blood cell counts were (4.26±1.03)×104/L. Since hepatocarcinoma cells were eradicated, the survival time (97.00±46.75 d) of the rabbits was extended (P CONCLUSIONS:The transferring of the mdr1 gene into bone marrow mononuclear cells could confer chemoprotection to bone marrow, and over-dose chemotherapy could be

  6. Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance antiretroviral therapy with the guidance of therapeutic drug monitoring

    Directory of Open Access Journals (Sweden)

    Shang-Ping Yang

    2014-11-01

    Full Text Available Introduction: Wide inter-patient variation of plasma efavirenz (EFV concentrations has been observed, and a substantial proportion of HIV-positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV-containing combination antiretroviral therapy (cART at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM-guided strategy to optimize the EFV dose in HIV-positive Taiwanese patients. Materials and Methods: The plasma EFV concentrations at 12 hours (C12 after taking the previous dose were determined among HIV-positive adults who had received EFV-containing cART with viral suppression (plasma HIV RNA load (PVL 2.0 mg/L, EFV (Stocrit, MSD was reduced to half a tablet daily. Determinations of EFV C12 were repeated 4–12 weeks after switch using high-performance liquid chromatography. CYP2B6 G516T polymorphisms were determined using polymerase-chain-reaction restriction fragment-length polymorphism. Results: Between April 2013 and June 2014, 111 patients (95.5% male; mean age, 39 years; 96.4% with PVL 2.0 mg/L were switched to a reduced dose (1/2# hs of EFV; 45.5% of them had CYP2B6 G516T or TT genotypes; and 32.4% weighed 60 kg or less. The mean baseline EFV C12 before switch was 3.65 mg/L (interquartile range (IQR, 2.62–4.17 for 111 patients, which decreased to 1.96 mg/L (IQR, 1.53–2.33 for 64 patients who had completed follow-up of C12 EFV 4 weeks after switch, with a reduction of 49.4% (IQR, 38.9–57.0%. As of 10 July, 2014, all of the 38 patients (100% who had completed at least one follow-up of PVL achieved undetectable PVL (<40 copies/ml following switch to a reduced dose of EFV after a mean observation of 13 weeks

  7. Therapeutic horseback riding outcomes of parent-identified goals for children with autism spectrum disorder: an ABA' multiple case design examining dosing and generalization to the home and community.

    Science.gov (United States)

    Holm, Margo B; Baird, Joanne M; Kim, Young Joo; Rajora, Kuwar B; D'Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

    2014-04-01

    We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6-8 years of age participated, and counts of target behaviors were collected in each setting and phase of the study. Compared to Baseline, 70% of the target behaviors were better during Intervention and improvement was retained in 63% of the behaviors during Withdrawal. Increased doses of therapeutic riding were significant for magnitude of change, and the effect of the therapeutic riding sessions generalized to home and community. PMID:24091469

  8. SU-E-J-08: Comparison of Unintended Radiation Doses to Organs at Risk Resulting From the Out-Of-Field Therapeutic Beams and From Image-Guidance X-Ray Procedures

    Energy Technology Data Exchange (ETDEWEB)

    Ding, G; Wang, L [Vanderbilt University, Nashville, TN (United States)

    2015-06-15

    Purpose: The unintended radiation dose to organs at risk (OAR) can be contributed from imaging guidance procedures as well as from leakage and scatter of therapeutic beams. This study compares the imaging dose with the unintended out-of-field therapeutic dose to patient sensitive organs. Methods: The Monte Carlo EGSnrc user codes, BEAMnrc and DOSXYZnrc, were used to simulate kV X-ray sources from imaging devices as well as the therapeutic IMRT/VMAT beams and to calculate doses to target and OARs on patient treatment planning CT images. The accuracy of the Monte Carlo simulations was benchmarked against measurements in phantoms. The dose-volume histogram was utilized in analyzing the patient organ doses. Results: The dose resulting from Standard Head kV-CBCT scans to bone and soft tissues ranges from 0.7 to 1.1 cGy and from 0.03 to 0.3 cGy, respectively. The dose resulting from Thorax scans on the chest to bone and soft tissues ranges from 1.1 to 1.8 cGy and from 0.3 to 0.6 cGy, respectively. The dose resulting from Pelvis scans on the abdomen to bone and soft tissues range from 3.2 to 4.2 cGy and from 1.2 to 2.2 cGy, respectively. The out-of-field doses to OAR are sensitive to the distance between the treated target and the OAR. For a typical Head-and-Neck IMRT/VMAT treatment the out-of-field doses to eyes are 1–3% of the target dose, or 2–6 cGy per fraction. Conclusion: The imaging doses to OAR are predictable based on the imaging protocols used when OARs are within the imaged volume and can be estimated and accounted for by using tabulated values. The unintended out-of-field doses are proportional to the target dose, strongly depend on the distance between the treated target and OAR, and are generally higher comparing to the imaging dose. This work was partially supported by Varian research grant VUMC40590.

  9. SU-E-J-08: Comparison of Unintended Radiation Doses to Organs at Risk Resulting From the Out-Of-Field Therapeutic Beams and From Image-Guidance X-Ray Procedures

    International Nuclear Information System (INIS)

    Purpose: The unintended radiation dose to organs at risk (OAR) can be contributed from imaging guidance procedures as well as from leakage and scatter of therapeutic beams. This study compares the imaging dose with the unintended out-of-field therapeutic dose to patient sensitive organs. Methods: The Monte Carlo EGSnrc user codes, BEAMnrc and DOSXYZnrc, were used to simulate kV X-ray sources from imaging devices as well as the therapeutic IMRT/VMAT beams and to calculate doses to target and OARs on patient treatment planning CT images. The accuracy of the Monte Carlo simulations was benchmarked against measurements in phantoms. The dose-volume histogram was utilized in analyzing the patient organ doses. Results: The dose resulting from Standard Head kV-CBCT scans to bone and soft tissues ranges from 0.7 to 1.1 cGy and from 0.03 to 0.3 cGy, respectively. The dose resulting from Thorax scans on the chest to bone and soft tissues ranges from 1.1 to 1.8 cGy and from 0.3 to 0.6 cGy, respectively. The dose resulting from Pelvis scans on the abdomen to bone and soft tissues range from 3.2 to 4.2 cGy and from 1.2 to 2.2 cGy, respectively. The out-of-field doses to OAR are sensitive to the distance between the treated target and the OAR. For a typical Head-and-Neck IMRT/VMAT treatment the out-of-field doses to eyes are 1–3% of the target dose, or 2–6 cGy per fraction. Conclusion: The imaging doses to OAR are predictable based on the imaging protocols used when OARs are within the imaged volume and can be estimated and accounted for by using tabulated values. The unintended out-of-field doses are proportional to the target dose, strongly depend on the distance between the treated target and OAR, and are generally higher comparing to the imaging dose. This work was partially supported by Varian research grant VUMC40590

  10. The value of population pharmacokinetics and simulation for postmarketing safety evaluation of dosing guidelines for drugs with a narrow therapeutic index: buflomedil as a case study.

    Science.gov (United States)

    Bourguignon, Laurent; Ducher, Michel; Matanza, David; Bleyzac, Nathalie; Uhart, Mathieu; Odouard, Emmanuel; Maire, Pascal; Goutelle, Sylvain

    2012-04-01

    Population pharmacokinetics and simulation techniques currently play an important role in new drug development. This paper illustrates the potential value of those methods in postmarketing safety assessment, using buflomedil in elderly patients as an example. We retrospectively assessed the risk of buflomedil overdosing associated with the latest dosing recommendations of the French Drug Agency (AFSSAPS). First, buflomedil concentrations measured in 24 elderly patients were analysed with a nonparametric population approach. Then, the pharmacokinetic model was used to perform a 1000-patient Monte Carlo simulation for the two recommended buflomedil dosage regimens. The maximum concentrations calculated after 10 days of therapy were compared with levels observed in reported cases of toxicity to assess the probability of overdosing. A three-compartment model best fit concentration data. Population predictions showed little bias (-0.14 mg/L) and good precision (8.73 mg(2) /L(2)). Overall results of the simulation study showed that the application of the two recommended dosage regimens of buflomedil was associated with overdosing (C(max) > 10 mg/L) and potential toxicity in 2.9% of geriatric patients. In patients with mild renal impairment, who may receive the higher-dosage regimen by therapeutic error, the probability of overdosing was 6.2%. Despite specific dosing recommendations in case of renal impairment, this study shows that the use of buflomedil could be associated with significant risk of overdosing in geriatric patients. Such results might have enhanced decision-making when buflomedil safety was reassessed by AFSSAPS in 2006. The retrospective case of buflomedil illustrates how these methods may be valuable in postmarketing safety evaluation of potentially toxic drugs.

  11. On the preparation of a therapeutic dose of 177Lu-labeled DOTA-TATE using indigenously produced 177Lu in medium flux reactor

    International Nuclear Information System (INIS)

    177Lu could be produced with a specific activity of ∼23,000 mCi/mg (850 GBq/mg) by neutron activation using enriched 176Lu (64.3%) target when irradiation was carried out at a thermal neutron flux of 1x1014 n/cm2/s for 21 d. 177Lu-DOTA-TATE could be prepared in high radiochemical yield (∼99%) and adequate stability using the 177Lu produced indigenously. The average level of radionuclidic impurity burden in 177Lu due to 177mLu was found to be 250 nCi of 177mLu/1 mCi of 177Lu (9.25 kBq/37 MBq) at the end of bombardment, which corresponds to 0.025% of the total activity produced. The maximum specific activity achievable via careful optimization of the irradiation parameters was found to be adequate for the preparation of a therapeutic dose of the radiopharmaceutical. The in-house preparation of this agent using 25 μg (17.41 nmole) of DOTA-TATE and indigenously produced 177Lu (0.8 μg, 4.52 nmole), corresponding to peptide/Lu ratio of 3.85 yielded 98.7% complexation. Allowing possibility of decay due to transportation to users, it has been possible to demonstrate that at our end, a single patient dose of 150-200 mCi (5.55-7.40 GBq) can be prepared by using 250-333 μg of DOTA-TATE conjugate. This amount compares well with 177Lu-DOTA-TATE prepared for a typical peptide receptor radionuclide therapy (PRRT) procedure which makes use of 100 μg of the DOTA-TATE conjugate, which incorporates 50 mCi (1.85 GBq) of 177Lu activity, thereby implying that in order to achieve a single patient dose of 150-200 mCi (5.55-7.40 GBq), 300-400 μg of the conjugate needs to be used

  12. Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Se Hun; Na, Chang Ju; Kim, Jeong Hun; Han, Yeon Hee; KIm, Hee Kwon; Jeong, Hwan Jeong; Sohn, Myung Hee; Lim, Seok Tae [Dept. of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2015-06-15

    High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

  13. Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

    International Nuclear Information System (INIS)

    High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

  14. Determination of the best application time of 2,4-D 14C-labelled herbicides and 14C-labelled glyphosate for translocation to the root system of Glycyrrhiza Glabra vegetative growth stage

    International Nuclear Information System (INIS)

    In this research work, four different growth stages of Glycyrrhiza Glabra were studied separately and under green house conditions, and in all of these stages the plants were treated by labelled herbicides 14C-2,4-D and 14C-Glyphosate through the ad axial surface with activity of 0.60μci up to 0.1018 μci (in each 10μLi of solution). The plants were harvested 72 hours after treatment. They were divided into treated leaf, leaves and stem above the treated leaf and leaves and stem below the treated leaf and root. The amount of radio labelled herbicides in each homo genus solution (produced from extraction of herbicides from plants samples) was quantified using liquid scintillation counter. The amount of herbicide mobility and transfer to different parts of Glycyrrhiza Glabra in each growth stage were determined. This study shows that the best application time of 2,4-D for translocation to the root system of the plant is at 6- leaf stage, and 2,4-D indicates more trans loc ability as compared with Glyphosate

  15. Comparison of depth-dose distributions of proton therapeutic beams calculated by means of logical detectors and ionization chamber modeled in Monte Carlo codes

    Science.gov (United States)

    Pietrzak, Robert; Konefał, Adam; Sokół, Maria; Orlef, Andrzej

    2016-08-01

    The success of proton therapy depends strongly on the precision of treatment planning. Dose distribution in biological tissue may be obtained from Monte Carlo simulations using various scientific codes making it possible to perform very accurate calculations. However, there are many factors affecting the accuracy of modeling. One of them is a structure of objects called bins registering a dose. In this work the influence of bin structure on the dose distributions was examined. The MCNPX code calculations of Bragg curve for the 60 MeV proton beam were done in two ways: using simple logical detectors being the volumes determined in water, and using a precise model of ionization chamber used in clinical dosimetry. The results of the simulations were verified experimentally in the water phantom with Marcus ionization chamber. The average local dose difference between the measured relative doses in the water phantom and those calculated by means of the logical detectors was 1.4% at first 25 mm, whereas in the full depth range this difference was 1.6% for the maximum uncertainty in the calculations less than 2.4% and for the maximum measuring error of 1%. In case of the relative doses calculated with the use of the ionization chamber model this average difference was somewhat greater, being 2.3% at depths up to 25 mm and 2.4% in the full range of depths for the maximum uncertainty in the calculations of 3%. In the dose calculations the ionization chamber model does not offer any additional advantages over the logical detectors. The results provided by both models are similar and in good agreement with the measurements, however, the logical detector approach is a more time-effective method.

  16. Modeling vertical movement of organic matter in a soil incubated for 41 years with "1"4C labeled straw

    DEFF Research Database (Denmark)

    Bruun, S.; Christensen, B.T.; Thomsen, I.K.;

    2007-01-01

    The distribution of organic matter (OM) in the soil profile reflects the balance between inputs and decomposition at different depths as well as transport of OM within the profile. In this study we modeled movement of OM in the soil profile as a result of mechanisms resulting in dispersive...

  17. Calibration and validation of the 14C-labelled polyethylene glycol-binding assay for tannins in tropical browse

    International Nuclear Information System (INIS)

    This study evaluates the radiolabelled polyethylene glycol (PEG)-binding procedure [Silanikove, N., Shinder, D., Gilboa, N., Eyal, M., Nitsan, Z., 1996. Polyethylene glycol-binding to plant samples as an assay for the biological effects of tannins: predicting the negative effects of tannins in Mediterranean browse on rumen degradation. J. Agric. Food Chem. 44, 3230-3234] for tannin analysis, using 27 tropical browse plants. In this method, the amount of PEG bound to a plant sample is assumed to be a reflection of its tannin content. The method was modified to exclude the use of non-tanniniferous substrate for estimating non-specific binding (NSB) in tannin-containing substrates. Non-specific binding values varied widely (0.4-2.8 mg PEG/100 mg DM tannin-free substrate) when the tannin-free substrate was changed from wheat straw to either rye grass or maize shoots. We therefore propose a modified radiolabelled PEG-binding method to estimate the level of PEG-binding (PEGb) to tannin-containing foliage without using tannin-free substrate to correct for non-specific binding. In this approach, incremental levels of each tanniniferous substrate were used to generate PEGb values. The resultant linear response was analysed and tannin activity was expressed as the slope of the response curve (PEGbSlope) observed for each substrate. The slope takes into account the non-specific binding in each substrate, thus PEGbSlope does not require correction for NSB using tannin-free samples. This approach improved the correlation between PEGb and the 125I-labelled bovine serum albumin precipitation assay. Relationships between the modified PEG-binding assay and radiolabelled bovine serum albumin assay, in vitro tannin bioassay and colorimetric assays are presented. (author)

  18. Whole-body distribution of {sup 14}C-labeled silica nanoparticles and submicron particles after intravenous injection into Mice

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Nobumitsu, E-mail: sakai@risk.env.kyoto-u.ac.jp; Takakura, Masato; Imamura, Harutoshi [Kyoto University, Division of Environmental Engineering, Graduate School of Engineering (Japan); Sugimoto, Miki [Kyoto University, Division of Applied Biosciences, Graduate School of Agriculture (Japan); Matsui, Yasuto [Kyoto University, Division of Environmental Engineering, Graduate School of Engineering (Japan); Miyoshi, Hirokazu [University of Tokushima, Radioisotope Research Center (Japan); Nakayama, Aki; Yoneda, Minoru [Kyoto University, Division of Environmental Engineering, Graduate School of Engineering (Japan)

    2012-05-15

    We analyzed the whole-body distribution of {sup 14}C-ADP-labeled silica nanoparticles ({sup 14}C-ADP-SiO{sub 2} nanoparticles) and submicron particles ({sup 14}C-ADP-SiO{sub 2} submicron particles) after intravenous injection into ICR mice. The {sup 14}C-ADP-SiO{sub 2} nanoparticles and submicron particles were synthesized before the injection and the particle size was 19.6 and 130 nm, respectively. Similarly, the shape was spherical and the crystallinity was amorphous. After the synthesis, we injected mice with the {sup 14}C-ADP-SiO{sub 2} nanoparticles or the {sup 14}C-ADP-SiO{sub 2} submicron particles and dissected tissues after 1, 2, 4, 8 and 24 h. The radioactivity in the tissues was measured with a liquid scintillation counter. As a result, the retention percentage in bone, skin, lymph nodes, and the digestive mixture was at least twofold higher in the {sup 14}C-ADP-SiO{sub 2} nanoparticles-exposed mice, whereas the retention percentage in the kidney was statistically higher in the {sup 14}C-ADP-SiO{sub 2} submicron particles-exposed mice. Both types of {sup 14}C-ADP-SiO{sub 2} particles mainly translocated to the muscle, bone, skin, and liver, but hardly translocated to the brain and olfactory bulb. Furthermore, the {sup 14}C-ADP-SiO{sub 2} nanoparticles had a higher retention percentage (62.4 %) in the entire body at 24-h post-injection than did the {sup 14}C-ADP-SiO{sub 2} submicron particles (50.7 %). Therefore, we suggested that the {sup 14}C-ADP-SiO{sub 2} nanoparticles might be more likely than the {sup 14}C-ADP-SiO{sub 2} submicron particles to be retained in the body, and consequently they might be gradually accumulated by chronic exposure.

  19. New synthesis of carbamate, thiocarbamate and urea type herbicides: preparation of 14C-labelled diuron and EPTC

    International Nuclear Information System (INIS)

    N,N-dialkyl-carbamic acid-trimethylsilyl-esters were synthesized starting with 14CO2. The new synthesis route is simple and provides good radiochemical yield. Silyl-carbaminates directly or through carbamoyl-halogenides may be used for preparation of labelled herbicides: carbamates, thiocarbamates and ureas. (author)

  20. Synthesis and evaluation of [{sup 14}C]-Labelled and fluorescent-Tagged paclitaxel derivatives as new biological probes

    Energy Technology Data Exchange (ETDEWEB)

    Rao, C.S.; Chu, J.-J.; Lai, Y.-K. [Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan (China); Liu, R.-S. [Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan (China)

    1998-11-01

    Our present report deals with the preparation of hitherto unreported 7-([carbonyl-{sup 14}C]-acetyl)paclitaxel 4 and two new bioactive 7-substituted fluorescent taxoids (FITC 9 and rhodamine 11), as well as evaluation towards their applications as biological probes. The results in this report demonstrate that (a) the new paclitaxel derivatives 4, 9, 11 could be prepared with good yields starting from paclitaxel; (b) the [{sup 14}C]acetylation step was found to be better by using [{sup 14}C]acetic anhydride rather than [{sup 14}C]sodium acetate; (c) the radiochemical purity of 4 was 96% and its specific activity was 48 mCi/mmol; (d) the cytotoxicity of 4 was close to that of paclitaxel whereas 9, 11 were far less active than paclitaxel, but these cytotoxic levels were good enough for their biological applications; (e) the drug-quantitation by flow cytometric analysis using 9 and 11 was proved to be equally efficient with respect to the radioactivity-based determination employing 4; (f) the intracellular fluorescence mapping by 9 and 11 was found to be effective and the microtubule network pattern was visible in both the cases; (g) the overall fluorescence imaging efficiency was better with 11 while the intensity of fluorescence was higher with 9; (h) staining of nucleolus was observed in fluorescence studies of both 9 and 11. Based on these results, the newly prepared paclitaxel derivatives can be considered as efficient biological probes and should find further use in relevant applications. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  1. Binding of 14C-labeled food mutagens (IQ, MeIQ, MeIQx) by dietary fiber in vitro

    International Nuclear Information System (INIS)

    Binding of three mutagens, known to occur in fried or broiled foods, by thirteen different types of dietary fiber was investigated in vitro. Nonspecific binding by other food polymers was minimized by using protease and amylase treatment. Water-insoluble fiber components were responsible for most of the binding capacity. Generally, a slightly larger proportion of 2-amino-3,4-dimethylimidazo [4,5-f]quinoline (MeIQ) than of 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo] -4,5-f]quinoxaline (MeIQx) was bound. There was a significant correlation between Klason lignin content and binding of mutagens. Optimum pH for binding was between 4 and 6. Dietary fiber from sorghum had the highest binding capacity, which could be due to the presence of a large Klason lignin fraction

  2. /sup 14/C-labelled propoxur metabolic studies on Anopheles Stephensi from the south coast of Iran

    Energy Technology Data Exchange (ETDEWEB)

    Hossaini, M.A.; Manouchehri, A.V.; Zareh, Z. (Atomic Energy Organization of Iran, Teheran. Nuclear Research Centre)

    1984-08-01

    /sup 14/C-propoxur (Baygonsub(circled R)) was synthesized through the reaction of o-isopropoxyphenol with methyl isocyanate-/sup 14/C. The product was isolated chromatographically on Florisil and crystallized from carbon tetrachloride. The purity and structure were confirmed using infrared spectra, melting point, co-chromatography of Florisil column, and silica-gel G thin-layer chromatography. The purity was found to be at least 99%. The rate of absorption and other characteristics of /sup 14/C-propoxur resistance in Anopheles Stephensi from the south coast of Iran was investigated. The mortality of strain adults was 100% after a one hour exposure when 1 ppm /sup 14/C-propoxur was used. Moreover, the mortality was not changed when a lower concentration (5 ppm) was used. On the other hand, the absorbance of /sup 14/C-propoxur in several strains of A. Stephensi has been determined. The identity and TLC characteristics of products formed after 1 and 2 hours exposure, resp., to /sup 14/C-propoxur have also been investigated. 5 refs.

  3. Relocation of carbon from decomposition of {sup 14}C-labelled needle and fine root litter in peat soil

    Energy Technology Data Exchange (ETDEWEB)

    Domish, T.; Laine, J.; Laiho, R. [Helsinki Univ. (Finland). Dept. of Forest Ecology; Finer, L. [Finnish Forest Research Inst. (Finland). Joensuu Research Station; Karsisto, M. [Finnish Forest Research Inst. (Finland). Dept. of Forest Ecology

    1996-12-31

    Drainage of peatlands promotes a shift of biomass and production from the ground vegetation to the trees. Thus, the above-ground (e.g. needles) and below-ground (roots) litter production of trees increases. Fine roots in particular are an important factor in the carbon and nutrient cycle in forest ecosystems. A major part of the annual net primary production of trees may be allocated below ground, the relative proportion being smaller on fertile sites than on less fertile ones. For modelling the carbon balance of drained peatlands, it is important to know the fate of carbon from newly introduced and decomposing litter. Newly added and fertilised tree litter material may be decomposed at a rate different than litter from the ground vegetation. The objectives of this study are to study the pathways of decomposing litter carbon in peat soil and to evaluate the use of the litterbag method in a controlled environment. (9 refs.)

  4. Calibration and validation of the {sup 14}C-labelled polyethylene glycol-binding assay for tannins in tropical browse

    Energy Technology Data Exchange (ETDEWEB)

    Mlambo, V. [Animal Production Unit, FAO/IAEA Agriculture and Biotechnology Laboratory, Seibersdorf (Austria)]. E-mail: vmlambo@agric.uniswa.sz; Makkar, H.P.S. [Animal Production and Health Section, Joint FAO/IAEA Division of Nuclear Techniques in Agriculture and Food, International Atomic Energy Agency, Vienna (Austria)

    2005-08-19

    This study evaluates the radiolabelled polyethylene glycol (PEG)-binding procedure [Silanikove, N., Shinder, D., Gilboa, N., Eyal, M., Nitsan, Z., 1996. Polyethylene glycol-binding to plant samples as an assay for the biological effects of tannins: predicting the negative effects of tannins in Mediterranean browse on rumen degradation. J. Agric. Food Chem. 44, 3230-3234] for tannin analysis, using 27 tropical browse plants. In this method, the amount of PEG bound to a plant sample is assumed to be a reflection of its tannin content. The method was modified to exclude the use of non-tanniniferous substrate for estimating non-specific binding (NSB) in tannin-containing substrates. Non-specific binding values varied widely (0.4-2.8 mg PEG/100 mg DM tannin-free substrate) when the tannin-free substrate was changed from wheat straw to either rye grass or maize shoots. We therefore propose a modified radiolabelled PEG-binding method to estimate the level of PEG-binding (PEGb) to tannin-containing foliage without using tannin-free substrate to correct for non-specific binding. In this approach, incremental levels of each tanniniferous substrate were used to generate PEGb values. The resultant linear response was analysed and tannin activity was expressed as the slope of the response curve (PEGbSlope) observed for each substrate. The slope takes into account the non-specific binding in each substrate, thus PEGbSlope does not require correction for NSB using tannin-free samples. This approach improved the correlation between PEGb and the {sup 125}I-labelled bovine serum albumin precipitation assay. Relationships between the modified PEG-binding assay and radiolabelled bovine serum albumin assay, in vitro tannin bioassay and colorimetric assays are presented. (author)

  5. A Systems Biology Approach in Therapeutic Response Study for Different Dosing Regimens—a Modeling Study of Drug Effects on Tumor Growth using Hybrid Systems

    OpenAIRE

    Xiangfang Li; Lijun Qian; Bittner, Michale L.; Dougherty, Edward R.

    2012-01-01

    Motivated by the frustration of translation of research advances in the molecular and cellular biology of cancer into treatment, this study calls for cross-disciplinary efforts and proposes a methodology of incorporating drug pharmacology information into drug therapeutic response modeling using a computational systems biology approach. The objectives are two fold. The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical...

  6. Correlation of the MIC and dose/MIC ratio of fluconazole to the therapeutic response of patients with mucosal candidiasis and candidemia.

    NARCIS (Netherlands)

    Rodriguez-Tudela, J.L.; Almirante, B.; Rodriguez-Pardo, D.; Laguna, F.; Donnelly, J.P.; Mouton, J.W.; Pahissa, A.; Cuenca-Estrella, M.

    2007-01-01

    We report on the correlation of the outcomes for two cohorts of patients who had been treated for candidemia (126 episodes) or oropharyngeal candidiasis (110 episodes) with various doses of fluconazole and the MIC of fluconazole obtained by using the EUCAST standard for fermentative yeasts. Of 145 e

  7. Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses

    International Nuclear Information System (INIS)

    18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT. Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12). No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 ± 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial. This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously

  8. Initial dosing regimen of vancomycin to achieve early therapeutic plasma concentration in critically ill patients with MRSA infection based on APACHE II score.

    Science.gov (United States)

    Imaura, Masaharu; Yokoyama, Haruko; Kohata, Yuji; Kanai, Riichiro; Kohyama, Tomoki; Idemitsu, Wataru; Maki, Yuichi; Igarashi, Takashi; Takahashi, Hiroyuki; Kanno, Hiroshi; Yamada, Yasuhiko

    2016-06-01

    It is essential to assure the efficacy of antimicrobials at the initial phase of therapy. However, increasing the volume of distribution (Vd) of hydrophilic antimicrobials in critically ill patients leads to reduced antimicrobial concentration in plasma and tissue, which may adversely affect the efficacy of that therapy. The aim of the present study was to establish a theoretical methodology for setting an appropriate level for initial vancomycin therapy in individual patients based on Acute Physiology and Chronic Health Evaluation (APACHE) II score. We obtained data from patients who received intravenous vancomycin for a suspected or definitively diagnosed Gram-positive bacterial infection within 72 h after admission to the intensive care unit. The Vd and elimination half-life (t 1/2) of vancomycin values were calculated using the Bayesian method, and we investigated the relationship between them and APACHE II score. There were significant correlations between APACHE II scores and Vd/actual body weight (ABW), as well as t 1/2 (r = 0.58, p < 0.05 and r = 0.74, p < 0.01, respectively). Our results suggested that the Vd and t 1/2 of vancomycin could be estimated using the following regression equations using APACHE II score.[Formula: see text] [Formula: see text]We found that APACHE II score was a useful index for predicting the Vd and t 1/2 of vancomycin, and used that to establish an initial vancomycin dosing regimen comprised of initial dose and administration interval for individual patients.

  9. Treatment with high dose [111In-DTPA-D-PHE1]-octreotide in patients with neuroendocrine tumors. Evaluation of therapeutic and toxic effects

    International Nuclear Information System (INIS)

    Carcinoid tumors and endocrine pancreatic tumors often express somatostatin receptors (sst). Tumor spread may be visualized by sst scintigraphy using [111In-DTPA-D-Phe1]-octreotide. In this study, tumor targeting therapy with [111In-DTPA-D-Phe1]-octreotide at high doses (6 GBq every third week) was used to treat patients with sst-expressing tumors. Five patients entered the protocol and three were evaluable for response, while all could be evaluated for toxicity. Two patient responded with a significant reduction in tumor markers (> 50%). The third patient showed increasing levels of tumor markers. Side effects were expressed as depression of bone-marrow function. In one patient a grade 4 reduction in platelet count was observed requiring several thrombocyte transfusions. In another two patients platelet counts decreased significantly. We conclude that treatment with [111In-DTPA-D-Phe1]-octreotide can be used in patients with neuroendocrine tumors but blood parameters have to be carefully monitored to avoid severe side effects. (orig.)

  10. Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

    Directory of Open Access Journals (Sweden)

    Owain Thomas

    Full Text Available Low molecular weight heparins (LMWH's are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa, activated partial thromboplastin time (aPTT and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.To examine the effects of two different LMWH's on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests' concordance.Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR and Hemochron Jr (HCJ and an optical plasma method using two different reagents (ActinFSL and PTT-Automat. Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.Methods' mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11 and 69s (SD 14 for enoxaparin and between 101s (SD 21 and 140s (SD 28 for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62-0.87, whereas the other aPTT methods had similar correlation coefficients (Rs0.80-0.92.aPTT displays a linear dose-response to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa's present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH's.

  11. Therapeutic drug monitoring, a practical application

    NARCIS (Netherlands)

    Kees Neef, C.; Touw, D.J.

    2010-01-01

    Therapeutic Drug Monitoring (TDM) is an indispensable tool in therapeutic handling and medication safety. A definition of TDM is: Therapeutic drug monitoring is a system of quality assurance of a drug management system, aiming that the right drug is given tot the right patient in the right dose in o

  12. 131I治疗青少年Graves病的量效分析%An analysis of the dose and the therapeutic effect of 131I in treating youngsters with Graves disease

    Institute of Scientific and Technical Information of China (English)

    李佳; 秦岚; 任众; 张又萍

    2010-01-01

    .22-2.59 MBq/g, E: >2.59 MBq/g. The therapeutic effect was evaluated by observing after treatment. And calculate the recovery rate, the improvement rate and the incidence rate of hypothyroidism. Results (①One hundred and fifty-two (64.95%) patients were cured, 56 (23.93%) were much better than before and 26 (11.11%) were hypothyroid. The therapeutic effect of group B was the best in all groups. ②The recovery rate: there was no significant difference between group B, group C and group D(χ2 =2.68, P>0.05 ). The recovery rate of group B was better than group A and group E (χ2 = 10.20 and χ2 =5.49,P<0.05 ). The recovery rate of group A was the lowest. ③The improvement rate: There was no significant difference between group B, group C, group D and group E(χ2 =1.94, P>0.05 ). The improvement rate of group A was the highest(χ2 =8.74,χ2 =6.68,χ2 =7.01 and χ2 =11.12, P<0.05 ). ④The incidence rate of hypothyroidism: There was no significant difference between group A, group B, group C and group D (χ2 =2.71, P>0.05 ). Group E had the highest incidence rate of hypothyroidism(χ2 =12.36, χ2 =11.58,χ2=9.37 and χ2=4.36, P<0.05 ). Conclusions Using 131I is a safe and effective therapeutic approach for youngsters with Graves disease. We suggest the absorbed dose range of 131I per gram of thyroid gland is 1.48-2.59 MBq/g,which can obtain the better therapeutic effect and can't increase the incidence rate of hypothyroidism.

  13. Prenatal radiation doses from radiopharmaceuticals

    International Nuclear Information System (INIS)

    The radiopharmaceutical administration with diagnostic or therapeutic purpose during pregnancy implies a prenatal radiation dose. The dose assessment and the evaluation of the radiological risks become relevant due to the great radiosensitivity of the fetal tissues in development. This paper is a revision of the available data for estimating fetal doses in the cases of the more frequently used radiopharmaceuticals in nuclear medicine, taking into account recent investigation in placental crossover. The more frequent diagnostic and therapeutic procedures were analyzed according to the radiation doses implied. (author)

  14. Therapeutic Effect Observation on Intravenous Low-dose Erythromycin Administration for Very Low Birth Weight Infants with Feeding Intolerance%小剂量红霉素治疗极低出生体重儿喂养不耐受疗效观察

    Institute of Scientific and Technical Information of China (English)

    尹武旋; 熊颖; 刘成军

    2011-01-01

    目的:观察小剂量红霉素对极低出生体重儿喂养不耐受的治疗效果.方法:将52例极低出生体重儿随机分为治疗组和对照组各26例.治疗组用小剂量红霉素静脉滴注,疗程7 d,对照组采用体位疗法.结果:治疗组总有效率为92.30%,对照组总有效率为 61.53%,二者比较差异有统计学意义(P<0.01).结论:小剂量红霉素静脉滴注治疗极低出生体重儿喂养不耐受效果好,且药价便宜,使用方便,值得临床推广应用.%Objective: To study the therapeutic effect of intravenous low-dose erythromycin administration fro very low birth weight infants (VLBWI) with feeding intolerance. Methods: Fifty-two VLBWI were divided into therapeutic and control groups with 26 cases in each group. The therapeutic group was given intravenous low-dose erythromycin administrations for 7 days, while the control group patients were given position treatment. Results: The total effective rate in the therapeutic group was significantly higher than that in the control group (92.30% , 61.53% , respectively, P < 0.01 ). Conclusions: Therapeutic effect of intravenous low-dose erythromnycinadministration for VLBWI with feeding intolerance is good, which is worthy of clinical promotion.

  15. Neuroprotective effect of high-dose hyperbaric oxygenation on rats with acute cerebral infarction in super-early stage Curative comparison between 9-hour and 18-hour therapeutic protocols

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Previously, only single short-time low-dose hyperbaric oxygenation (HBO) protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few studies to report the outcome of administering long-time (can cover all the natural pathologic progression period) high-dose HBO to treat the disease.OBJECTIVE: To evaluate the therapeutic effect between two kinds of high-dose hyperbaric oxygenation on super-early stage of acute permanent middle cerebral artery occlusion (MCAO) in rats.DESIGN: A randomized controlled experimental study.SETTING: Beijing Tiantan Hospital, Capital Medical University; Beijing Research Institute of Neurosurgery.MATERIALS: Seventy-four male SD rats, aged 2.5 months old, weighing (280±20) g, were provided by the Animal Institute, Chinese Academy of Medical Sciences. Hyperbaric oxygenation device was hyperbaric air cabin in which there was a self-made pure oxygen animal experimental cabin (made in China).METHODS: This experiment was carried out in the municipal laboratory of Beijing Tiantan Hospital affiliated to Capital Medical University and Beijing Research Institute of Neurosurgery. ① Experimental intervention: All the rats were developed into models of permanent MCAO by suture embolism. Then, they were randomly divided into two HBO groups (9hours and 18 hours) and control group, with 24 rats in each as well as 3-hour ultrastructure control group, with 2 rats. After being modeled for 3 hours, rats in the two HBO groups stayed in the hyperbaric cabin for 9 hours and 18 hours,separately. Rats in the 9-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7 and 9, and hyperbaric air at hours 2, 4, 6 and 8. Rats in the 18-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7, 9, 11, 13, 15 and 17, and hyperbaric air at hours 2, 4, 6, 8, 10 12, 14, 16 and 18. After being created into models, rats in the control group and 3-hour ultrastructure control group breathed room air.

  16. Therapeutic ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Crum, Lawrence A [Center for Industrial and Medical Ultrasound, 1013 NE 40th Street, University of Washington, Seattle, WA 98105 (United States)

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  17. Therapeutic alliance.

    Science.gov (United States)

    Fox, Valerie

    2002-01-01

    I have been very fortunate in my journey of mental illness. I respond well to medication, but I don't think that is the complete answer to living successfully with serious, persistent mental illness. I believe a person's environment is also of utmost importance, enabling the person suffering with mental illness to continually grow in life. I found early in my struggle with mental illness a psychiatrist with whom I have always had a very good rapport. Until recently I didn't know that what I have with this psychiatrist is professionally known as a therapeutic alliance. Over the years, when I need someone to talk over anything that is troubling to me, I seek my psychiatrist. A therapeutic alliance is non-judgmental; it is nourishing; and finally it is a relationship of complete trust. Perhaps persons reading this article who have never experienced this alliance will seek it. I believe it can make an insecure person secure; a frightened person less frightened; and allow a person to continue the journey of mental health with a sense of belief in oneself. PMID:12433224

  18. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  19. Diagnostic and therapeutic radiation exposure

    International Nuclear Information System (INIS)

    Diagnostic and therapeutic radiology were studied as possible contaminants in the evaluations of A-bomb survivors in the ABCC-JNIH Adult Health Study for radiation effects. Hiroshima and Nagasaki subjects received X-ray examinations elsewhere within three months of their ABCC visits at rates of 23 and 12%, respectively. Medical X-ray examinations were more frequent among survivors than comparison subjects. Hiroshima and Nagasaki radiologic practice steadily increased since 1948, and differed markedly by city. From 1946-70 the Hiroshima and Nagasaki X-ray bone marrow doses were 2,300 and 1,000 g-rads, respectively. By 1970, cumulated medical X-ray doses approximated A-bomb doses at distances from the hypocenters of 2,000 m in Hiroshima and 2,800 m in Nagasaki. ABCC X-ray examination doses per subject are routinely updated for comparison with A-bomb doses. Each subject's reported fluoroscopy, photofluorography and radiation therapy exposure elsewhere are for future reference. Dental radiography, though increasing, was not currently an important contributor to survivors' overall exposure. Radiation therapy exposures of 137 subjects were confirmed, and doses estimated for most. Two-thirds the treatments were for malignancies; therapy differed markedly by city; and five cancers possibly arose from earlier radiation therapy. This underscores the importance of considering diagnostic and therapeutic radiology when attributing diseases to the atomic bombs. (auth.)

  20. Depletion of eugenol residues from the skin-on fillet tissue of rainbow trout exposed to 14C-labeled eugenol

    Science.gov (United States)

    Meinertz, Jeffery R.; Schreier, Theresa M.; Porcher, Scott T.; Smerud, Justin R.; Gaikowski, Mark P.

    2014-01-01

    The U.S. is lagging in access to an approved immediate-release sedative, i.e. a compound that can be safely and effectively used to sedate fish and has no withdrawal period. AQUI-S® 20E (10% active ingredient, eugenol) is under investigation as an immediate-release sedative for freshwater finfish. Because of its investigational status, data are needed to characterize the depletion, distribution, and identity of AQUI-S® 20E residues in fillet tissue. Rainbow trout (Oncorhynchus mykiss) were exposed to uniformly ring labeled 14C-eugenol at a nominal concentration of 10 mg/L for 60 min in 18 °C water. Fish (n = 6) were sampled immediately after the exposure (0 min) then at 30, 60, 120, and 240 min. Eugenol concentrations and characterization of 14C residues in the fillet tissue were determined by high pressure liquid chromatography and flow-through liquid scintillation counting techniques. Total 14C-residue burdens in fillet tissue were determined by tissue oxidation and static liquid scintillation counting techniques. Maximum eugenol and 14C-eugenol equivalent residue concentrations in the fillet tissue were measured immediately after the exposure (44.5 and 38.8 μg/g, respectively). Eugenol was the primary 14C-residue (> 90% of all 14C-residues) in extracts from fillet tissue taken from fish sampled immediately after the exposure (0 min) and from fish sampled at 30 and 60 min after the exposure. The depletion of 14C-eugenol residues from the fillet tissue was rapid (t1/2 = 26.25 min) after transferring the exposed fish to fresh flowing water.

  1. Binding of /sup 14/C-labeled food mutagens (IQ, MeIQ, MeIQx) by dietary fiber in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Sjoedin, P.B.; Nyman, M.E.; Nilsson, L.; Asp, N.L.; Jaegerstad, M.

    Binding of three mutagens, known to occur in fried or broiled foods, by thirteen different types of dietary fiber was investigated in vitro. Nonspecific binding by other food polymers was minimized by using protease and amylase treatment. Water-insoluble fiber components were responsible for most of the binding capacity. Generally, a slightly larger proportion of 2-amino-3,4-dimethylimidazo (4,5-f)quinoline (MeIQ) than of 2-amino-3-methylimidazo (4,5-f)quinoline (IQ) and 2-amino-3,8-dimethylimidazo) -4,5-f)quinoxaline (MeIQx) was bound. There was a significant correlation between Klason lignin content and binding of mutagens. Optimum pH for binding was between 4 and 6. Dietary fiber from sorghum had the highest binding capacity, which could be due to the presence of a large Klason lignin fraction.

  2. Facile synthesis of deuterated and [14C]labeled analogues of vanillin and curcumin for use as mechanistic and analytical tools

    OpenAIRE

    Gordon, Odaine N.; Graham, Leigh A.; Schneider, Claus

    2013-01-01

    Curcumin is a dietary diphenol with antioxidant, antinflammatory and antitumor activity. We describe facile procedures for the synthesis of [14C2]curcumin (4 mCi/mmol), [d6]curcumin, [d3]curcumin, [13C5]curcumin, and [d6]bicyclopentadione, the major oxidative metabolite of curcumin. We also describe synthesis of the labeled building blocks [14C]vanillin, [d3]vanillin, and [13C5]acetylacetone. The overall molar yields of the labeled products were 52% ([14C]) and 47% ([d3]) for vanillin and 25%...

  3. Metabolism of 3H- and 14C-labeled glutamate, proline, and alanine in normal and adrenalectomized rats using different sites of tracer administration and sampling.

    Science.gov (United States)

    Said, H M; Chenoweth, M; Dunn, A

    1989-08-01

    Alanine, glutamate and proline labeled with 14C and 3H were infused into fasted normal and adrenalectomized rats. Alanine was administered by the A-V mode (arterial administration-venous sampling), and glutamate and proline by both the A-V and V-A (venous administration-arterial sampling) modes. The kinetics of 14C alanine and 14C glutamate differed markedly from those of the tritium-labeled compounds, but there was little difference in the kinetics of 3H and 14C proline. The replacement rate calculated from the A-V mode for glutamate was about half that obtained in the V-A mode, but there was little difference with proline. The masses of the amino acids (total content of amino acids in the body) were calculated from the washout curves of the tritium-labeled compounds after the infusion of tracer was terminated. The masses for the normal rats were 407 mumol/kg for alanine, 578 mumol/kg for glutamate and 296 mumol/kg for proline. The so-called distribution spaces calculated conventionally from total masses and the amino acid concentrations in plasma are much greater than the volume of the body, reflecting the fact that amino acid concentrations in tissues greatly exceed those in plasma. Adrenalectomy markedly affected the kinetics of the three amino acids, and their replacement rates were greatly reduced. The proline and glutamate masses were reduced by at least one half, while that of alanine was unchanged. Adrenalectomy markedly reduced the conversion of proline to glutamate. The hydrocortisone regimen used in this study restored the metabolism of alanine and glutamate to normal, but had no effect on that of proline. PMID:2569659

  4. Synthesis of [14C]-labelled dihydropyridine calcium channel entry blockers: nicardipine-[4[14C] and RS-93522-[4-14C

    International Nuclear Information System (INIS)

    The Hantzsch synthesis has been applied to the general preparation of 4-aryl-dihydropyridines labelled in the metabolically stable 4-position of the dihydropyridine ring. The synthesis is based on the preparation of a key common intermediate, m-nitrobenzaldehyde-[formyl-14C], in high yield from Ba14CO3. (author)

  5. Shake-flask test for determination of biodegradation rates of 14C-labelled chemicals at low concentrations in surface water systems

    DEFF Research Database (Denmark)

    Ingerslev, F.; Nyholm, Niels

    2000-01-01

    experience with the method is presented for a set of reference substances. These substances could be ranked in five groups of decreasing biodegradability: aniline > p-nitrophenol, 2,4-dichlorophenoxyacetic acid > 4-chloroaniline > maleic hydrazide, pentachlorophenol > atrazine, It was found that degradation...

  6. Comparison of the efficacy of biodegradable and non-biodegradable scintillation liquids on the counting of tritium- and [14C]-labeled compounds

    Directory of Open Access Journals (Sweden)

    Medeiros R.B.

    2003-01-01

    Full Text Available The widespread use of ³H and 14C in research has generated a large volume of waste mixed with scintillation liquid, requiring an effective control and appropriate storage of liquid radioactive waste. In the present study, we compared the efficacy of three commercially available scintillation liquids, Optiphase HiSafe 3, Ultima-Gold(TM AB (biodegradable and Insta-Gel-XF (non-biodegradable, in terms of [14C]-glucose and [³H]-thymidine counting efficiency. We also analyzed the effect of the relative amount of water (1.6 to 50%, radioisotope concentration (0.1 to 100 nCi/ml, pH (2 to 10 and color of the solutions (samples containing 0.1 to 1.0 mg/ml of Trypan blue on the counting efficiency in the presence of these scintillation liquids. There were few significant differences in the efficiency of 14C and ³H counting obtained with biodegradable or non-biodegradable scintillation liquids. However, there was an 83 and 94% reduction in the efficiency of 14C and ³H counting, respectively, in samples colored with 1 mg/ml Trypan blue, but not with 0.1 mg/ml, independent of the scintillation liquid used. Considering the low cost of biodegradable scintillation cocktails and their efficacy, these results show that traditional hazardous scintillation fluids may be replaced with the new safe biodegradable fluids without impairment of ³H and 14C counting efficiency. The use of biodegradable scintillation cocktails minimizes both human and environmental exposure to hazardous solvents. In addition, some biodegradable scintillation liquids can be 40% less expensive than the traditional hazardous cocktails.

  7. Effects of the invasive polychaete, Marenzelleria viridis, on the fate of sediment associated pollutants – a microcosm study with 14C-labelled pyrene

    DEFF Research Database (Denmark)

    Banta, Gary Thomas; Hedman, Jenny Elisabet

    The deep burrowing, invasive spionid polychaete, Marenzelleria spp. (3 sibling species), is rapidly expanding its range in the Baltic Sea ecosystem, increasing the depth of the bioturbated zone dramatically relative to the native benthic community. One concern is the effect of this invasion...

  8. Experiments for a systematic comparison between stable-isotope-(deuterium) labeling and radio-((14)C) labeling for the elucidation of the in vitro metabolic pattern of pharmaceutical drugs.

    Science.gov (United States)

    Grunwald, Helge; Hargreaves, Patrick; Gebhardt, Klaus; Klauer, Dominique; Serafyn, Arnaud; Schmitt-Hoffmann, Anne; Schleimer, Michael; Schlotterbeck, Goetz; Wind, Mathias

    2013-11-01

    A systematic comparison between two labeling approaches for the investigation of the in vitro metabolic pattern of pharmaceutical drugs was performed by examining the use of (i) radiolabeled drugs analyzed with LC-MS-offline radiodetection and (ii) stable-isotope labeled drugs, used in a defined mixture with the unlabeled drug and analyzed by LC-MS with recognition of the specific isotopic pattern. (14)C was used for the radioisotope-approach and deuterium for the stable-isotope approach. Olanzapine, diclofenac and ketoconazole were chosen as model drugs, as they are commercially available in their non-, radio- and stable-isotope labeled forms. For all three model drugs, liver microsome- and hepatocyte-incubations (both from rat) were performed with various concentrations and incubation times for both, the radio- and the stable-isotope approaches. The metabolic pattern, including structure elucidation of all detected metabolites, was performed independently for all individual compounds and incubations. Subsequently, the metabolic patterns of the radio-, and the stable-isotope approaches were compared. In conclusion, all metabolites found with the radioisotope approach could also be found with the stable-isotope approach. Although the stable-isotope approach does not provide a quantitative result, it can be considered to be a highly suited analytical alternative for early in vitro metabolism investigations, especially when radiolabeled drug analogues are not yet available and quantitative results are not yet necessary. PMID:23933567

  9. The turnover of 14C labelled groundnut straw, soil organic matter dynamics, and CO2 evolution in an Alfisol and a Vertisol of semi-arid tropical India

    International Nuclear Information System (INIS)

    During all seasons and experiments in a prevailing warm climate in the Indian semi-arid tropics, the turnover of uniformly 14C tagged groundnut straw was faster in the shallow, sandy Alfisol than in the deep clayey, smectitic Vertisol. In both soils, the initial 14C losses were highest in the first weeks when straw was incorporated in the rainy season. After 2.5 years, the residual 14C accounted for 14% in the Alfisol and for 26% in the Vertisol. The straw burial in the hot dry season resulted in considerable losses in desiccated soils what agreed to studies under controlled environmental conditions. Following frequent dry/wet cycles in the field, further drastic decline of straw-derived 14C was observed. Also, 14C losses were more pronounced in the drier postrainy season than in the rainy seasons underlining the effective adaptation of soil microbes to moisture conditions far below field capacity. Labelled groundnut roots decomposed much slower than aboveground biomass during half a year in the rainy season. In all field experiments, shading favored larger turnover of 14C. That was attributed to prolonged soil moisture under shade where the positive effects of higher temperature on more rapid litter decay in the open were offset. Recordings of CO2 during 2 years showed no impacts of living roots on retardation of 14CO2-C fluxes if compared to release rates from fallow/bare treatments. (orig./EF)

  10. Experimental soil warming and cooling alters the partitioning of recent assimilates: evidence from a (14)C-labelling study at the alpine treeline.

    Science.gov (United States)

    Ferrari, A; Hagedorn, F; Niklaus, P A

    2016-05-01

    Despite concerns about climate change effects on ecosystems functioning, little is known on how plant assimilate partitioning changes with temperature. Particularly, large temperature effects might occur in cold ecosystems where critical processes are at their temperature limit. In this study, we tested temperature effects on carbon (C) assimilate partitioning in a field experiment at the alpine treeline. We warmed and cooled soils of microcosms planted with Pinus mugo or Leucanthemopsis alpina, achieving daily mean soil temperatures (3-10 cm depth) around 5.8, 12.7 and 19.2 °C in cooled, control and warmed soils. We pulse-labelled these systems with (14)CO2 for one photoperiod and traced (14)C over the successive 4 days. Plant net (14)C uptake increased steadily with soil temperature. However, (14)C amounts in fungal hyphae, soil microbial biomass, soil organic matter, and soil respiration showed a non-linear response to temperature. This non-linear pattern was particularly pronounced in P. mugo, with five times higher (14)C activities in cooled compared to control soils, but no difference between warmed and control soil. Autoradiographic analysis of the spatial distribution of (14)C in soils indicated that temperature effects on the vertical label distribution within soils depended on plant species. Our results show that plant growth, in particular root metabolism, is limited by low soil temperature. As a consequence, positive temperature effects on net C uptake may not be paralleled by similar changes in rhizodeposition. This has important implications for predictions of soil C storage, because rhizodeposits and plant biomass vary strongly in their residence times. PMID:26314342

  11. Evaluation of 14C labelled solvents for its use in the E.R.A. technique in the case of curing of unsaturated poliesters

    International Nuclear Information System (INIS)

    The Evaporative Rate Analysis (E.R.A.) technique was evaluated for the study of the curing of unsaturated polyesters as a function of time. Ethylene glycol monoethyl ether acetate 14C was found to be a suitable solvent for this purpose. Determinations take less than 5 minutes, thus avoiding the problems of long test-time which often introduces uncertainly about the real curing time of the sample. (author)

  12. [Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

    Science.gov (United States)

    Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

    2012-01-01

    The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug. PMID:23196511

  13. Effect observation and mechanism of low - dose decitabine combined with modified CAG therapeutic regimen in the treatment of patients with myelodysplastic syndrome(MDS)%低剂量地西他滨序贯改良 CAG 方案对治疗骨髓增生异常综合征的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    陈喜填; 夏维林; 林东; 王楚林; 张淳嘉; 吴桂香

    2016-01-01

    目的:探究低剂量地西他滨序贯改良 CAG 方案对治疗中高危骨髓增生异常综合征(Myelodysplastic syn-drome,MDS)的临床疗效。方法:随机抽取收治的中高危 MDS 患者96例,分为观察组46例及对照组患者50例,其中观察组患者采用低剂量地西他滨序贯 CAG 方案进行治疗,而对照组患者均采用 CAG 方案进行治疗,观察两组患者的临床疗效、不良反应的发生情况及处理结果。结果:观察组比对照组患者的疾病缓解率更高、疗效更显著,且两组比较差异具有统计学意义(P ﹤0.05)。结论:低剂量地西他滨序贯改良 CAG 方案治疗高危 MDS 比单用 CAG 方案疗效更明显、确切。%Objective The objection of the study was to investigate the clinical efficiencies and adverse reactions of treating the myelodysplastic syndrome(MDS)by using low - does decitabine combined with modified CAG therapeutic regimen. Method 96 high - risk MDS patients were randomly selected,they were divided into observation group with 46 cases and control group with 50 cases. The observation group was treated with low - dose decitabine combined with modified CAG therapeutic regimen, while the control group was treated with CAG therapeutic regimen. Clinical efficacy,adverse reactions and treatment results of each group were observed and analyzed. Results The remission rate was higher and the curative effect was more significant of ob-servation group when compared with control group,the difference between two groups has statistical significance( P ﹤ 0. 05) . Conclusion The effect of high risk MDS in treatment with low dose of decitabine combined with modified CAG therapeutic regi-ment is more significance than treated with CAG therapeutic regimen.

  14. Therapeutical uses of 131I

    International Nuclear Information System (INIS)

    Physiology of thyroid gland, pathology of thyroid , papillary, follicular cancer is considered together as differentiated thyroid cancer with very good results under therapy with iodine, invitro determination of calcitonin, search of metastasis, anaplastic carcinoma, as indifferentiated carcinoma with similar results as medullary carcinoma. This work gives a protocol for therapeutical use of 131I , in hyperthyroidism due to Graves-Basedow disease, thyrotoxic adenoma or Plummer disease, toxic multi nodular goiter, subacute thyroiditis. Is studied too the treatment with pharmaceuticals, surgery and radioactive iodine. A recommended use of each and protocol for iodine administration, fixed dose technique, dose estimation,absorbed dose, recommendations about when to use and not use 131I are included in this work

  15. Dose limits

    International Nuclear Information System (INIS)

    The dose limit is defined to be the level of harmfulness which must not be exceeded, so that an activity can be exercised in a regular manner without running a risk unacceptable to man and the society. The paper examines the effects of radiation categorised into stochastic and non-stochastic. Dose limits for workers and the public are discussed

  16. Therapeutical aspect of trichomoniasis

    Directory of Open Access Journals (Sweden)

    Vukićević Jelica

    2003-01-01

    Full Text Available Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center [19]. The resistance of Trichomonas vaginalis (TV strains to metronidazole (MND was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001 612 patients (244 females and 368 males suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects. Trichomonas infection was found in 90 (36.88 % out of 244 tested females and in 126 (32.34 % of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases. The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05. The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three

  17. Utilización del citrato de fentanilo oral transmucosa como rescate terapéutico en pacientes con altas dosis de opioides Use of oral transmucosal fentanyl citrate for therapeutic rescue in patients receiving high doses of opiates

    Directory of Open Access Journals (Sweden)

    J. Cevas

    2005-07-01

    crisis de DI en pacientes oncológicos que tienen controlado su dolor basal con dosis altas de opioides. Las dosis de CFOT pueden considerarase como bajas en relación a las utilizadas para su dolor basal. Su administración y titulación es sencilla, aunque el paciente requiere de una educación previa a su uso.The management of breakthrough pain in cancer patients treated with high doses of opiates raises particular problems, such as the election of the drug to be used, the appropriate dosage and the route of administration. No clear guidelines on this issue are found in the medical literature, so each service decides its own particular way of acting. In this paper we review the cases dealt with over a one-year period in terms of the use of high doses of opiates in cancer patients taken care of in 2003 and treated with opiates. Objectives: -To study the group of patients treated with high doses of opiates. -To use OTFC as rescue drug for breakthrough pain events. -To analyze side and toxic effects. -To determine the preferences of the patients. Material and methods: A population of 280 patients with advanced cancer, 25 of which were receiving high doses of opiates. In these patients, breakthrough pain crises were managed with OTFC, starting with 400 micrograms. The satisfaction questionnaire proposed by Kornick was used. Results: -Easy adherence to treatment. -Average effective dose of OTFC: 600 micrograms, median of 627. -Dose titration on the second day. -Seventeen patients preferred OTFC, 6 preferred oral morphine and 2 were indifferent. Conclusions: Easy use of OTFC for the management of breakthrough pain, requiring low doses compared to the total daily dose of the patient. Patient education is required before its administration.

  18. Synergistic drug combinations improve therapeutic selectivity

    OpenAIRE

    Lehàr, Joseph; Krueger, Andrew S.; Avery, William; Heilbut, Adrian M; Johansen, Lisa M.; Price, E. Roydon; Rickles, Richard J.; Short, Glenn F; Staunton, Jane E.; jin, xiaowei; Lee, Margaret S.; Zimmermann, Grant R; Borisy, Alexis A.

    2009-01-01

    Prevailing drug discovery approaches focus on compounds with molecular selectivity, inhibiting disease-relevant targets over others in vitro. However in vivo, many such agents are not therapeutically selective, either because of undesirable activity at effective doses or because the biological system responds to compensate. In theory, drug combinations should permit increased control of such complex biology, but there is a common concern that therapeutic synergy will generally be mirrored by ...

  19. Study of Therapeutic Dose Change of Thyroid Hormones of Patients with Hypothyroidism during Pregnancy%甲状腺功能减退患者妊娠期间甲状腺激素治疗剂量的变化研究

    Institute of Scientific and Technical Information of China (English)

    张英霞

    2013-01-01

    目的:探讨妊娠期间甲状腺功能减退患者的甲状腺激素治疗剂量的调整规律。方法:选择于我院接受治疗的甲状腺功能减退的患者作为研究对象,将处于妊娠期间的患者作为实验组,非妊娠期间的患者作为对照组,收集两组患者的临床资料,比较两组患者甲状腺激素治疗的变化规律,并统计实验组患者在妊娠期间较妊娠期前后的甲状腺激素使用剂量变化百分比的变化。结果:实验组的患者在妊娠期间甲状腺激素的使用量显著高于对照组,其差异具有统计学意义(P<0.05);实验组患者妊娠期间甲状腺激素的使用量显著高于妊娠前及分娩后,差异具有差异。结论:甲状腺功能减退患者妊娠期间需加大甲状腺激素的治疗量,分娩后期所需量有所下降。%Objective: To discuss the regulation law of therapeutic dose change of thyroid hormones of patients with hypothyroidism during pregnancy. Method:Patients with hypothyroidism were chosen as study objects. Patients during pregnancy were marked as experiment group and patients not during pregnancy were marked as control group. Clinical data of the 2 groups were col ected. Change laws of thyroid hormones treatment of the 2 groups were compared. The percentage changes of therapeutic dose of thyroid hormones of patients with hypothyroidism during pregnancy to before and after pregnancy were counted. Result: Usage amount of thyroid hormone of experiment group during pregnancy was obviously bigger than control group and than before and after pregnancy (P<0.05). Conclusion: Patients with hypothyroidism during pregnancy should increase therapeutic dose of thyroid hormone and decrease after pregnancy.

  20. Controllable dose

    International Nuclear Information System (INIS)

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  1. [Therapeutic effects of larger doses of arachidonic acid added to DHA on social impairment and its relation to alterations of polyunsaturated fatty acids in individuals with autism spectrum disorders].

    Science.gov (United States)

    Yui, Kunio; Koshiba, Mamiko; Nakamura, Shun; Onishi, Masako

    2011-06-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA) and docosahexaenoic acid (DHA) may play key roles in brain network maturation. ARA plays an important role in signal transduction related to neuronal maturation. This study aims to evaluate the efficacy of supplementing with larger doses of ARA added to DHA in a double-blind, placebo-controlled 16-week trial. To confirm findings observed in the placebo-controlled trial, an additional 16-week open-label study was further conducted. To examine the relationship between the efficacy of the supplementation regimen and alterations in PUFAs levels, we examined plasma levels of PUFAs. We used the Social Responsiveness Scale (SRS) and the Aberrant Behavior Checklist-Community (ABC) to estimate psychotic symptoms. Repeated measures ANOVA revealed that this supplementation significantly improved SRS-measured communication as well as ABC-measured social withdrawal during the placebo-controlled trial. The treatment effect sizes were more favorable for the treatment group compared with the placebo group (communication: 0.87 vs. 0.44; social withdrawal: 0.88 vs. 0.54). At the end of the placebo-controlled trial, there was a significant difference in the change in plasma ARA levels from the baseline and a trend towards a significant difference in plasma ARA levels between the two groups. The open-label study was not powered to detect significant improvements in the outcome measures or significant differences in plasma ARA levels. The present clinical trials suggest that supplementation with larger ARA doses added to DHA improves social impairment in individuals with ASD via ARA-induced upregulation of neuronal functioning. PMID:21800702

  2. Therapeutic trial of intensified conditioning regimen with high-dose cytosine arabinoside, cyclophosphamide and either total body irradiation or busulfan followed by allogeneic bone marrow transplantation for myelodysplastic syndrome in children

    Energy Technology Data Exchange (ETDEWEB)

    Nagatoshi, Yoshihisa; Okamura, Jun; Ikuno, Yoshiko; Akamatsu, Minoru; Tasaka, Hideko [National Kyushu Cancer Center, Fukuoka (Japan)

    1997-04-01

    Ten children with myelodysplastic syndrome underwent an allogeneic bone marrow transplantation (BMT) with an intensified conditioning regimen. The median age of the patients was 8 years (range 2-10), and included 6 males and 4 females. The subtype of the disease was refractory anemia (RA) in 4, RA with excess blasts (RAEB) in 4, RAEB in transformation (RAEB-T) in 1, and juvenile chronic myelogenous leukemia (JCML) in 1. All patients were conditioned with high-dose cytosine arabinoside (12000 mg/m{sup 2}), cyclophosphamide (120 mg/kg) and either total body irradiation (10-13.2 Gy) or busulfan (16 mg/kg or 560 mg/m{sup 2}). Cyclosporine A and/or methotrexate were used for the prophylaxis of graft-versus-host disease (GVHD). Engraftment was prompt in all but one patient. Severe acute GVHD (grade 3) (n=1), interstitial pneumonitis (n=1) and veno-occlusive disease of the liver (n=1) occurred. The disease relapsed in one patient with RAEB-T. Seven of the 10 patients were alive and disease free 2-74 months after BMT. The disease-free survival rate at 4 years was 69{+-}15%. All surviving patients were in the full performance status. The examined children with MDS tolerated this intensified conditioning regimen well. (author)

  3. DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic

    Directory of Open Access Journals (Sweden)

    Roberts Jason A

    2012-07-01

    Full Text Available Abstract Background The clinical effects of varying pharmacokinetic exposures of antibiotics (antibacterials and antifungals on outcome in infected critically ill patients are poorly described. A large-scale multi-centre study (DALI Study is currently underway describing the clinical outcomes of patients achieving pre-defined antibiotic exposures. This report describes the protocol. Methods DALI will recruit over 500 patients administered a wide range of either beta-lactam or glycopeptide antibiotics or triazole or echinocandin antifungals in a pharmacokinetic point-prevalence study. It is anticipated that over 60 European intensive care units (ICUs will participate. The primary aim will be to determine whether contemporary antibiotic dosing for critically ill patients achieves plasma concentrations associated with maximal activity. Secondary aims will compare antibiotic pharmacokinetic exposures with patient outcome and will describe the population pharmacokinetics of the antibiotics included. Various subgroup analyses will be conducted to determine patient groups that may be at risk of very low or very high concentrations of antibiotics. Discussion The DALI study should inform clinicians of the potential clinical advantages of achieving certain antibiotic pharmacokinetic exposures in infected critically ill patients.

  4. 小剂量强力霉素联合甲硝唑凝胶治疗酒渣鼻疗效观察%The Therapeutic Effect of Small Doses Doxycycline Combine Metronidazole Gel for Rosacea

    Institute of Scientific and Technical Information of China (English)

    郝江华; 郗宁; 唐晓琳

    2012-01-01

    Objective To observe the clinical efficacy and safety of small doses doxycycline combined with topical metronidazole gel in the treatment of rosacea. Methods Ninety cases of rosacea were divided randomly into three groups,the treatment group(n=30) were given doxycycline 20mg orally plus 0.75% metronidazole gel topically twice a day. The control group 1 (n=30)only orally took doxycycline 20mg two times per day,and the control group 2 (n=30)only applied 0.75% metronidazole gel twice a day. All groups had been given four-week courses. Results Total efficiency in the treatment group was 96.55%, which was better than that of control group 1 (75.00%)and the control group 2(76.67%) (P 0.05). Mild local desiccation occured equally in both the treatment group and the control group 2, adverse reaction rate were 10.34% in the treatment group and 13.33% in the control group 2. Adverse reaction was not be founded in the control group 1. Conclusion The combination therapy of small doses of doxycycline and topical metronidazole gel is safe and effective in the treatment of rosacea.%目的 观察小剂量强力霉素联合甲硝唑凝胶治疗酒渣鼻的临床疗效和安全性.方法 将入选的90例酒渣鼻患者随机分成3组,各30例,治疗组口服强力霉素20mg,同时外搽0.75%甲硝唑凝胶,均2次/d;对照1组仅口服强力霉素,对照2组仅外用0.75%甲硝唑凝胶,用法同治疗组,均4周为1个疗程,共治疗3个疗程.每个疗程结束后分别观察疗效.结果 治疗组有效率(96.55%)明显优于对照1组(75.00%)和对照2组(76.67%),差异均有统计学意义(P均<0.05),而对照1组有效率和对照2组比较差异无统计学意义(P>0.05).治疗组不良反应发生率为10.34%、对照2组为13.33%,该两组均表现为用药局部皮肤轻度干燥,对照1组未见不良反应.结论 小剂量强力霉素联合甲硝唑凝胶外搽治疗酒渣鼻疗效肯定,安全性好.

  5. [Therapeutic drug monitoring of felbamate].

    Science.gov (United States)

    Tribut, Olivier; Bentué-Ferrer, Danièle; Verdier, Marie-Clémence

    2010-01-01

    Felbamate is a derivative of meprobamate used in second-line partial epilepsy and in the Lennox-Gastaut syndrome. Felbamate is well absorbed and has linear kinetics: C(max) and AUC increasing linearly with dose. The metabolism takes place in the liver. Metabolites represent 40 to 60% of excretion and are eliminated via the urine. The half-life is between 15 and 23 hours. Clearance is dependent on renal function. There is a concentration - efficacy and concentration - toxicity relationship. These arguments are in favour of a TDM but the therapeutic range is not clearly established. Potentially fatal side effects can be caused by felbamate (aplastic anemia, acute liver failure), which limits its use because they are dose-independant. PMID:20205993

  6. 大剂量rhG-CSF早期单次给药对60Coγ射线照射小鼠的治疗作用%Therapeutic effects of early administration of a single high dose of rhG-CSF on mice irradiated by 60Coγ rays

    Institute of Scientific and Technical Information of China (English)

    韩阿如娜; 余祖胤; 柳晓兰; 从玉文

    2011-01-01

    Objective To observe the therapeutic effects of early administration with a single high dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on mice irradiated with 60Co γ rays, and provide a reference for the treatment of acute radiation syndrome (ARS) by using cytokines. Methods Male C57 mice underwent a total body irradiation of 8. Ogy 60Co y ray, and they were treated with rhG-CSF, at 0.5h and 24h, subcutaneously in a dose of 2, 1 and 0. 5mg/kg, respectively. The 30-day survival rate and mean survival time were observed in the lethal irradiated mice. The peripheral blood cell counts and bone marrow nucleated cell counts were evaluated in the sublethally irradiated mice. Results Early administration of a high dose of rhG-CSF significantly increased 30-day survival rate and prolonged mean survival time of mice with lethal irradiation dose. A single injection of rhG-CSF (lmg/kg) at 0. 5h after irradiation was an optimal administration schedule. In addition, early administration with a single high dose of rhG-CSF improved the recovery of bone marrow nucleated cell counts and peripheral blood counts, including white blood cell (WBC), red blood cell (RBC) and platelet in mice exposed to 6. Ogy irradiation. Conclusion Early administration of a single high dose rhG-CSF may have a favorable therapeutic effect on mice irradiated with 60Co y ray.%目的 观察大剂量rhG-CSF早期单次给药对60Coγ射线照射小鼠的治疗作用,为细胞因子治疗急性放射病提供实验依据.方法 雄性C57小鼠,经8.0Gy 60Co γ射线全身照射后于0.5、24h各皮下注射一次不同剂量rhG-CSF(2、1mg/kg和0.5mg/kg),观察致死剂量照射小鼠的30d存活率及平均生存时间.小鼠经6.0Gy 60Co γ射线全身照射后,通过不同给药方案及不同剂量rhG-CSF早期干预,观察亚致死剂量照射小鼠的外周血象和骨髓有核细胞数的变化.结果 大剂量rhG-CSF早期干预明显提高致死剂量照射小鼠的30d存

  7. Dose and dose rate monitor

    International Nuclear Information System (INIS)

    The methods are discussea of measuring dose rate or dose using a scintillation counte. A plastic scintillator based on polystyrene with PBD and POPOP activators and coated with ZnS(Ag) was chosen for the projected monitor. The scintillators were cylindrical and spherical in shape and of different sizes; black polypropylene tubes were chosen as the best case for the probs. For the counter with different plastic scintillators, the statistical error 2σ for natural background was determined. For determining the suitable thickness of the ZnS(Ag) layer the energy dependence of the counter was measured. Radioisotopes 137Cs, 241Am and 109Cd were chosen as radiation sources. The best suited ZnS(Ag) thickness was found to be 0.5 μm. Experiments were carried out to determine the directional dependence of the detector response and the signal to noise ratio. The temperature dependence of the detector response and its compensation were studied, as were the time stability and fatigue manifestations of the photomultiplier. The design of a laboratory prototype of a dose rate and dose monitor is described. Block diagrams are given of the various functional parts of the instrument. The designed instrument is easiiy portable, battery powered, measures dose rates from natural background in the range of five orders, i.e., 10-2 to 103 nGy/s, and allows to determine a dose of up to 10 mGy. Accouracy of measurement in the energy range of 50 keV to 1 MeV is better than +-20%. (E.S.)

  8. 治疗剂量下4种抗结核药物与Caco-2细胞上P-gp相互作用研究%Initial Study on Interaction between Therapeutic Doses of Four Anti-Tuberculosis Drugs and P-Glycoprotein in Caco-2 Cells

    Institute of Scientific and Technical Information of China (English)

    方平飞; 高维; 李焕德; 刘艺平

    2011-01-01

    therapeutic doses of isoniazid and ethambutol decreased the accumulation of rhodamine123 in Caco-2 cells significantly compared with that of negative control group ( P < 0. 05). The therapeutic doses of isoniazid and ethambutol both up-regulated the cellular P-glycoprotein protein and MDR1 mRNA expression levels ( P <0. 05 ). Compared with the controls, the total quantity of P-glycoprotein were 3. 5 and 3.8 folds higher than that of controls, and the total levels of MDR1 mRNA expression were 11.5 and 11 folds higher than that of controls, respectively. Therapeutic doses of levofloxacin increased the accumulation of rhodamine123 in Caco-2 cells significantly higher than that of negative control group ( P < 0. 05 ). The therapeutic doses of levofloxacin down-regulated the cellular P-glycoprotein protein and MDR1 mRNA expression levels (P <0. 05 ). Compared with the controls, the total levels of P-glycoprotein and MDR1 mRNA expression were 50% and 32% of controls, respectively. Pyrazinamide showed no significant interaction with P-glycoprotein. CONCLUSION Therapeutic doses of isoniazid and ethambutol might be inducer of P-glycoprotein, levofloxacin might be inhibitors of pglycoprotein, and pyrazinamide showed no significant interaction with P-glycoprotein.

  9. The therapeutic effect of small dose of estrogen on cerebral infarction%小剂量雌激素对缺血性脑卒中的治疗作用

    Institute of Scientific and Technical Information of China (English)

    王明刚; 李春盛; 高春锦; 王硕; 段春苗

    2008-01-01

    (TC),triglyceride (TG),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C),IL-1β,NO,and NIHSS score were measured in each patient at time points of 0,3,7,14 and 21 days.Results In E2 group,HDL-C and Ez were increased significantly,and TC and LDL-C were decreased significantly from 3 days on after treatment,and the changes were obviously more marked than that of routine therapy group (all P<0.05).The changes in TG and Ts were not obvious.NO,IL-1β were increased significantly (both P<0.05),and NIHSS score was decreased in routine group form 14 days on after treatment.NO and IL-1β in E2 group were lower than those in routine therapy group from 3 days on,and the NIHSS score was significantly lower on 14 days and 21 days in E2 group (both P<0.05).Conclusion The protective effect of E2 is obvious.It may be due to the results of modulation of blood fat,anti-inflammation and modulation of NO production by the action of E2.Low dose and short time therapy of E2 may be beneficial to the patient.

  10. Predictive performance of gentamicin dosing nomograms

    Directory of Open Access Journals (Sweden)

    Lee J

    2014-08-01

    Full Text Available Jieon Lee,1 Seonghae Yoon,1 Donghoon Shin,1 HyeKyung Han,1 Hyungmi An,1,2 Jongtae Lee,1 Kyoung Soo Lim,3 Kyung-Sang Yu,1 Howard Lee11Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea; 2Department of Statistics, College of Natural Sciences, Seoul National University, Seoul, Korea; 3Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, KoreaBackground: Several nomograms have been proposed to facilitate the determination of initial gentamicin dosing regimens in clinical settings. This study aimed to assess the predictive performance of these nomograms in Korean patients.Methods: Gentamicin concentrations were determined in 84 patients with infective endocarditis (IE and in 95 patients with other infections. All patients underwent therapeutic drug monitoring in Seoul National University Hospital from 2006 to 2012. Individual pharmacokinetic parameters were estimated using a Bayesian method, which predicted steady state peak and trough serum concentrations. Six nomograms were evaluated in patients with "other" infections: the Thomson guidelines, Hull-Sarubbi table, and Rule of Eights, for multiple daily dosing; and the Hartford nomogram, Barnes-Jewish Hospital nomogram, and Sanford Guide, for extended-interval dosing. In IE patients, synergistic combination dosing nomograms, based on the American Heart Association dosing interval guidelines, were evaluated.Results: Gentamicin dosing nomograms performed poorly in attaining the target peak serum concentrations. Multiple-daily dosing nomograms predicted peak serum gentamicin concentrations better than did the extended-interval dosing nomograms (31.9%–72.3% vs 4.3%–45.7%, respectively. Similarly, in patients with IE, the once-daily dosing nomogram resulted in a significantly lower percentage of patients achieving target peak gentamicin concentrations

  11. Utilização da fenilefrina para controle da pressão arterial em cesarianas eletivas: dose terapêutica versus profilática Utilización de la fenilefrina para el control de la presión arterial en cesáreas electivas: dosis terapéutica versus profiláctica Phenylephrine for blood pressure control in elective cesarean section: therapeutic versus prophylactic doses

    Directory of Open Access Journals (Sweden)

    José Francisco Nunes Pereira das Neves

    2010-08-01

    administración de fenilefrina. En el Grupo 1, se administró fenilefrina en infusión continua, con bomba de infusión en dosis de 0,15 µg.Kg-1.min-1 después de la raquianestesia. En el Grupo 2, fue administrada fenilefrina en dosis única, de forma profiláctica, en dosis de 50 µg después de la raquianestesia, y en el Grupo 3, fenilefrina en dosis única de 50 µg en el caso de hipotensión arterial definida como una caída de la PAS y/o PAD en hasta un 20% con relación al promedio de los valores basales. Se evaluó la incidencia de hipotensión arterial, náuseas, vómitos y el índice de Apgar. RESULTADOS: La incidencia de hipotensión arterial fue significativamente más elevada en el Grupo 3, acaeciendo en un 85% de las embarazadas. En los Grupos 1 y 2, ocurrió en un 17,5% y 32,5% de los casos respectivamente (p BACKGROUND AND OBJECTIVES: Spinal block is commonly used in cesarean sections and, if some prophylactic measures are not taken, the incidence of hypotension is higher than 80%. The objective of this study was to compare the efficacy of the administration of therapeutic or prophylactic doses of phenylephrine to maintain blood pressure in patients undergoing spinal block for elective cesarean section. METHODS: One hundred and twenty gravidas undergoing elective cesarean sections under spinal block, randomly divided in three equal groups according to the regimen of phenylephrine administered, were included in this study. In Group 1, continuous infusion of phenylephrine, using an infusion pump at 0.15 µg.kg-1.min-1 was administered after the spinal block. In Group 2, a single dose of prophylactic phenylephrine 50 µg was administered after the spinal block, and Group 3 received a single dose of phenylephrine 50 µg in case of hypotension, which was defined as a drop in SBP and/or DBP of up to 20% of baseline levels. The incidence of hypotension, nausea, and vomiting as well as the Apgar score were evaluated. RESULTS: The incidence of hypotension was

  12. Therapeutic effects of sofalcone on experimental gastritis.

    Science.gov (United States)

    Kishimoto, S; Okamoto, K; Kambara, A; Kajiyama, G; Miyoshi, A; Suwa, T

    1987-08-01

    A study was made on the therapeutic effects of sofalcone (SU-88), an antiulcer agent, on erosive and atrophic gastritis induced experimentally by 6-month administration of 5 mmol/l of sodium taurocholate (TCA) in rats. A standard meal including sofalcone of 0.25% and 1.0% shortened the total length of erosions, normalized the mucosal thickness, and reduced collagenous fibers in the gastric mucosa in one month. The doses administered were 116.3 mg and 486.1 mg/kg/week for one month. Sofalcone, thus, had a good therapeutic effect on experimental erosive and atrophic gastritis in rats. PMID:3675690

  13. 小剂量肝素治疗急性白血病前DIC的疗效及安全性%The Therapeutic Effect and Safety of Low-Dose Heparin Therapy for Acute Leukemia with Pre-diffuse Intravascular Coagulation

    Institute of Scientific and Technical Information of China (English)

    王栋范

    2014-01-01

    Objective To analysis the therapeutic effect and safety of Low-Dose heparin therapy for acute leukemia with pre-diffuse intravascular coagulation. Method 48 cases randomly divided into 2 groups. The control group(n=24) took conventional treatment. The observation group (n=24)took conventional treatment accompany with low-dose heparin subcutaneous. Clinical indicators and adverse reaction were contrasted between the two groups. Result After treatment, there has significant different in platelet count, fibrinogen level and D-dimer level between the two groups (P<0.05). Rate of developing into DIC were lower in the observation group than that in the control group (P<0.05). None severe bleeding tendency exist. Conclusion Low-dose heparin therapy can effectively interrupt pre-DIC development to DIC.%目的:分析小剂量肝素治疗急性白血病前弥漫性血管内凝血(pre-DIC)的效果及安全性。方法48例患者随机分为2组,对照组(n=24)采用常规治疗,观察组(n=24)常规治疗加小剂量肝素皮下注射,对比两组临床指标及不良反应。结果观察组治疗后血小板计数、凝血酶原时间(PT)、D-二聚体含量均与对照组有显著性差异(P<0.05);观察组转化为DIC比例显著低于对照组(P<0.05);两组均未出现严重的出血症状。结论小剂量肝素治疗能够有效阻止急性白血病前弥漫性血管内凝血向DIC发展。

  14. Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock

    OpenAIRE

    Estevão Bassi; Marcelo Park; Luciano Cesar Pontes Azevedo

    2013-01-01

    There is no consensual definition of refractory shock. The use of more than 0.5 mcg/kg/min of norepinephrine or epinephrine to maintain target blood pressure is often used in clinical trials as a threshold. Nearly 6% of critically ill patients will develop refractory shock, which accounts for 18% of deaths in intensive care unit. Mortality rates are usually greater than 50%. The assessment of fluid responsiveness and cardiac function can help to guide therapy, and inotropes may be used if hyp...

  15. Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock

    Directory of Open Access Journals (Sweden)

    Estevão Bassi

    2013-01-01

    Full Text Available There is no consensual definition of refractory shock. The use of more than 0.5 mcg/kg/min of norepinephrine or epinephrine to maintain target blood pressure is often used in clinical trials as a threshold. Nearly 6% of critically ill patients will develop refractory shock, which accounts for 18% of deaths in intensive care unit. Mortality rates are usually greater than 50%. The assessment of fluid responsiveness and cardiac function can help to guide therapy, and inotropes may be used if hypoperfusion signs persist after initial resuscitation. Arginine vasopressin is frequently used in refractory shock, although definite evidence to support this practice is still missing. Its associations with corticosteroids improved outcome in observational studies and are therefore promising alternatives. Other rescue therapies such as terlipressin, methylene blue, and high-volume isovolemic hemofiltration await more evidence before use in routine practice.

  16. Therapeutic Recreation Practicum Manual.

    Science.gov (United States)

    Schneegas, Kay

    This manual provides information on the practicum program offered by Moraine Valley Community College (MVCC) for students in its therapeutic recreation program. Sections I and II outline the rationale and goals for providing practical, on-the-job work experiences for therapeutic recreation students. Section III specifies MVCC's responsibilities…

  17. Therapeutic postprostatectomy irradiation.

    Science.gov (United States)

    Youssef, Emad; Forman, Jeffrey D; Tekyi-Mensah, Samuel; Bolton, Susan; Hart, Kim

    2002-06-01

    The purpose of this study was to determine the outcome of patients receiving external beam radiation for an elevated postprostatectomy prostate-specific antigen (PSA) level. Between December 1991 and September 1998, 108 patients received definitive radiation therapy for elevated postprostatectomy PSA levels. The median dose of irradiation was 68 Gy (range, 48-74 Gy). During treatment, the PSA levels were checked an average of 5 times (range, 3-7 times). Prostate-specific antigen values were judged to decline or increase during treatment if they changed by more than 0.2 ng/mL. After treatment, biochemical failure was defined as a measurable or rising PSA > 0.2 ng/mL. Median follow-up was 51 months (range, 3-112 months). Fifty-eight patients (54%) had evidence of biochemical failure. The 3- and 5-year actuarial biochemical relapse-free (bNED) survivals for all patients were 55% and 39%, respectively. Upon univariate analysis, intratreatment PSA and preradiation PSA were significant predictors of bNED survival. Patients with a PSA level that decreased during treatment had a 5-year bNED survival of 43% compared to 10% in patients with an increasing PSA level (P = 0.0002). Using the preradiation therapy PSA value as a continuous variable, higher preradiation therapy PSA levels were associated with an increased risk of failure (P = 0.004). Cut points of pretreatment PSA were derived at 0.9 ng/mL and 4.2 ng/mL using the Michael Leblanc recursive partitioning algorithm. The 5-year bNED rate for patients with a preradiation therapy PSA or = 4.2 ng/mL (P = 0.0003). Patients with a Gleason score of 7 (P = 0.27). Other factors examined individually that did not reach statistical significance included time from surgery to radiation therapy, race, seminal vesicle involvement, pathological stage, surgical margin, and perineural invasion. Upon multivariate analysis, only preradiation therapy PSA (P < 0.001) and the PSA trend during radiation therapy (P < 0.001) were significant

  18. Cytokines and therapeutic oligonucleotides.

    Science.gov (United States)

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  19. Study on the Effects of Different Therapeutic Doses of Immunosuppressive Agents on the Growth and Development of Rats%不同治疗剂量的免疫抑制剂对大鼠生长发育的影响

    Institute of Scientific and Technical Information of China (English)

    陈林强; 何绿茵; 徐邦牢; 仉智; 林华欣; 李淼沅; 陈业辉

    2012-01-01

    Objective To observe the effects of different therapeutic doses of immunosuppressive agents on rat growth. Methods To establish different therapeutic doses of immunosuppressive agents in SD rat model, after renal transplantation, the first agent treatment doses of cyclosporine A (Cyclosporin A,CsA) (Tacrolimus,FK506) ,tacrolimus and rapamycin (Rapa-mycin,Rapa) were converted into the therapeutic dose of rats,respectively,by the formula. 25 mg/kg/d,0. 8 mg/kg/d and 2 mg/kg/d gastric feeding were set as drug intervention group, saline gastric feeding as the control group, 8 rats in each group. The rats were fed by the gastric feeding for 8 weeks. Each rat growth and body weight changes were observed. Results There were no significant difference of the rats weight before the experiment began. 8 weeks after modeling,cyclosporin A treated rats showed marked weight loss,anorexia,irritable,sparse hair. The control group,cyclosporine A (CsA) (FK506), tacrolimus and rapamycin (Rapa) treated rats showed increased weight, respectively, 339. 62± 11. 97 g, 296. 50±22. 69 g, 335. 30±17. 51 g and 342.56 + 15.29 g; weight gain were 158.75 + 15.68 g, 112. 24 ±20. 16 g, 154. 78 ± 11. 32 g,and 160. 91 + 13. 51g,respectively. Cyclosporin A (CsA) treated rats bodyweight growth was significantly lower than that of the control group (P0. 05). Conclusion cyclosporin A (CsA) affected the growth of rat more significantly but FK506 and Rapa had no significant effect on the rats weight.%目的 观察不同治疗剂量的免疫抑制剂对大鼠生长发育的影响.方法 建立不同治疗剂量的免疫抑制剂SD大鼠模型,按公式将肾移植术后环孢素A (Cyclosporin A,CsA)、他克莫司(Tacrolimus,FK506)和雷帕霉素(Rapamycin,Rapa)的首剂治疗剂量换算成大鼠的治疗剂量,分别用25mg/kg/天,0.8mg/kg/天和2mg/kg/天胃饲作为药物干预组,生理盐水胃饲作为对照组,每组8只,胃饲8周.观察并比较各组大鼠生长发育及

  20. Therapeutic drug monitoring of amoxicillin and cloxacillin

    Institute of Scientific and Technical Information of China (English)

    OTRIBUT; PTATTEVIN; MVERDIER; YLETULZO; CMICELET; HALLAIN; DBENTURE-FERRER

    2004-01-01

    AIM: Beta-lactams (BL) are broad-spectrum antibiotics currently used in number of infectious diseases and some infections need high dose of antibiotics. BL studied here are eliminated rather quickly by the kidney. A renal insufficiency involves an increase in BL concentrations. Therapeutic drug monitoring could help in adapting the target concentration. METHODS: We developed a rapid (less than 20 min), sensitive, and specific HPLC method

  1. Dose selection for prostate cancer patients based on dose comparison and dose response studies

    International Nuclear Information System (INIS)

    Purpose: To better define the appropriate dose for individual prostate cancer patients treated with three-dimensional conformal radiation therapy (3D CRT). Methods and Materials: Six hundred eighteen patients treated with 3D CRT between 4/89 and 4/97 with a median follow-up of 53 months are the subject of this study. The bNED outcomes were assessed by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. The patients were grouped into three groups by prostate-specific antigen (PSA) level (<10 ng/ml, 10-19.9 ng/ml, and 20+ ng/ml) and further subgrouped into six subgroups by favorable (T1, 2A and Gleason score ≤6 and no perineural invasion) and unfavorable characteristics (one or more of T2B, T3, Gleason 7-10, perineural invasion). Dose comparisons for bNED studies were made for each of the six subgroups by dividing patients at 76 Gy for all subgroups except the favorable <10 ng/ml subgroup, which was divided at 72.5 Gy. Five-year bNED rates were compared for the median dose of each dose comparison subgroup. Dose response functions were plotted based on 5-year bNED rates for the six patient groupings, with the data from each of the six subgroups divided into three dose groups. The 5-year bNED rate was also estimated using the dose response function and compares 73 Gy with 78 Gy. Results: Dose comparisons show a significant difference in 5-year bNED rates for three of the six subgroups but not for the favorable <10 ng/ml, the favorable 10-19.9 ng/ml, or the unfavorable ≥20 ng/ml subgroups. The significant differences ranged from 22% to 40% improvement in 5-year bNED with higher dose. Dose response functions show significant differences in 5-year bNED rates comparing 73 Gy and 78 Gy for four of the six subgroups. Again, no difference was observed for the favorable <10 ng/ml group or the unfavorable ≥20 ng/ml group. The significant differences observed in 5-year bNED ranged from 15% to 43%. Conclusions: Dose response varies by patient

  2. Engineering antibody therapeutics.

    Science.gov (United States)

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  3. Boron dose enhancement for Cf-252 brachytherapy

    International Nuclear Information System (INIS)

    Full text: Monte Carlo modelling of a Cf-252 source in water and in tissue has shown that there is a significant therapeutic advantage obtained if B-10 is present in the tumour cells. This study analyses the advantage in terms of therapeutic margin, defined as the distance from the border of the treatment volume where boron-loaded tumour cells will receive a therapeutic dose. Calculations were made with MCNP version 4a on a Pentium 60 MHz computer. Large voxel sizes allowed 70 minute runs to achieve statistical uncertainties of 5% or less for 100,000 source neutrons. Later runs with smaller voxels confirmed the accuracy of the initial calculations. Calculations were made for treatment volume radii up to 11 cm and 30 ppm boron-10. The therapeutic margin for radii in the range 3-9 cm is approximately 10% of the tumour radius. This results in a 30% increase in the volume inside which peripheral tumour cells may receive a therapeutic dose. The median therapeutic ratio within the therapeutic margin varied from 1.05 at 3 cm up to 1.25 at 10 cm. Thus there is little benefit for less advanced tumours with thickness less than 3 cm. However, cervical cancer frequently presents in an advanced state in Southeast Asia and in Aboriginal communities in Australia, partially attributable to low Pap smear screening rates. These conclusions support the development and testing of boron compounds in in vitro and in vivo models for cervical cancer

  4. Therapeutic effect of different dosing regimens of rmlL-12 on acute radiation sickness in mice%白介素12不同给药方案对急性放射病小鼠的治疗作用

    Institute of Scientific and Technical Information of China (English)

    王利; 王松雷; 曹务锐; 耿斌; 翟瑞仁; 逄朝霞; 张超; 余长林

    2013-01-01

    Objective: To study the therapeutic effect of different dosing regimens of recombinant murine interleu-kin 12(rmIL - 12) on the mice irradiated by γ -rays. Methods: Forty -two BALB/c mice were given 6.0Gy 60Co γ - rays total body irradiation and randomly assigned into irradiation control group,rmIL - 12 one dose and five doses treatment group. 20μg/kg of rmIL - 12 was administrated intraperitoneally 1 hour following irradiation in one dose treatment group, and was administrated every 3 days after irradiation for four times additionally in five doses treatment group. The general conditions of mice were observed twice a day, the changes in body weight, peripheral blood cell counts were examined once every three days, bone marrow cells were collected to perform colony cultivation on the 14th and 28th day after irradiation. Results: The general conditions of mice in rmIL - 12 treatment group were better than those of irradiation control group. The decline speed of platelet in rmIL - 12 one and five doses treatment group was significantly slower than that of control group. rmIL - 12 treatment significantly promoted platelet recovery, resulting in less profound nadirs(18.9% vs 8. 1% ,22.5% vs 8. 1% ,P0. 05). The white blood cell recovery speed in two treatment groups was faster than that of the irradiation control group(P<0.05) ,but there was no significant difference between two treatment groups. Semi - solid bone marrow cell culture also demonstrated that rmIL - 12 could stimulate bone marrow cells to form more CFU - Mix than those of the irradiation control group on 14th after irradiation(P <0. 01) ,and there were more CFU - GM and CFU - Mix in two rmIL - 12 treatment group than those of the irradiation control group on 28th after irradiation (P < 0.05, P< 0.01). Conclusion: 1 and 5 dosing regimens of rmIL - 12 can significantly accelerate the recovery of hematopoietic function , especially the recovery of megakaryocyte in acute radiation sickness mice.%目的:

  5. Crystalline dose of interventional radiologists; Dosis en cristalino de radiologicos intervencionistas

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez Concepcion, E.; Diaz Romero, F.; Catalan Acosta, A.; Hernandez Armas, J.

    2013-07-01

    The measured dose area product in radiology equipment used in angio radiology during different diagnostic and therapeutic can be used to estimate the value of the dose in the lens of doctors or medical personnel carrying out such interventions. (Author)

  6. Ondansetron. Therapeutic use as an antiemetic

    Energy Technology Data Exchange (ETDEWEB)

    Milne, R.J.; Heel, R.C. (Adis Drug Information Services, Auckland (New Zealand))

    1991-04-01

    Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the moderate doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics. 101 refs.

  7. Dose-dependent galactorrhea with quetiapine

    OpenAIRE

    Sethi, Sujata; Sharma, Manisha; Malik, Amit

    2010-01-01

    Quetiapine is an atypical antipsychotic agent with minimal propensity to induce hyperprolactinemia in standard therapeutic dosages. Despite that quetiapine is considered to be a prolactin-sparing atypical antipsychotic, hyperprolactinemia with related side effects may rarely be encountered in susceptible individuals. We report a case of quetiapine-induced hyperprolactinemia and galactorrhea in an adult female, which was dose-dependent.

  8. Lymphedema and Therapeutic Lymphangiogenesis

    Directory of Open Access Journals (Sweden)

    Yukihiro Saito

    2013-01-01

    Full Text Available Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The recent impressive expansion of knowledge on the molecular mechanisms governing lymphangiogenesis provides new possibilities for the treatment of lymphedema. This review highlights the lymphatic biology, the pathophysiology of lymphedema, and the therapeutic lymphangiogenesis using hepatocyte growth factor.

  9. Pluristem Therapeutics, Inc.

    Science.gov (United States)

    Prather, William

    2008-01-01

    Pluristem Therapeutics, Inc., based in Haifa, Israel, is a regenerative, biotherapeutics Company dedicated to the commercialization of nonpersonalized (allogeneic) cell therapy products. The Company is expanding noncontroversial placental-derived mesenchymal stem cells via a proprietary 3D process, named PluriX, into therapeutics for a variety of degenerative, malignant and autoimmune disorders. Pluristem will be conducting Phase I trials in the USA with its first product, PLX-I, which addresses the global shortfall of matched tissue for bone marrow transplantation by improving the engraftment of hematopoietic stem cells contained in umbilical cord blood. PMID:18154467

  10. Optimizing lithium dosing in hemodialysis

    DEFF Research Database (Denmark)

    Bjarnason, N H; Munkner, R; Kampmann, J P;

    2006-01-01

    We studied a 62-year-old female hemodialysis patient during initiation and maintenance of lithium carbonate therapy. Three different methods were applied to estimate the regimen: a scenario based on volume of distribution (V(d)), a scenario based on glomerular filtration rate (GFR), and a scenario...... estimates. Furthermore, the maintenance dose estimated from the central compartment (V1) led to plasma concentrations within the therapeutic range. Thus, a regimen where 12.2 mmol lithium was given after each hemodialysis session resulted in stable between-dialysis plasma lithium concentrations...

  11. Eficacia clínica de oxicodona: La presentación de 5 mg en el esquema terapéutico del ascensor analgésico Clinical Effectiveness of oxicodone: The 5 mg dose in the analgesic elevator therapeutic scheme

    Directory of Open Access Journals (Sweden)

    M. A. Vidal

    2008-04-01

    ía eliminar el principal obstáculo para llevar a la práctica el "Ascensor Analgésico".Introduction. Oxicodone has been a semisynthetic opioide derived from thebaine with múltiple actions similar to morphine, used actually clinical for more than 80 years. Its main therapeutic action is the analgesia; and to a lesser extent sedative action. To dose lower than the necessary one to produce analgesia, can act on the center of the cough. The objective of this article is to make a review of the characteristics of oxicodone: its pharmacological properties, tolerability and mainly its clinical effectiveness in the different types of pain and with the different presentations that exist at the moment in the market. The reviewed articles come from the data base of Medline and Cochrane. Clinical effectiveness. Numerous studies guarantee the effectiveness of oxicodone in the treatment of the different types of pain. Nevertheless these studies have their limitations. The studies that are based on the use of oxicodone in nononcological chronic pain are positive comparative studies to placebo. As far as the oncological pain, the comparative clinical tests from morphine and hidromorphone, oxicodone has presented advantages in effectiveness, and safety. Also revisions have been carried out on the matter in which it scores at oxicodone like a good alternative to morphine. Discussion. Oxicodone is a good alternative for the treatment of the moderate-severe pain, for a program of opioids rotation of since it has an excellent balance between analgesia and toxicity. Oxicodone prolonged release 5 mg, is very useful like initial dose to titrate opioids, being climbed dose at 48 hours, with which the incidence of indirect effect is diminished and diminishes the risk of therapeutic abandonment that these entail. With this approach one would be able to eliminate the main obstacle to put in practice the "Analgesic Elevator" theory.

  12. Emerging therapeutic options for asthma.

    Science.gov (United States)

    Colice, Gene L

    2011-04-01

    Asthma is characterized by eosinophilic airway inflammation and elevated serum immunoglobulin E (IgE) levels. Due to these pathologic features, the foundation of asthma treatment has historically been anti-inflammatory therapy with inhaled corticosteroids (ICSs). Numerous factors in addition to IgE and eosinophils, however, likely play important roles in mediating the airway inflammatory response characteristic of asthma. ICSs are effective therapy for some patients with persistent asthma, but clinical trials have shown that even increasing doses of ICSs under carefully controlled situations does not always result in acceptable asthma control. Consequently, other classes of medications, in addition to ICSs, are recommended in those patients with more severe asthma. The class of medication most commonly used in more severe asthma, along with ICSs, is long-acting inhaled beta2-agonists, but leukotriene modifying agents and anti-IgE monoclonal antibodies may also be used. Agents such as tiotropium, a long-acting inhaled anti-muscarinic agent, and those aimed at inhibiting cytokines, such as mepoluzimab, daclizumab, and etanercept, hold promise in the treatment of asthma. Other agents under investigation include phosphodiesterase type 4 inhibitors and oligonucleotides. Bronchial thermoplasty, a nonpharmacologic option, may also be beneficial in patients with poorly controlled asthma. As our understanding of the complex pathophysiology of asthma increases, it will enable the development of novel therapeutic approaches for patients who are not responding well to traditional treatments. Although more studies are necessary to ensure the efficacy and safety of both pharmacologic and nonpharmacologic approaches, there is future promise for therapeutic advances in severe, persistent asthma. PMID:21761958

  13. Dosing dilemmas in obese children.

    Science.gov (United States)

    Mulla, H; Johnson, T N

    2010-08-01

    With the epidemic of childhood obesity, it is not uncommon for prescribers to puzzle over an appropriate drug dose for an obese child. Defining the optimum therapeutic dose of a drug relies on an understanding of pharmacokinetics and pharmacodynamics. Both these processes can be affected by body composition and the physiological changes that occur in obese children. As a rule of thumb, 75% of excess weight in obese subjects is fat mass, and the remainder lean mass. Although it is reasonable to assume that increases in fat mass alter the distribution of lipophilic drugs and increases in lean mass alter drug clearance, good quality and consistent clinical data supporting these assumptions are lacking for the majority of drugs. The relatively few clinical studies that have evaluated the impact of obesity have often been limited by poor design and insufficient sample size. Moreover, clinical studies conducted during drug development rarely include (or are required to include) obese subjects. Guidance on dosing obese children ought to be provided by drug manufacturers. This could be achieved by including obese patients in studies where possible, enabling the effect of body size on pharmacotherapy to be evaluated. This approach could be further augmented by the use of physiologically based-pharmacokinetic models during early (preclinical) development to predict the impact of obesity on drug disposition, and subsequent clinical studies later in development to provide confirmatory proof. In the meantime, for the majority of drugs already prescribed in children, particularly those where the therapeutic range is narrow or there is significant toxicity, the lack of a validated body size descriptor to use at the bedside means the choice of dose will rely on empirical experience and application of the precautionary principle. PMID:20585055

  14. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

  15. Optimizing Pediatric Esmolol Dosing Using Computerized Practitioner Order Entry

    OpenAIRE

    Chao, Tihua; Perry, James C.; Romanowski, Gale L.; Tremoulet, Adriana H.; Capparelli, Edmund V

    2014-01-01

    OBJECTIVES: The aims of this study were to 1) describe the cardiovascular dose-response of esmolol and dose-limiting adverse effects in pediatric patients; 2) assess an institutional guideline for protocol adherence, efficacy, and achievement of therapeutic targets for pediatric patients with tachyarrhythmias or systemic hypertension; and 3) revise the protocol accordingly.

  16. Therapeutic effect and safety of half dose tirofiban combined PCI in patients with acute myocardial infarction complicated early renal insufficiency%半剂量替罗非班联合PCI对早期肾功能不全急性心肌梗死患者的疗效及安全性

    Institute of Scientific and Technical Information of China (English)

    沈冲; 方雪花; 赵炳朕; 余清; 马飞; 张伟; 高德全; 赵雪东

    2012-01-01

    目的:观察半剂量替罗非班联合经皮冠脉介入治疗(PCI)对合并早期肾功能不全急性心肌梗死(AMI)患者的疗效及安全性.方法:选择合并早期肾功能不全的AMI患者55例作为肾功能不全组,56例肾功能正常的AMI患者作为AMI对照组,两组均应用常规抗凝、抗血小板治疗,肾功能不全组于穿刺成功后开始应用半剂量替罗非班,AMI对照组全量应用替罗非班.比较两组间住院期主要不良心血管事件(MACE),出血、血小板减少发生率及对比剂肾病发生率的差异.结果:与AMI对照组比较,肾功能不全组3支病变比例(21.1%比43.6%)、术后肌酸激酶峰值浓度[(1863.1±86.7)IU/L比(2371.5±126.3)IU/L]明显升高(P均<0.05);两组术后TIMI 3级血流率、校正的TIMI计帧数和Blush 3级率未见显著性差异(P>0.05),术后2h心电图相关导联ST段下降幅度及住院期间的MACE发生率亦无显著性差异(P>0.05),出血事件发生率和血小板减少发生率亦无显著差异(P>0.05).对比剂肾病:AMI对照组无发生,肾功能不全组有3例发生(0%比5.45%,P<0.05).结论:合并早期肾功能不全的急性心肌梗死患者三支病变比例高,半剂量替罗非班联合PCI能有效再灌注心肌,降低住院心血管事件发生,未见明显出血及血小板减少发生率增加,但需警惕对比剂肾病的发生,术后应加强监测与干预.%To investigate therapeutic effect and safety of half dose tirofiban combined percutaneous coronary intervention (PCI) on patients with acute myocardial infarction (AMI) complicated early renal insufficiency. Methods: A total of 55 AMI patients with early renal insufficiency were enrolled as renal insufficiency group and 56 AMI patients with normal renal function were regard as AMI control group. Both groups received routine anticoagulant and antiplatelet therapy, renal insufficiency group received half dose tirofiban after successful puncture while AMI control group

  17. Single dose NTBC-treatment of hereditary tyrosinemia type I.

    Science.gov (United States)

    Schlune, A; Thimm, E; Herebian, D; Spiekerkoetter, U

    2012-09-01

    NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3cyclohexanedione) is the mainstay of treatment in tyrosinemia type 1 (HT 1). The current recommendation is to divide the total daily dose of NTBC into two doses. We monitored the plasma NTBC concentrations in a series of seven patients who were changed from multiple divided doses to a single daily dose of NTBC. Two additional patients were started on a single daily dose of NTBC after the diagnosis of HT 1 was established. In three patients, NTBC kinetics were performed over 6 and 24 hours, respectively. The use of multiple divided doses or a single daily dose did not significantly affect plasma NTBC concentrations or the mean daily dose needed to attain therapeutic plasma NTBC concentrations. Moreover, kinetic studies demonstrated that plasma NTBC concentrations were completely stable over a period of 24 hours with a single dose regimen, as expected given the known NTBC plasma half life of 54 hours. Although these preliminary results need to be confirmed in more patients, our findings show that administration of NTBC in a single daily dose may be as effective as a multiple-dose regimen in reaching therapeutic plasma NTBC concentrations and suppressing succinylacetone formation in patients with HT 1. In fact, single dose treatment may increase patients' compliance with the drug treatment and improve metabolic control. PMID:22307209

  18. Evaluation of radiation doses and dose conversion coefficients for pediatric cardiac catheterization procedures

    International Nuclear Information System (INIS)

    Pediatric cardiac catheterization covers both diagnostic and therapeutic procedures that range from simple to complex and can subject pediatric patients to varying radiation doses. There is limited information on radiation doses delivered by pediatric cardiac catheterization procedures and there is no recommended reference dose levels established yet. The study aims to determine the variation in patient radiation doses in terms of dose area product values and effective doses; determine factors that contribute to high doses to optimize protection; and determine the effective dose conversion coefficient. It is also aimed to provide data to help in the establishment of reference dose levels. A total of 761 pediatric patients belonging to age groups 0, 1, 5 and 10 years who undergo diagnostic and three selected therapeutic procedures at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia are included in the study. Therapeutic procedures include COA, PDA and pulmonary procedures. Fluoroscopy and cine radiography are used in all procedures. Patient demography (weight, age, gender and height), radiographic technique factors, fluoroscopy and cine time, frame rate, and dose area product values are taken from patients records. Results show that the kVp varies by ± 1 kVp between procedures and by ± 6 kVp between AP and oblique + lateral projection for all procedures. The mA for lateral and oblique is about 40-70% higher than for AP. Effective doses for each procedure are estimated from the DAP values. The mean DAP and effective dose per procedure are analyzed for correlation with patient equivalent cylindrical diameter, weight, fluoroscopy time and number of frames. Initial results show that age group 0 and 1 year old have the highest mean value for effective dose (11.3 and 13.8 mSv respectively) for pulmonary procedure. Pooling all ages for each procedure, the pulmonary and PDA procedures gave the highest mean values for effective dose (10 and 8.2 m

  19. 乳腺癌分子分型与多西他赛密集新辅助化疗疗效及预后的关系研究%Relationship of Molecular Subtypes and Therapeutic Effect and Prognosis of Dose Dense Docetaxel Neoadjuvant Chemotherapy in Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    刘秋明; 曹亚丽; 吴晓波; 夏勇; 涂剑宏; 欧阳倩雯; 周平; 胡平华; 陈军

    2012-01-01

    Objective To investigate the relationship between different molecular subtypes and the therapeutic effect and prognosis of dose dense docetaxel neoadjuvant chemotherapy in breast cancer. Methods 82 breast cancer patients admitted to our hospital from March 2007 to March 2010 were given four cycles of docetaxel chemotherapy ( 75 mg/m , with two weeks as a cycle ), followed by surgical operation. After operation, the patients were given four cycles of EC chemotherapy ( with EPI 75 mg/m , CTX 600 mg/m and two weeks as a cycle ) . Immunohistochemical studies and fluorescence in -situ hybridization were performed to detect the expression of estrogen receptor ( ER ), progesterone receptor ( PR ), Her - 2 and Ki67 of breast cancer before treatment. The patients were classified into 4 subtypes: luminal A, luminal B, Her -2 + and triple negative. The therapeutic effect and prognosis of the four subtypes after dose dense docetaxel neoadjuvant chemotherapy were analyzed. Results Of the total 82 patients, the overall response rate ( RR ) was 89. 0% ( 73/82 ), including 17 cases of complete response ( CR ), 56 cases of partial response ( PR ), 9 cases of stable disease ( SD ) and no progression of disease ( PD ) . FISH were performed to detect 11 cases of IHC scores of 2 + . There were 5 cases for the overexpression of Her -2. According to the results of immunohis- tochemical studies and FISH method on the expression of ER, PR, Her -2 and Ki67, there were 39 cases ( 47. 6% ) of Luminal A, 19 cases ( 23. 2% ) of Luminal B, 11 cases ( 13. 4% ) of Her - 2 + and 13 cases ( 15. 9% ) of triple negative. The age, tumor size, lymph node metastasis, histological type and surgical style among breast cancer patients with different molecular subtypes showed no statistically significant differences ( P > 0. 05 ) . The RR of luminal A, luminal B, Her - 2 + and triple negative were 84. 6% ( 33/39 ), 84. 2% ( 16/19 ), 100. 0% ( 11/11 ) and 100. 0% ( 13/13 ) respectively, and the difference was

  20. Multistage vector (MSV) therapeutics.

    Science.gov (United States)

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-12-10

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  1. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity......Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... and hence adjuvants are included to enhance and direct the immune response. Although the vaccine has been tested in ART naïve individuals, we recommend future testing of the vaccine during (early started) ART that improves immune function and to select individuals likely to benefit. Peptides representing...

  2. Lymphedema and Therapeutic Lymphangiogenesis

    OpenAIRE

    Yukihiro Saito; Hironori Nakagami; Yasufumi Kaneda; Ryuichi Morishita

    2013-01-01

    Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The r...

  3. Polycyclic peptide therapeutics.

    Science.gov (United States)

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases. PMID:23355488

  4. Benchmark Dose Modeling

    Science.gov (United States)

    Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...

  5. Influence of pH on the /sup 14/C-labelling pattern after photosynthesis of suspended leaf slices and isolated mesophyll cells from chenopodium album in NaH/sup 14/CO/sub 3/

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, G.; Guenther, G. (Paedagogische Hochschule Karl Liebknecht, Potsdam (German Democratic Republic). Sektion Chemie/Biologie)

    1983-01-01

    Photosynthetic fixation of /sup 14/C from solutions of NaH/sup 14/CO/sub 3/ (at constant concentrations of free CO/sub 2/) by suspended leaf slices or isolated mesophyll cells from Chenopodium album is increased with increasing pH. Above all, the incorporation of radioactivity into amino acids and malate is stimulated. A direct uptake of HCO/sub 3/ ions and its fixation by PEP carboxylase is suggested. Isolated mesophyll cells showed at pH 7.3 a higher rate of photosynthesis than at pH 5.0.

  6. Comparative studies on anthraquinone retention following the soda/anthraquinone process using 14C-labelled anthraquinone, and mode of action of anthraquinone on lignins and lignin model components

    International Nuclear Information System (INIS)

    This dissertation contributes to the clarification of the following questions: how much of the additive is retained in cellulose following soda/anthraquinone-wood pulping; how much anthraquinone can be detected after extraction studies and after a conventional CEHD-bleaching treatment; can differences be detected between soda lignins and soda/anthraquinone lignins with respect to analytical data, spectroscopie characteristics and macromolecular properties; and how do dimeric lignin models with #betta#-arylether structure behave in decomposition studies using the soda/anthraquinone process. (orig./MG)

  7. Studies on the percutaneous absorption of /sup 14/C-labelled flurbiprofen, (1). Absorption, distribution around the spread site, metabolism and excretion of /sup 14/C-Flurbiprofen in swine

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Takeo; Nagao, Soshichi (Nihon Univ., Tokyo. Coll. of Agriculture and Veterinary Medicine)

    1982-03-01

    A 1% ointment of C/sup 14/-labelled 2-(2-fluoro-4-biphenylyl) propionic acid (FP) was applied onto the depilated backs of swines. A relatively large amount of C/sup 14/-FP was absorbed percutaneously. The drug concentration in the blood attained a peak of 0.097 ..mu..g/ml 12 hours after drug administration, after which it decreased rapidly to 11.3% of the peak concentration. High concentration of C/sup 14/FP was detected in the skin, its concentration being particularly high in the epidermis and corium, which shows that there were superficial dispersion and residue. The drug concentration in the muscle was low, which shows that there was little three-dimensional dispersion. The cumulative urinary excretion of the drug 120 hours after drug application was 16.7%, and the cumulative fecal excretion was 2.6%, the ratio of excretion into the urine to that into the feces being 6 : 1. The unchanged form of the drug and 3 metabolites were detected in the urine.

  8. Synthesis of [sup 14]C labelled electrophilic ligands of the colchicine binding site of tubulin: chloroacetates of demethylthiocolchicines and of N-acetylcolchinol; isothiocyanate of 9-deoxy-N-acetylcolchinol

    Energy Technology Data Exchange (ETDEWEB)

    Boye, O.; Brossi, A. (NIDDK (United States). Lab. of Structural Biology); Getahun, Z.; Grover, S.; Hamel, E. (National Inst. of Health, Bethesda, MD (United States))

    1993-01-01

    [sup 14]C-Chloroacetates of 2-demethylthiocolchicine 7 and of 3-demethylthiocolchicine 8 were synthesized and found to covalently bind with high specificity to the [beta]-subunit of tubulin. The [sup 14]C-chloroacetate of N-acetylcolchinol and the [sup 14]C-isothiocyanate were also prepared and found to react covalently with tubulin but in a nonspecific manner. With the radiolabelled chloroacetates 7 and 8 two compounds are now available to further characterize the colchicine binding site on the [beta] subunit of tubulin. (author).

  9. Therapeutic cloning in the mouse

    OpenAIRE

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of d...

  10. Concept for quantifying the dose from image guided radiotherapy

    International Nuclear Information System (INIS)

    Radiographic image guidance is routinely used for patient positioning in radiotherapy. All radiographic guidance techniques can give a significant radiation dose to the patient. The dose from diagnostic imaging is usually managed by using effective dose minimization. In contrast, image-guided radiotherapy adds the imaging dose to an already high level of therapeutic radiation which cannot be easily managed using effective dose. The purpose of this work is the development of a concept of IGRT dose quantification which allows a comparison of imaging dose with commonly accepted variations of therapeutic dose. It is assumed that dose variations of the treatment beam which are accepted in the spirit of the ALARA convention can also be applied to the additional imaging dose. Therefore we propose three dose categories: Category I: The imaging dose is lower than a 2 % variation of the therapy dose. Category II: The imaging dose is larger than in category I, but lower than the therapy dose variations between different treatment techniques. Category III: The imaging dose is larger than in Category II. For various treatment techniques dose measurements are used to define the dose categories. The imaging devices were categorized according to the measured dose. Planar kV-kV imaging is a category I imaging procedure. kV-MV imaging is located at the edge between category I and II and is for increasing fraction size safely a category I imaging technique. MV-MV imaging is for all imaging technologies a category II procedure. MV fan beam CT for localization is a category I technology. Low dose protocols for kV CBCT are located between category I and II and are for increasing fraction size a category I imaging technique. All other investigated Pelvis-CBCT protocols are category II procedures. Fan beam CT scout views are category I technology. Live imaging modalities are category III for conventional fractionation, but category II for stereotactic treatments. Dose from radiotherapy

  11. New horizons for therapeutic nuclear medicine in 1981

    Energy Technology Data Exchange (ETDEWEB)

    Beierwaltes, W.H.

    1981-06-01

    The therapeutic approach of internally administered radiopharmaceuticals offers the potential to outmode the present approaches of conventional radiation therapy and chemotherapy because of three characteristics: 1. The therapeutic use of radiopharmaceuticals may deliver as much as orders of magnitude larger rad doses than conventional radiation therapy to target tissues, selectively irradiating these tissues internally in one radiation dose. 2. The therapeutic use of radiopharmaceuticals is followed by a lower incidence of leukemia and other cancers. 3. The treatment is comparatively noninvasive and nontraumatic. We can now make this rather strong statement with fairly firm conviction because Na/sup 131/I has been used since 1946 (33 years) to treat almost a million patients for hyperthyroidism (a) and in approximately 5000 patients for well-differentiated thyroid cancer (b); NaH2PO4(P-32) has been used for 35 years to treat approximately 25,000 patients with polycythemia vera (3-5).

  12. New horizons for therapeutic nuclear medicine in 1981

    Energy Technology Data Exchange (ETDEWEB)

    Beierwaltes, W.H.

    1981-06-01

    The therapeutic approach of internally administered radiopharmaceuticals offers the potential to outmode the present approaches of conventional radiation therapy and chemotherapy because of three characteristics: (1) the therapeutic use of radiopharmaceuticals may deliver as much as orders of magnitude larger rad doses than conventional radiation therapy to target tissues, selectively irradiating these tissues internally in one radiation dose; (2) the therapeutic use of radiopharmaceuticals is followed by a lower incidence of leukemia and other cancers; (3) the treatment is comparatively noninvasive and nontraumatic. It is now possible to make this rather strong statement with fairly firm conviction because Na/sup 131/I has been used since 1946 to treat almost a million patients for hyperthyroidism (a) and in approximately 5000 patients for well-differentiated thyroid cancer (b); NaH/sub 2/PO/sub 4/ (P-32) has been used for 35 years to treat approximately 25,000 patients with polycythemia vera.

  13. Therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  14. Pneumothorax following therapeutic thoracentesis

    International Nuclear Information System (INIS)

    The authors retrospectively studied 319 patients undergoing therapeutic thoracentesis. Of these, 223 patients had malignant pleural effusions and 96 had nonmalignant and noninfected collections. The effusions ranged from 100 to 4,000 mL in size. All patients presented with pain and/or respiratory compromise prompting the need for drainage. Overall there was a t% (22 of 319) incidence of pneumothorax. In six patients (3%) chest tube placement was necessary. Four of these six patients were successfully managed with 7 - 16-French catheters and a Heimlich valve. Persistent pneumothorax in two cases required placement of large, 28-F chest tubes supplemented with Pleura-vac drainage and hospital admission. There was a subset of nine patients with malignant effusions and lymphangitic spread who developed large but asymptomatic pneumothoraces. All but 5% of these patients required no therapy for pneumothorax. The authors' results suggest that pneumothoraces following therapeutic thoracentesis can be managed within the radiology department. The prevalence, mechanism, and management of pneumothoraces in these patients is discussed

  15. Therapeutic nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Baum, Richard P. (ed.) [ENETS Center of Excellence, Bad Berka (Germany). THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging

    2014-07-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  16. Engineering therapeutic protein disaggregases

    Science.gov (United States)

    Shorter, James

    2016-01-01

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  17. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  18. [Therapeutic education didactic techniques].

    Science.gov (United States)

    Valverde, Maite; Vidal, Mercè; Jansa, Margarida

    2012-10-01

    This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective.

  19. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    and the drug which increased the potency of the conjugates significantly. A different approach to drug delivery is that of surface mediated drug delivery. Hydrogels of poly(vinyl alcohol) has shown great promise in this regard. The chemical opportunities of this polymer are explored through the virtues...... of reversible-addition-fragmentation chain transfer polymerization, which not only controls the size of polymer, but also allows the introduction of a terminal amine on the polymer which can be used for further conjugation. This has allowed for not only fluorescent labeling of the polymer, but also protein......The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...

  20. Homocystinuria: Therapeutic approach.

    Science.gov (United States)

    Kumar, Tarun; Sharma, Gurumayum Suraj; Singh, Laishram Rajendrakumar

    2016-07-01

    Homocystinuria is a disorder of sulfur metabolism pathway caused by deficiency of cystathionine β-synthase (CBS). It is characterized by increased accumulation of homocysteine (Hcy) in the cells and plasma. Increased homocysteine results in various vascular and neurological complications. Present strategies to lower cellular and plasma homocysteine levels include vitamin B6 intake, dietary methionine restriction, betaine supplementation, folate and vitamin B12 administration. However, these strategies are inefficient for treatment of homocystinuria. In recent years, advances have been made towards developing new strategies to treat homocystinuria. These mainly include functional restoration to mutant CBS, enhanced clearance of Hcy from the body, prevention of N-homocysteinylation-induced toxicity and inhibition of homocysteine-induced oxidative stress. In this review, we have exclusively discussed the recent advances that have been achieved towards the treatment of homocystinuria. The review is an attempt to help clinicians in developing effective therapeutic strategies and designing novel drugs against homocystinuria. PMID:27059523

  1. On being therapeutic.

    Science.gov (United States)

    Greben, S E

    1977-11-01

    Psychotherapy is both an art and a science. The art deserves as careful study as does the science. In this paper the author puts forward the view that the effectiveness of psychotherapy is dependent to a marked degree upon certain innate characteristics of the therapist: these include his character structure, his personal values, and his spontaneous personality style. In order to explore this thesis, the author examines what has been written about some successful and well-known psychotherapists, by their patients, their colleagues, and their friends. He concludes that these therapists strongly evidenced the following characteristics: empathy and concern, caring and protectiveness, warmth, therapeutic forcefulness, expectation of improvement, freedom from despair, reliability, friendliness and respectfulness. It is felt that such factors in the therapist must be taken into account in order to achieve a view of psychotherapy which is not reductionistic. PMID:589551

  2. Therapeutic Strategies in HCC: Radiation Modalities

    Science.gov (United States)

    Gallicchio, R.; Nardelli, A.; Mainenti, P.; Nappi, A.; Capacchione, D.; Simeon, V.; Sirignano, C.; Abbruzzi, F.; Barbato, F.; Landriscina, M.

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  3. Therapeutic Strategies in HCC: Radiation Modalities

    Directory of Open Access Journals (Sweden)

    R. Gallicchio

    2016-01-01

    Full Text Available Patients with hepatocellular carcinoma (HCC comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE and transarterial metabolic radiotherapy (TAMR have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment.

  4. Therapeutic Strategies in HCC: Radiation Modalities.

    Science.gov (United States)

    Gallicchio, R; Nardelli, A; Mainenti, P; Nappi, A; Capacchione, D; Simeon, V; Sirignano, C; Abbruzzi, F; Barbato, F; Landriscina, M; Storto, G

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment.

  5. Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases.

    Science.gov (United States)

    Heard, Kennon; Bui, Alison; Mlynarchek, Sara L; Green, Jody L; Bond, G Randall; Clark, Richard F; Kozer, Eran; Koff, Raymond S; Dart, Richard C

    2014-01-01

    Liver injury has been reported in children treated with repeated doses of acetaminophen. The objective of this study was to identify and validate reports of liver injury or death in children younger than 6 years who were administered repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data, peer-reviewed literature, US Food and Drug Administration Adverse Event Reports, and US Manufacturer Safety Reports describing adverse effects after acetaminophen administration. Reports that described hepatic abnormalities (description of liver injury or abnormal laboratory testing) or death after acetaminophen administration to children younger than 6 years were included. The identified reports were double abstracted and then reviewed by an expert panel to determine if the hepatic injury was related to acetaminophen and whether the dose of acetaminophen was therapeutic (≤75 mg/kg) or supratherapeutic. Our search yielded 2531 reports of adverse events associated with acetaminophen use. From these cases, we identified 76 cases of hepatic injury and 26 deaths associated with repeated acetaminophen administration. There were 6 cases of hepatic abnormalities and no deaths associated with what our panel determined to be therapeutic doses. A large proportion of cases could not be fully evaluated due to incomplete case reporting. Although we identified numerous examples of liver injury and death after repeated doses of acetaminophen, all the deaths and all but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day. This study suggests that the doses of less than 75 mg/kg per day of acetaminophen are safe for children younger than 6 years.

  6. Study and evaluation of radiometry in photo therapeutic treatment of the neonatal hyperbilirubinaemia

    International Nuclear Information System (INIS)

    Phototherapy is a procedure established more than 50 years ago in the treatment of the newborn jaundice. However there is no a standard method to quantify the photo therapeutic dose in published clinical studies, hindering the comparison of previous studies on photo therapeutic effectiveness, as well as the establishment of safe and predictable doses. The photo therapeutic dose depends, among other factors, on the effective mean irradiance produced by the photo therapeutic unit. There are no standard procedures, however, neither to quantify the effective irradiance, nor to estimate the mean effective irradiance. As a consequence, large measurement variations in a same photo therapeutic unit are observed using different commercially available radiometers, as a consequence of the vast diversity of spectral responsivities of the instruments. An objective of this work was to adapt and to apply the bases of the wideband ultraviolet radiometry to quantify the available irradiance from photo therapeutic units, establishing procedures that allow us to compare measured irradiances from different sources, using radiometers presenting different spectral responsivities. Another objective was to characterize samples of photo therapeutic units commonly used, focusing the problem of the estimation of the effective mean irradiance from photo therapeutic units, proposing a method to estimate of the effective irradiance from focused sources. The experimental results allow us to conclude that it is not only necessary to standardize the photo therapeutic radiometry, but also the method of estimation of the effective mean irradiance. (author)

  7. Responses of rat R-1 cells to low dose rate gamma radiation and multiple daily dose fractions

    International Nuclear Information System (INIS)

    Multifraction irradiation may offer the same therapeutic gain as continuous irradiation. Therefore, a comparison of the efficacy of low dose rate irradiation and multifraction irradiation was the main objective of the experiments to be described. Both regimens were tested on rat rhabdomyosarcoma (R-1) cells in vitro and in vivo. Exponentially growing R-1 cells were treated in vitro by a multifraction irradiation procedure with dose fractions of 2 Gy gamma radiation and time intervals of 1 to 3 h. The dose rate was 1.3 Gy.min-1. The results indicate that multifractionation of the total dose is more effective with respect to cell inactivation than continuous irradiation. (Auth.)

  8. New therapeutics for osteoporosis.

    Science.gov (United States)

    Ng, Kong Wah; Martin, T John

    2014-06-01

    Two new approaches for the treatment of osteoporosis are summarized, each having arisen out of important new discoveries in bone biology. Odanacatib (ODN) inhibits the enzyme, cathepsin K, that is essential for the resorbing activity of osteoclasts. It is effective in preventing ovariectomy-induced bone loss in preclinical studies, and a phase II clinical study has shown inhibition of resorption sustained over five years. Outcome of a phase III study is awaited. The finding from mouse and human genetics that Wnt signaling is a powerful inducer of bone formation led to developments aimed at enhancing this pathway. Of the several approaches towards this, the most advanced is with a neutralizing antibody against sclerostin, the osteocyte-derived inhibitor of Wnt signaling. Preclinical studies show a powerful bone anabolic effect, and a clinical phase II study shows dose-dependent increases in bone formation and decreases in bone resorption markers. PMID:24699340

  9. FAQ about Recreational Therapy/Therapeutic Recreation

    Science.gov (United States)

    ... is the relationship between recreational therapy and therapeutic recreation? Therapeutic Recreation is the field ​​Recreational ... for individuals with disabilities." About the American Therapeutic Recreation Association: The American Therapeutic Recreation Association (ATRA) is ...

  10. Radiation dose assessment in nuclear medicine

    International Nuclear Information System (INIS)

    Radionuclides are used in nuclear medicine in a variety of diagnostic and therapeutic procedures. Recently, interest has grown in therapeutic agents for a number of applications in nuclear medicine. Internal dose models and methods have been in use for many years, are well established and can give radiation doses to stylized models representing reference individuals. Kinetic analyses need to be carefully planned, and dose conversion factors should be chosen that are most similar to the subject in question and that can then be tailored to be more patient specific. Such calculations, however, are currently not relevant in patient management in internal emitter therapy, as they are not sufficiently accurate or detailed to guide clinical decision making. Great strides are being made at many centres regarding the use of patient image data to construct individualized voxel based models for more detailed and patient specific dose calculations.These recent advances make it likely that the relevance will soon change to be more similar to that of external beam treatment planning. (author)

  11. Therapeutic cloning: The ethical limits

    International Nuclear Information System (INIS)

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

  12. Clinical applications of therapeutic phlebotomy

    Science.gov (United States)

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. PMID:27486346

  13. Clinical applications of therapeutic phlebotomy.

    Science.gov (United States)

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program.

  14. Plasmids encoding therapeutic agents

    Science.gov (United States)

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  15. [Liver metastasis: therapeutic strategy].

    Science.gov (United States)

    Gennari, L; Doci, R; Bignami, P

    1996-01-01

    The liver is one of the most frequent sites of metastatic growth, in particular from digestive malignancies (DM). The first goal is to reduce the incidence of metastases. Adjuvant systemic chemotherapies have been demonstrated to reduce the recurrence rate and to improve survival in Dukes C colon cancer. Fluorouracil is the pivot of adjuvant treatment modulated by Leucovorin or Levamisol. A short postoperative administration of fluorouracil by intraportal route has been tested, but the results are controversial. Adjuvant treatments for different DM are under investigation. When hepatic metastases are clinically evident, therapeutic decisions depend on several factors: site and nature of primary, extent of hepatic and extrahepatic disease, patient characteristics, efficacy of treatments. A staging system should be adopted to allow a rational approach. In selected cases a locoregional treatment can achieve consistent results. Hepatic Intrarterial Chemotherapy (HIAC) for colorectal metastases achieves objective responses in more than 50% of patients. Survival seems positively affected. When feasible, Ro hepatic resection is the most effective treatment, five-year survival rate being about 30% when metastases are from colorectal cancer. Since the liver is the most frequent site of recurrence after resection, repeat resection have been successfully performed. PMID:9214269

  16. Enjebi Island dose assessment

    International Nuclear Information System (INIS)

    We have updeated the radiological dose assessment for Enjebi Island at Enewetak Atoll using data derived from analysis of food crops grown on Enjebi. This is a much more precise assessment of potential doses to people resettling Enjebi Island than the 1980 assessment in which there were no data available from food crops on Enjebi. Details of the methods and data used to evaluate each exposure pathway are presented. The terrestrial food chain is the most significant potential exposure pathway and 137Cs is the radionuclide responsible for most of the estimated dose over the next 50 y. The doses are calculated assuming a resettlement date of 1990. The average wholebody maximum annual estimated dose equivalent derived using our diet model is 166 mremy;the effective dose equivalent is 169 mremy. The estimated 30-, 50-, and 70-y integral whole-body dose equivalents are 3.5 rem, 5.1 rem, and 6.2 rem, respectively. Bone-marrow dose equivalents are only slightly higher than the whole-body estimates in each case. The bone-surface cells (endosteal cells) receive the highest dose, but they are a less sensitive cell population and are less sensitive to fatal cancer induction than whole body and bone marrow. The effective dose equivalents for 30, 50, and 70 y are 3.6 rem, 5.3 rem, and 6.6 rem, respectively. 79 refs., 17 figs., 24 tabs

  17. Neutron absorbed dose in a pacemaker CMOS

    Energy Technology Data Exchange (ETDEWEB)

    Borja H, C. G.; Guzman G, K. A.; Valero L, C.; Banuelos F, A.; Hernandez D, V. M.; Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico); Paredes G, L., E-mail: fermineutron@yahoo.com [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2012-06-15

    The neutron spectrum and the absorbed dose in a Complementary Metal Oxide Semiconductor (CMOS), has been estimated using Monte Carlo methods. Eventually a person with a pacemaker becomes an oncology patient that must be treated in a linear accelerator. Pacemaker has integrated circuits as CMOS that are sensitive to intense and pulsed radiation fields. Above 7 MV therapeutic beam is contaminated with photoneutrons that could damage the CMOS. Here, the neutron spectrum and the absorbed dose in a CMOS cell was calculated, also the spectra were calculated in two point-like detectors in the room. Neutron spectrum in the CMOS cell shows a small peak between 0.1 to 1 MeV and a larger peak in the thermal region, joined by epithermal neutrons, same features were observed in the point-like detectors. The absorbed dose in the CMOS was 1.522 x 10{sup -17} Gy per neutron emitted by the source. (Author)

  18. Revisiting Warfarin Dosing Using Machine Learning Techniques

    Directory of Open Access Journals (Sweden)

    Ashkan Sharabiani

    2015-01-01

    Full Text Available Determining the appropriate dosage of warfarin is an important yet challenging task. Several prediction models have been proposed to estimate a therapeutic dose for patients. The models are either clinical models which contain clinical and demographic variables or pharmacogenetic models which additionally contain the genetic variables. In this paper, a new methodology for warfarin dosing is proposed. The patients are initially classified into two classes. The first class contains patients who require doses of >30 mg/wk and the second class contains patients who require doses of ≤30 mg/wk. This phase is performed using relevance vector machines. In the second phase, the optimal dose for each patient is predicted by two clinical regression models that are customized for each class of patients. The prediction accuracy of the model was 11.6 in terms of root mean squared error (RMSE and 8.4 in terms of mean absolute error (MAE. This was 15% and 5% lower than IWPC and Gage models (which are the most widely used models in practice, respectively, in terms of RMSE. In addition, the proposed model was compared with fixed-dose approach of 35 mg/wk, and the model proposed by Sharabiani et al. and its outperformance were proved in terms of both MAE and RMSE.

  19. Increase of Cisplatinum therapeutic index through optical irradiation

    Science.gov (United States)

    Fumarel, R.; Murgoi, Gabriela; Albert, P.; Hurduc, Anca; Pascu, M. L.

    2009-06-01

    The increase/modification of the Cisplatinum therapeutic index by neoplastic tissue exposure to optical radiation emitted between 400-2000 nm was studied; Cisplatinumum molecules do not absorb between 400 nm-2 □m. Doppler ultrasonography indicates that, following exposure, the living tissue local micro-vascularisation increases in a controlled and reversible way. The increase in the Cisplatinum therapeutic index may be produced by accelerating the intracellular hydrolyze processes due to the water molecules absorption in the near infrared. The irradiation makes possible the use of Cisplatinumum doses 10 times lower than in conventional chemotherapy; this generates lower secondary effects (kidney toxicity) while increasing the drug antineoplastic effect.

  20. CNS pharmacology and clinical therapeutic effects of oxiracetam.

    Science.gov (United States)

    Itil, T M; Menon, G N; Songar, A; Itil, K Z

    1986-01-01

    Oxiracetam, a new substance found to be a nootropic in experimental pharmacological studies, was tested in three clinical trials: a single rising dose tolerance and dose-finding study with quantitative pharmaco-electroencephalogram (pharmaco-EEG) and quantitative pharmacopsychology in healthy volunteers; a dose-finding study, at three dose levels for 3 months, with quantitative pharmaco-EEG in mild to moderate dementia patients; and a safety and efficacy study with increasing dosages for 12 weeks with subjective and objective tests in elderly patients with dementia. In single and repeated oral dosages up to 2,400 mg, oxiracetam is a safe compound. According to HZI Data Bank Classification Systems, oxiracetam is a vigilance-enhancing compound with some effects on spontaneous memory. The therapeutic effect of oxiracetam can be discriminated from placebo, and in comparison with piracetam, oxiracetam exhibits greater improvement in memory factor. PMID:3594458

  1. CNS pharmacology and clinical therapeutic effects of oxiracetam.

    Science.gov (United States)

    Itil, T M; Menon, G N; Songar, A; Itil, K Z

    1986-01-01

    Oxiracetam, a new substance found to be a nootropic in experimental pharmacological studies, was tested in three clinical trials: a single rising dose tolerance and dose-finding study with quantitative pharmaco-electroencephalogram (pharmaco-EEG) and quantitative pharmacopsychology in healthy volunteers; a dose-finding study, at three dose levels for 3 months, with quantitative pharmaco-EEG in mild to moderate dementia patients; and a safety and efficacy study with increasing dosages for 12 weeks with subjective and objective tests in elderly patients with dementia. In single and repeated oral dosages up to 2,400 mg, oxiracetam is a safe compound. According to HZI Data Bank Classification Systems, oxiracetam is a vigilance-enhancing compound with some effects on spontaneous memory. The therapeutic effect of oxiracetam can be discriminated from placebo, and in comparison with piracetam, oxiracetam exhibits greater improvement in memory factor.

  2. Registration of radiation doses

    International Nuclear Information System (INIS)

    In Finland the Radiation and Nuclear Safety Authority (STUK) is maintaining the register (called Dose Register) of the radiation exposure of occupationally exposed workers in order to ensure compliance with the principles of optimisation and individual protection. The guide contains a description of the Dose Register and specifies the responsibilities of the party running a radiation practice to report the relevant information to the Dose Register

  3. Therapeutics in Huntington's Disease.

    Science.gov (United States)

    Killoran, Annie; Biglan, Kevin M

    2012-02-01

    OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there

  4. Bacteriophage Procurement for Therapeutic Purposes.

    Science.gov (United States)

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  5. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed. PMID:20930555

  6. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  7. Clinical applications of therapeutic phlebotomy

    Directory of Open Access Journals (Sweden)

    Kim KH

    2016-07-01

    Full Text Available Kyung Hee Kim,1 Ki Young Oh,2 1Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, 2Department of Physical Medicine and Rehabilitation, Soonchunhyang University, Cheonan Hospital, Cheonan, South Korea Abstract: Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. Keywords: therapeutic phlebotomy, hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, nonalcoholic fatty liver disease

  8. Psychotropic effects of aspirin, acetylsalicylate cobalt and acetylsalicylate zinc at various doses

    OpenAIRE

    Tatyana V. Yakovchyuk; Oksana V. Katiushyna; Ivan I. Koreniuk; Denis R. Khusainov; Tatyana V. Gamma

    2012-01-01

    For the first time it is shown that psychotropic action of acetylsalicylates at various doses is manifested as a nonmonotonic dependence having its peaks at therapeutic and ultra-low dose zones. It is discovered that development of effects of aspirin resembles that of acetylsalicylate zinc. Acetylsalicylate cobalt at extremely low doses zone showed the highest antidepressant activity, demonstrating toxicity at high doses. Generally, it is revealed that the use of aspirin and its salts at high...

  9. Dose-dense Temozolomide: Is It Still Promising?

    OpenAIRE

    Nagane, Motoo

    2014-01-01

    Glioblastoma (GBM) has proven to be incurable despite recent progress on its standard of care using temozolomide (TMZ) as the main trunk of initial therapy for newly diagnosed GBM. One of the main reasons accounting for the dismal prognosis is attributed to lack of active therapeutic regimens at recurrence. Since TMZ is the most active cytotoxic agent against GBM, and the standard dosing of TMZ has shown favorable safety profile in clinical trials, re-challenge with TMZ in increased dose dens...

  10. Therapeutic Potential of Human Neutrophil Peptide 1 against Experimental Tuberculosis

    OpenAIRE

    Sharma, Sudhir; Verma, Indu; Khuller, G. K.

    2001-01-01

    The therapeutic efficacy of human neutrophil peptide 1 (HNP-1) against experimental tuberculosis in mice on the basis of numbers of CFU has been examined. Mice infected with 1.5 × 104 CFU of Mycobacterium tuberculosis H37Rv and treated with different doses of HNP-1 injected subcutaneously exhibited significant clearance of bacilli from lungs, livers, and spleens. There were time- and dose-dependent decreases in the bacillary load in lungs, livers, and spleens of the HNP-1-treated animals comp...

  11. Radiosensitizers action on Iodine 131 therapeutical effect

    International Nuclear Information System (INIS)

    Present studies were aimed to research the possible application of a radiosensitizer, nicotinamide, to increase the therapeutical effect of radioiodine. There were used goitrous and normal rats with growing dose of Iodine 131, with and without simultaneous treatment with nicotinamide. The obtained results show that the nicotinamide treatment importantly increases the thyroid radio destructive effect induced by radioiodine. Under these experimental conditions, nicotinamide induces to a significant increase of thyroid vascularisation, without changes in the proteins ADP-ribosylation activity. These results show, for the first time, the radiosensitizer effect of nicotinamide in front of Iodine 131 and give the possibility of using it in the treatment of hyperthyroid or thyroid difference cancer patients. (author)

  12. Critical metal blistering doses

    Energy Technology Data Exchange (ETDEWEB)

    Kalin, B.A.; Kirilin, N.M.; Pisarev, A.A.

    1975-08-01

    Critical He ion bombardment doses associated with blistering of Nb and stainless steel were measured. It was found that the critical doses for these materials are close together and in the range 1 to 4 x 10/sup 17/ ion/cm/sup 2/. (JRD)

  13. HOW RELIABLE IS 24 HOUR SERUM LITHIUM LEVEL AFTER A TEST DOSE OF LITHIUM IN PREDICTING OPTIMAL LITHIUM DOSE?

    OpenAIRE

    Kuruvilla, K.; Shaji, K. S.

    1989-01-01

    SUMMARY 57% of a group of 35 patients treated with Lithium Carbonate at dosages predicted by the nomogram suggested by Cooper et al (1973) failed to reach therapeutic levels of serum lithium. This finding casts serious doubts on the usefulness of the claim by Cooper et al (1973 & 1976) that 24 hour serum lithium level after a test dose of 600 mg. lithium can predict the daily lithium dose.

  14. Radiopharmaceuticals as therapeutic agents in medical care and treatment

    International Nuclear Information System (INIS)

    Radiation applications in medical research, care, and treatment today are being used to help millions of patients throughout the world. In recent years, the medical community has seen a renaissance of therapeutic radiation applications, particularly of strontium-89 for metastatic bone pain. Radiopharmaceuticals used as therapeutic agents (frequently known as RPTs) are designed to deliver high doses of radiation to selected malignant sites in target organs or tissues, while minimizing the radiation doses to surrounding healthy cells. Over the past several years, several type of RPTs with special properties, including compounds for labelling monoclonal antibodies, have been used in animal and human clinical trials with promising results. The modern trend in radiopharmaceutical research for oncology is the development of RPTs that may be said to be tumour-seeking and tumour-specific. Among the promising RPTs being reported in the medical literature are rhenium-186 and samarium-153. Both can be produced in research reactors available in many countries. 2 tabs

  15. Therapeutic Applications of Monte Carlo Calculations in Nuclear Medicine

    CERN Document Server

    Sgouros, George

    2003-01-01

    This book examines the applications of Monte Carlo (MC) calculations in therapeutic nuclear medicine, from basic principles to computer implementations of software packages and their applications in radiation dosimetry and treatment planning. It is written for nuclear medicine physicists and physicians as well as radiation oncologists, and can serve as a supplementary text for medical imaging, radiation dosimetry and nuclear engineering graduate courses in science, medical and engineering faculties. With chapters is written by recognised authorities in that particular field, the book covers the entire range of MC applications in therapeutic medical and health physics, from its use in imaging prior to therapy to dose distribution modelling targeted radiotherapy. The contributions discuss the fundamental concepts of radiation dosimetry, radiobiological aspects of targeted radionuclide therapy and the various components and steps required for implementing a dose calculation and treatment planning methodology in ...

  16. Dose response relationship at low doses

    International Nuclear Information System (INIS)

    The data that have accrued in Hiroshima and Nagasaki on the effects of ionizing radiation on the developing human brain are reviewed. Effects considered are severe mental retardation, lowered IQ scores, decline in school performance, seizures, other neuropsychological effects, and small head size. All these factors may be related to radiation doses received by the mother during pregnancy. (L.L.) 3 figs., tab., 7 refs

  17. Mechanisms and therapeutic effectiveness of lactobacilli.

    Science.gov (United States)

    Di Cerbo, Alessandro; Palmieri, Beniamino; Aponte, Maria; Morales-Medina, Julio Cesar; Iannitti, Tommaso

    2016-03-01

    The gut microbiome is not a silent ecosystem but exerts several physiological and immunological functions. For many decades, lactobacilli have been used as an effective therapy for treatment of several pathological conditions displaying an overall positive safety profile. This review summarises the mechanisms and clinical evidence supporting therapeutic efficacy of lactobacilli. We searched Pubmed/Medline using the keyword 'Lactobacillus'. Selected papers from 1950 to 2015 were chosen on the basis of their content. Relevant clinical and experimental articles using lactobacilli as therapeutic agents have been included. Applications of lactobacilli include kidney support for renal insufficiency, pancreas health, management of metabolic imbalance, and cancer treatment and prevention. In vitro and in vivo investigations have shown that prolonged lactobacilli administration induces qualitative and quantitative modifications in the human gastrointestinal microbial ecosystem with encouraging perspectives in counteracting pathology-associated physiological and immunological changes. Few studies have highlighted the risk of translocation with subsequent sepsis and bacteraemia following probiotic administration but there is still a lack of investigations on the dose effect of these compounds. Great care is thus required in the choice of the proper Lactobacillus species, their genetic stability and the translocation risk, mainly related to inflammatory disease-induced gut mucosa enhanced permeability. Finally, we need to determine the adequate amount of bacteria to be delivered in order to achieve the best clinical efficacy decreasing the risk of side effects.

  18. [The therapeutic problem of current drug addiction in Italy].

    Science.gov (United States)

    De Caro, D

    1980-04-28

    Psicosocial factors which are of main importance for drug-dependences, especially in young people, are examined. Then the most important elements of the therapy of drug-dependences are indicated, which first of all consists in the necessary treatment in the hospital and farmacological therapy (particularly during acute and over-dose states), and also psicotherapeutic--generally speaking--and social approaches. Among those therapeutic Communities seem to be extremely significant, whose most important patterns are described.

  19. Artemether-lumefantrine nanostructured lipid carriers for oral malaria therapy: Enhanced efficacy at reduced dose and dosing frequency.

    Science.gov (United States)

    Prabhu, Priyanka; Suryavanshi, Shital; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

    2016-09-10

    Artemether-lumefantrine (ARM-LFN) is a World Health Organization (WHO) approved fixed-dose combination having low solubility and poor oral bioavailability. Nanostructured lipid carriers (NLC) were developed to enhance the oral efficacy of this combination using the microemulsion template technique. They were characterized for drug content, entrapment efficiency, size distribution, in vitro release, antimalarial efficacy, and toxicity. The NLC showed sustained drug release. The recommended adult therapeutic dose is 80mg ARM and 480mg LFN (4 tablets) twice a day, which amounts to 160mg ARM and 960mg LFN daily. ARM-LFN NLC given once a day at 1/5 of therapeutic dose (16mg ARM and 96mg LFN) showed complete parasite clearance and 100% survival in Plasmodium berghei-infected mice. 33% of the mice treated with marketed tablets twice a day at the therapeutic dose showed late-stage recrudescence. Thus, NLC showed enhanced efficacy at 1/10 of the daily dose of ARM-LFN. The 10-fold reduced daily dose was formulated in two soft gelatin capsules thus reducing the number of units to be taken at a time by the patient. The capsules showed good stability at room temperature for a year. The NLC were found to be safe in rats. The biocompatible NLC developed using an industrially feasible technique offer a promising solution for oral malaria therapy. PMID:27421912

  20. Evidence Based Digoxin Therapeutic Monitoring - A Lower and Narrower Therapeutic Range

    Directory of Open Access Journals (Sweden)

    Amine BENLMOUDEN

    2016-06-01

    Full Text Available Cardiac glycosides have been used for congestive heart failure and certain cardiac arrhythmias for more than 200 years. Despite the introduction of a variety of new classes of drugs for the management of heart failure, specifically angiotensin-converting enzyme (ACE inhibitors, b-adrenergic antagonists (bblockers, and the aldosterone antagonist spironolactone, digoxin continues to have an important role in long-term outpatient management. However, a narrow margin exists between therapeutic and toxic doses of digoxin, resulting in a high incidence of digoxin toxicity in clinical practice.A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. The clinical relevance of digoxin therapeutic monitoring is also proved but the SDC (Serum Digoxin Conentrations required for optimal clinical efficacy and acceptable toxicity remains controversial. In the last years, international guidelines recommend 1.2 ng/mL as acceptable high level.In this bibliographic synthesis, we aim to collect pertinent informations from MedLine database about exposure-effect relationship in order to assess the evidence level scientific of new digoxin therapeutic monitoring. 

  1. BNCT and dose fractionation

    International Nuclear Information System (INIS)

    Some portion of the radiation dose received by a patient during BNCT consists of primary and secondary gammas. The biological effect of that portion of the dose will depend upon the time history of the delivered dose. The well-known models for relating time-dose effects to clinical experience, are of questionable value in understanding dose effects in the time regime of a few hours, and for doses of less than tolerance. In order to examine the time-dose effect in the regime of interest to BNCT a simple phenomenological model was developed and normalized to the accepted body of clinical experience. The model has been applied to the question of fractionation of BNCT and the results are presented. The model is simply a linear healing model with two time constants. In other words, a first hit of radiation is assumed to wound (or potentiate) a cell. Given time, the cell will fully repair itself. If a second hit occurs before the cell has healed, the cell is killed. Apparently, there are two kinds of healing, one which occurs in 30 to 60 minutes, the other in two to four days. A small fraction of the cells will die on the first hit

  2. Potential therapeutic uses of mecamylamine and its stereoisomers.

    Science.gov (United States)

    Nickell, Justin R; Grinevich, Vladimir P; Siripurapu, Kiran B; Smith, Andrew M; Dwoskin, Linda P

    2013-07-01

    Mecamylamine (3-methylaminoisocamphane hydrochloride) is a nicotinic parasympathetic ganglionic blocker, originally utilized as a therapeutic agent to treat hypertension. Mecamylamine administration produces several deleterious side effects at therapeutically relevant doses. As such, mecamylamine's use as an antihypertensive agent was phased out, except in severe hypertension. Mecamylamine easily traverses the blood-brain barrier to reach the central nervous system (CNS), where it acts as a nicotinic acetylcholine receptor (nAChR) antagonist, inhibiting all known nAChR subtypes. Since nAChRs play a major role in numerous physiological and pathological processes, it is not surprising that mecamylamine has been evaluated for its potential therapeutic effects in a wide variety of CNS disorders, including addiction. Importantly, mecamylamine produces its therapeutic effects on the CNS at doses 3-fold lower than those used to treat hypertension, which diminishes the probability of peripheral side effects. This review focuses on the pharmacological properties of mecamylamine, the differential effects of its stereoisomers, S(+)- and R(-)-mecamylamine, and the potential for effectiveness in treating CNS disorders, including nicotine and alcohol addiction, mood disorders, cognitive impairment and attention deficit hyperactivity disorder.

  3. How to Use Equipment Therapeutically.

    Science.gov (United States)

    Bowne, Douglas

    1986-01-01

    Shares therapeutic and economic practices surrounding equipment used in New York's Higher Horizons adventure program of therapy for troubled youth. Encourages educators, therapists, and administrators to explore relationship between equipment selection, program goals, and clients. (NEC)

  4. Attachment theory and therapeutic relationships

    OpenAIRE

    Boysan, Zehra

    2015-01-01

    The aims of this study were to examine the associations between current self-reported attachment styles, retrospective reports of childhood experiences, and the development of the therapeutic alliance. It was hypothesised that anxious and avoidant attachment would be correlated with negative childhood experiences and that both attachment anxiety and avoidance would be inversely correlated with the therapeutic alliance. The third hypothesis stated that negative childhood recollections would co...

  5. [Therapeutic touch and anorexia nervosa].

    Science.gov (United States)

    Satori, Nadine

    2016-01-01

    An innovative practice, therapeutic touch has been used for around ten years in the treatment of eating disorders. Delivered by nurse clinicians having received specific training, this approach is based on nursing diagnoses which identify the major symptoms of this pathology. The support is built around the body and its perceptions. Through the helping relationship, it mobilises the patient's resources to favour a relationship of trust, a letting-go, physical, psychological and emotional relaxation, and improves the therapeutic alliance. PMID:27615696

  6. Metrics for antibody therapeutics development

    OpenAIRE

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approv...

  7. Therapeutic cloning: promises and issues

    OpenAIRE

    Kfoury, Charlotte

    2007-01-01

    Advances in biotechnology necessitate both an understanding of scientific principles and ethical implications to be clinically applicable in medicine. In this regard, therapeutic cloning offers significant potential in regenerative medicine by circumventing immunorejection, and in the cure of genetic disorders when used in conjunction with gene therapy. Therapeutic cloning in the context of cell replacement therapy holds a huge potential for de novo organogenesis and the permanent treatment o...

  8. Therapeutic Vaccines for Chronic Infections

    Science.gov (United States)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

  9. Microdosimetry of high LET therapeutic beams

    International Nuclear Information System (INIS)

    Experimental microdosimetry of high LET therapeutic beams were presented. The cyclotron produced fast neutron beams at IMS, TAMVEC and NRL, a reactor fast neutron at YAYOI, a proctor beam at Harvard and a pion beam at TRIUMF are included. Measurements were performed with a conventional tissue equivalent spherical proportional counter with a logarithmic amplifier which made the recording and analysis quite simple. All the energy deposition spectra were analysed in the conventional manner and anti y F, anti y D as well as anti y D* were calculated. The spectra and their mean lineal energies showed wide variations, depending on the particle type, energy, position in phantom. Fractional contribution of elemental particles ( electron, muon, pion, proton, alpha and so on) to the total dose were analysed. For fast neutron beams, the y spectra stayed almost constant at any depth along the central axis in the phantom. The y spectra of proton beam changed slightly along the depth. On the other side, the y spectra of pion beam change drastically in the phantom between plateau and dose peak region. A novel technique of time-of-flight microdosimetry was employed, which made it possible to separate the fractional contribution of contaminant electrons and muons out of pions. Finally, a map of the radiation quality for all the beams is presented and its significances are discussed. (author)

  10. Frequency and collective effective dose equivalent of medical exposures

    International Nuclear Information System (INIS)

    According to ICRP recommendation, medical exposure refers to the intentional exposure of patients for diagnostic and therapeutic purposes, and to the exposures resulting from the artificial replacement of body organs or functions. Since the objective of radiotherapy is to give a large amount of radiation dose to the patient to kill cancer cells, neither individual nor collective effective doses are directly relevant for comparisons with doses from other sources, not even with diagnostic procedures. For this reason, in present report, therapeutic uses of radiations and radiopharmaceuticals are not included in the medical exposures. Medical exposures in Japan have been investigated by the nationwide surveys on the type and the frequency of radiological procedures and by the dose determinations with phantom experiments or calculations since 1960. Present report reviews the frequency of diagnostic radiological procedures and the collective effective dose equivalents from these procedures, and excess deaths from the medical exposures in Japan. In 1986, the number of X-ray diagnostic examinations was estimated to be about 1.41 x 108. The preliminary result in 1991 shows the number will be about 1.8 x 108. The resultant collective effective dose equivalent from X-ray diagnosis in 1986 was about 1.84 x 105 person Sv. Consequently per Caput mean effective dose equivalent was about 1.48 mSv/person in 1986. The total collective effective dose equivalent from all the diagnostic radiological procedures in Japan was estimated to be about 2.96 x 105 person Sv/year. per Caput mean effective dose equivalent from the total diagnostic radiological procedures in Japan was evaluated to be about 2.3 mSv/year. This value may be comparable to the mean annual effective dose equivalent received from natural radiations for the worldwide population. Mean effective dose equivalent per diagnostic radiological examination was calculated to be about 1.00 mSv/examination. (author)

  11. O ultra-som terapêutico de 1 MHz, na dose de 0,5 W cm-2, sobre o tecido ósseo de cães avaliado por densitometria óptica em imagens radiográficas The 1 MHz therapeutic ultrasound, in doses of 0.5W cm-2, on dog's bone tissue evaluated through optic densitometry in radiographic images

    Directory of Open Access Journals (Sweden)

    Douglas Severo Silveira

    2008-11-01

    Full Text Available As lesões tendíneas nas extremidades distais dos membros estão entre as mais freqüentes alterações do aparelho locomotor na rotina clínico-cirúrgica humana e animal e, não raro, necessitam de terapias adjuvantes para seu completo retorno às funções fisiológicas. O ultra-som terapêutico (UST é a modalidade mais utilizada nas clínicas de reabilitação para tratar lesões tendíneas, mas devido à falta ou a divergências de estudos específicos sobre seus efeitos no tecido ósseo, sua utilização sobre as regiões distais dos membros, ricas em protuberâncias ósseas e áreas desprovidas de cobertura muscular, sempre preocuparam os profissionais da área médica. No intuito de esclarecer os efeitos do UST sobre o tecido ósseo, seis cães receberam tratamento ultra-sônico contínuo, de 1MHz, durante cinco minutos diários, por um período de 20 dias sobre a região craniodistal do rádio e da ulna. A intensidade do UST aplicada foi de 0,5W cm-2 no membro torácico direito, ficando o membro contralateral como controle. A região distal de ambos os membros torácicos foi radiografada para análise de densitometria óssea em imagens radiográficas, antes do início da terapia e ao final do tratamento. Não houve alterações significativas de densidade mineral óssea entre os membros tratados e os controles. Conclui-se que dentro dos parâmetros utilizados no experimento a utilização do UST em regiões ósseas protuberantes ou desprovidas de cobertura muscular pode ser feita com segurança.Tendon lesions on distal extremities of the limbs are among the most frequent alterations of the locomotor system in the human and animal clinic-surgery routine, and frequently need supplementary therapy for the complete recovery of the physiologic functions. The therapeutic ultrasound (TUS is the mostly used apparatus in rehabilitation clinics to treat tendon lesions, but due to the lack or the divergence on specific studies about its effects

  12. Radiation dose in vertebroplasty

    Energy Technology Data Exchange (ETDEWEB)

    Mehdizade, A.; Lovblad, K.O.; Wilhelm, K.E.; Somon, T.; Wetzel, S.G.; Kelekis, A.D.; Yilmaz, H.; Abdo, G.; Martin, J.B.; Viera, J.M.; Ruefenacht, D.A. [Neuroradiology DRRI, Geneva University Hospital, Rue Micheli-du-Crest 24, 1211, Geneva 14 (Switzerland)

    2004-03-01

    We wished to measure the absorbed radiation dose during fluoroscopically controlled vertebroplasty and to assess the possibility of deterministic radiation effects to the operator. The dose was measured in 11 consecutive procedures using thermoluminescent ring dosimeters on the hand of the operator and electronic dosimeters inside and outside of the operator's lead apron. We found doses of 0.022-3.256 mGy outside and 0.01-0.47 mGy inside the lead apron. Doses on the hand were higher, 0.5-8.5 mGy. This preliminary study indicates greater exposure to the operator's hands than expected from traditional apron measurements. (orig.)

  13. Controllable dose; Dosis controlable

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, J.T.; Anaya M, R.A. [ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico)]. E-mail: jtar@nuclear.inin.mx

    2004-07-01

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  14. Gonadal doses from radiotherapy

    International Nuclear Information System (INIS)

    The method of calculation of gonadal doses arising from different radiotherapeutic procedures is described. The measurement of scatter factors to the gonads from superficial and deep therapy is detailed and the analytic fits to the experimental data, as a function of field position, field size and beam energy are given. The data used to calculate the gonadal doses from treatments using linear accelerators, teletherapy and sealed sources are described and the analytic fits to the data given

  15. Effects of low doses

    International Nuclear Information System (INIS)

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  16. Prostate cancer: Doses and volumes of radiotherapy; Cancer de prostate: doses et volumes cibles

    Energy Technology Data Exchange (ETDEWEB)

    Hennequin, C.; Rivera, S.; Quero, L. [Service de cancerologie-radiotherapie, hopital Saint-Louis, AP-HP, 75 - Paris (France); Latorzeff, I. [Service de radiotherapie, groupe Oncorad-Garonne, clinique Pasteur, -l' Atrium-, 31 - Toulouse (France)

    2010-10-15

    Radiotherapy is nowadays a major therapeutic option in prostate cancer. Technological improvements allowed dose escalation without increasing late toxicity. Some randomized trials have shown that dose escalation decreases the biochemical failure rate, without any benefit in survival with the present follow-up. However, some studies indicate that the distant metastases rate is also decreased. Most of these studies have been done without hormonal treatment, and the role of dose escalation in case of long-term androgen deprivation is unknown. The target volume encompassed the whole gland: however, complete or partial focal treatment of the prostate can be done with sophisticated IMRT technique and must be evaluated. Proximal part of the seminal vesicles must be included in the target volumes. The role of nodal irradiation is another debate, but it could be logically proposed for the unfavourable group. (authors)

  17. Assessment of organ equivalent doses and effective doses from diagnostic X-ray examinations

    International Nuclear Information System (INIS)

    The MIRD-type adult male, female and age 10 phantoms were constructed to evaluate organ equivalent dose and effective dose of patient due to typical diagnostic X-ray examination. These phantoms were constructed with external and internal dimensions of Korean. The X-ray energy spectra were generated with SPEC78. MCNP4B ,the general-purposed Monte Carlo code, was used. Information of chest PA , chest LAT, and abdomen AP diagnostic X-ray procedures was collected on the protocol of domestic hospitals. The results showed that patients pick up approximate 0.02 to 0.18 mSv of effective dose from a single chest PA examination, and 0.01 to 0.19 mSv from a chest LAT examination depending on the ages. From an abdomen AP examination, patients pick up 0.17 to 1.40 mSv of effective dose. Exposure time, organ depth from the entrance surface and X-ray beam field coverage considerably affect the resulting doses. Deviation among medical institutions is somewhat high, and this indicated that medical institutions should interchange their information and the need of education for medical staff. The methodology and the established system can be applied, with some expansion, to dose assessment for other medical procedures accompanying radiation exposure of patients like nuclear medicine or therapeutic radiology

  18. Radiation dosimetry in developing a radioactive stent for therapeutic use

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Hee; Kim, Jang Hee; Chung, Wee Sup; Woo, Kwang Sun [Korea Cancer Center Hospital , Seoul (Korea, Republic of)

    1997-09-01

    Research Goal: A new radioation therapy protocol of the esophageal carcinoma has been proposed. A metal stent coated with beta-emitting radioisotope would be inserted into the lesion of malignant esophageal obstruction and irradiate it. In this study, dose to the esophageal wall is estimated to suggest the selection of radioisotope, total activity, and the activity distribution pattern over the stent. Result: Dose distribution of the esophageal wall is determined by the energy spectrum of beta particles emitted from the radioisotope used in the stent activation. The endpoint energy of the beta spectrum corresponds to a range in liquid water, which determines the depth into the esophageal wall where the dose is significant. With a stent of constant areal activity density, dose to the esophageal wall increases with an increasing stent height until reaching a saturation value. Dose is maximum at the esophageal wall surface. The degree of dose decreasing as the target moves into the esophageal wall varies among different radioisotopes. However, dose decreases by similar degree among different radioisotopes as the target moves from the stent central height toward the stent end. For a stent of 2 cm in diameter, more than 4 cm in heigh, and 10 {mu}Ci/cm{sup 2} in activity, dose at the esophageal wall surface and at the stent central height is {approx}70 Gy, {approx}60 Gy, {approx}50 Gy, {approx}50 Gy, {approx}25 Gy, and {approx}15 Gy for {sup 90}Y, {sup 188}Re, {sup 166}Ho, {sup 32}P, {sup 186}Re, and {sup 192}Ir, respectively. Applications: Dose estimates provided in this study and the experimental results from the researchers at Yonsei University, who applied the radioactive stent to animals, will be used to analyze the relationship between the stent design and the corresponding therapeutic effect. This helps utilizing the new protocol of treating the esophageal carcinoma. 37 refs., 18 tabs., 27 figs. (author)

  19. Individualized dose prescription for hypofractionation in advanced non-small-cell lung cancer radiotherapy: an in silico trial.

    NARCIS (Netherlands)

    Hoffmann, A.L.; Troost, E.G.C.; Huizenga, H.; Kaanders, J.H.A.M.; Bussink, J.

    2012-01-01

    PURPOSE: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various h

  20. Confusion: acetaminophen dosing changes based on NO evidence in adults.

    Science.gov (United States)

    Krenzelok, Edward P; Royal, Mike A

    2012-06-01

    Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used? PMID:22530736

  1. Individualized Dose Prescription for Hypofractionation in Advanced Non-Small-Cell Lung Cancer Radiotherapy: An in silico Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Bussink, Johan, E-mail: j.bussink@rther.umcn.nl [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands)

    2012-08-01

    Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose

  2. Utirik Atoll Dose Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Robison, W.L.; Conrado, C.L.; Bogen, K.T

    1999-10-06

    On March 1, 1954, radioactive fallout from the nuclear test at Bikini Atoll code-named BRAVO was deposited on Utirik Atoll which lies about 187 km (300 miles) east of Bikini Atoll. The residents of Utirik were evacuated three days after the fallout started and returned to their atoll in May 1954. In this report we provide a final dose assessment for current conditions at the atoll based on extensive data generated from samples collected in 1993 and 1994. The estimated population average maximum annual effective dose using a diet including imported foods is 0.037 mSv y{sup -1} (3.7 mrem y{sup -1}). The 95% confidence limits are within a factor of three of their population average value. The population average integrated effective dose over 30-, 50-, and 70-y is 0.84 mSv (84, mrem), 1.2 mSv (120 mrem), and 1.4 mSv (140 mrem), respectively. The 95% confidence limits on the population-average value post 1998, i.e., the 30-, 50-, and 70-y integral doses, are within a factor of two of the mean value and are independent of time, t, for t > 5 y. Cesium-137 ({sup 137}Cs) is the radionuclide that contributes most of this dose, mostly through the terrestrial food chain and secondarily from external gamma exposure. The dose from weapons-related radionuclides is very low and of no consequence to the health of the population. The annual background doses in the U. S. and Europe are 3.0 mSv (300 mrem), and 2.4 mSv (240 mrem), respectively. The annual background dose in the Marshall Islands is estimated to be 1.4 mSv (140 mrem). The total estimated combined Marshall Islands background dose plus the weapons-related dose is about 1.5 mSv y{sup -1} (150 mrem y{sup -1}) which can be directly compared to the annual background effective dose of 3.0 mSv y{sup -1} (300 mrem y{sup -1}) for the U. S. and 2.4 mSv y{sup -1} (240 mrem y{sup -1}) for Europe. Moreover, the doses listed in this report are based only on the radiological decay of {sup 137}Cs (30.1 y half-life) and other

  3. Bone-seeking therapeutic radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Srivastava Suresh C.

    2002-01-01

    Full Text Available Bone-seeking therapeutic radiopharmaceuticals are utilized on the basis of the radionuclide?s particulate emissions (primarily low to intermediate beta emission. The requirements therefore are different from those of bone imaging agents that consist mainly of short-lived single photon emitters. Lately, the therapeutic bone seeking radiopharmaceuticals have attained increasing importance due to their potential role in alleviating pain from osseous metastases in cancer patients, for the treatment of joint pain resulting from inflamed synovium (radiosynoviorthesis, or radiosynovectomy, or from various other forms of arthritic disease. There is, however, a paucity of published data on the bio-pharmacokinetics of these agents when used following intravenous administration for bone pain palliation. This paper will briefly review and summarize the presently available chemical and biopharmacokinetic information on the various clinically approved as well as experimental bone-localizing therapeutic radiopharmaceuticals, and make projections on their clinical application for the treatment of primary/metastatic cancer in bone.

  4. Conflicts in the therapeutic field

    Directory of Open Access Journals (Sweden)

    Antonino Aprea

    2012-06-01

    Full Text Available How the analytical knowledge that compare human consciousness with that, even more disturbing, moving behind his fifth can be said to be “for peace”? It can be - and this will be the contribution of the proposal - the same tortuous and enigmatic of therapeutic practice, with its hesitations and his impulses, to outline a path crossing and overcoming the conflict? May, finally, peace, in the sense of feasibility of intra-and interpersonal dialectic instead of tearing and hostileconfrontation with oneself and with the other, to be a reference in some crucial pivot of ethical therapeutic work? To these questions the intervention seeks to answer retracing some of the highlights of almost three years of therapeutic work with a young woman and her family.

  5. Therapeutic hypothermia for acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

    2003-01-01

    Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... is directly related to stroke severity and outcome, and fever after stroke is associated with substantial increases in morbidity and mortality. Normalisation of temperature in acute stroke by antipyretics is generally recommended, although there is no direct evidence to support this treatment. Despite its...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

  6. Who needs a therapeutic phlebotomy?

    Science.gov (United States)

    Antle, Emily Amy

    2010-12-01

    Many oncology practices treat patients with benign and malignant hematologic diagnoses. As a result, oncology nurses often are required to care for these patients. One common procedure nurses perform is therapeutic phlebotomy, where about 500 ml of blood is removed through a large-bore needle over 15-30 minutes. The procedure is ordered as a treatment for hereditary hemochromatosis, polycythemia vera, and secondary polycythemia. Before initiating the procedure, nurses must be aware of a patient's diagnosis, baseline hemoglobin, hematocrit, ferritin, and therapeutic end points. Reviewing these diagnoses will help nurses understand why phlebotomy is an important part of treatment.

  7. Assessment of internal doses

    CERN Document Server

    Rahola, T; Falk, R; Isaksson, M; Skuterud, L

    2002-01-01

    There is a definite need for training in dose calculation. Our first course was successful and was followed by a second, both courses were fully booked. An example of new tools for software products for bioassay analysis and internal dose assessment is the Integrated Modules for Bioassay Analysis (IMBA) were demonstrated at the second course. This suite of quality assured code modules have been adopted in the UK as the standard for regulatory assessment purposes. The intercomparison measurements are an important part of the Quality Assurance work. In what is known as the sup O utside workers ' directive it is stated that the internal dose measurements shall be included in the European Unions supervision system for radiation protection. The emergency preparedness regarding internal contamination was much improved by the training with and calibration of handheld instruments from participants' laboratories. More improvement will be gained with the handbook giving practical instructions on what to do in case of e...

  8. Prasugrel or double-dose clopidogrel to overcome clopidogrel low-response

    DEFF Research Database (Denmark)

    Dridi, Nadia Paarup; Johansson, Pär Ingemar; Clemmensen, Peter;

    2014-01-01

    antiplatelet regimen: 52 were assigned to double maintenance-dose clopidogrel and 54 to standard-dose prasugrel. At 1 month, tailoring antiplatelet therapy improved platelet inhibition to a level considered as therapeutic in 73.1% of patients. Prasugrel entailed greater platelet inhibition (p = 0...

  9. Dose Reduction Techniques

    International Nuclear Information System (INIS)

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program

  10. Radioactive cloud dose calculations

    International Nuclear Information System (INIS)

    Radiological dosage principles, as well as methods for calculating external and internal dose rates, following dispersion and deposition of radioactive materials in the atmosphere are described. Emphasis has been placed on analytical solutions that are appropriate for hand calculations. In addition, the methods for calculating dose rates from ingestion are discussed. A brief description of several computer programs are included for information on radionuclides. There has been no attempt to be comprehensive, and only a sampling of programs has been selected to illustrate the variety available

  11. Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques

    OpenAIRE

    Henning, Lisa N.; Comer, Jason E.; Stark, Gregory V.; Ray, Bryan D.; Tordoff, Kevin P.; Knostman, Katherine A. B.; Meister, Gabriel T.

    2012-01-01

    Appropriate animal models are required to test medical countermeasures to bioterrorist threats. To that end, we characterized a nonhuman primate (NHP) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the U.S. Food and Drug Administration Animal Rule. A clinical profile was recorded for each NHP exposed to a lethal dose of Bacillus anthracis Ames spores. Specific diagnostic parameters were detected relatively early in disease pr...

  12. Real-time, aptamer-based tracking of circulating therapeutic agents in living animals

    OpenAIRE

    Ferguson, B. Scott; Hoggarth, David A.; Maliniak, Dan; Ploense, Kyle; White, Ryan J.; Woodward, Nick; Hsieh, Kuangwen; Bonham, Andrew J.; Eisenstein, Michael; Kippin, Tod; Plaxco, Kevin W.; Soh, H. Tom

    2013-01-01

    A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients’ health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lact...

  13. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of 131I in Hyperthyroidism

    OpenAIRE

    Kartamihardja, A. Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had b...

  14. Therapeutic efficacy of natural prostaglandin in the treatment of pyometra in bitches

    OpenAIRE

    Basanti Jena; K. Sadasiva Rao; K. C. S. Reddy; K. B. P. Raghavender

    2013-01-01

    Aim: The current study was done to study the therapeutic effect of natural prostaglandin in treatment of canine pyometra. Materials and Methods: Seven bitches were treated with natural PGF2 á i.e. dinoprost tromethamine at the dose rate of 100 μg/kg body weight subcutaneously once daily for 7 days with supportive therapies. The physiological, haematological and biochemical parameters were studied before (0th day) and after treatment (8th day). Therapeutic efficacy was assessed in te...

  15. Dose calculation from a D-D-reaction-based BSA for boron neutron capture synovectomy

    International Nuclear Information System (INIS)

    Monte Carlo simulations were carried out to calculate dose in a knee phantom from a D-D-reaction-based Beam Shaping Assembly (BSA) for Boron Neutron Capture Synovectomy (BNCS). The BSA consists of a D(d,n)-reaction-based neutron source enclosed inside a polyethylene moderator and graphite reflector. The polyethylene moderator and graphite reflector sizes were optimized to deliver the highest ratio of thermal to fast neutron yield at the knee phantom. Then neutron dose was calculated at various depths in a knee phantom loaded with boron and therapeutic ratios of synovium dose/skin dose and synovium dose/bone dose were determined. Normalized to same boron loading in synovium, the values of the therapeutic ratios obtained in the present study are 12-30 times higher than the published values.

  16. Dose calculation from a D-D-reaction-based BSA for boron neutron capture synovectomy

    Energy Technology Data Exchange (ETDEWEB)

    Abdalla, Khalid [Department of Physics, Hail University, Hail (Saudi Arabia)], E-mail: khalidafnan@uoh.edu.sa; Naqvi, A.A. [Department of Physics, King Fahd University of Petroleum and Minerals and Center for Applied Physical Sciences, Box No. 1815, Dhahran 31261 (Saudi Arabia)], E-mail: aanaqvi@kfupm.edu.sa; Maalej, N.; Elshahat, B. [Department of Physics, King Fahd University of Petroleum and Minerals and Center for Applied Physical Sciences, Box No. 1815, Dhahran 31261 (Saudi Arabia)

    2010-04-15

    Monte Carlo simulations were carried out to calculate dose in a knee phantom from a D-D-reaction-based Beam Shaping Assembly (BSA) for Boron Neutron Capture Synovectomy (BNCS). The BSA consists of a D(d,n)-reaction-based neutron source enclosed inside a polyethylene moderator and graphite reflector. The polyethylene moderator and graphite reflector sizes were optimized to deliver the highest ratio of thermal to fast neutron yield at the knee phantom. Then neutron dose was calculated at various depths in a knee phantom loaded with boron and therapeutic ratios of synovium dose/skin dose and synovium dose/bone dose were determined. Normalized to same boron loading in synovium, the values of the therapeutic ratios obtained in the present study are 12-30 times higher than the published values.

  17. THERAPEUTIC APPLICATIONS IN NUCLEAR MEDICINE

    Directory of Open Access Journals (Sweden)

    Cristofer Alan Costa Santos

    2014-12-01

    Full Text Available Due to poor understanding of the role of nuclear medicine in several disease treatments, the aim of this study was to demonstrate the main therapeutic applications of nuclear medicine as well as their characteristics and radiopharmaceuticals usage through scientific literature review. The main therapeutic applications of nuclear medicine are radio-immunotherapy with iodine-131, yttrium-90, lutetium-177 and copper-67, the radiosynovectomy with yttrium-90, rhenium-186 and gold-198 and pain palliation of osseous metastases with samarium-153, strontium-89 and phosphorus-32. The radioiodine therapy with iodine-131 stands out among therapies because it allows a highly selective treatment of thyroid associated with hyperthyroidism and differentiated thyroid cancer with favorable dosimetry to healthy tissues and with great advantage to allow the ablation of disseminated lesions due to metastases, success not achieved by traditional radiotherapy. Thus, the therapeutic nuclear medicine is an alternative tool, and often essential for definitive treatment of various diseases considered incurable once. Thus, therapeutic nuclear medicine is an alternative and often essential tool for definitive treatment of various diseases considered once incurable.

  18. Therapeutic Drug Monitoring of Lithium

    DEFF Research Database (Denmark)

    Mose, Tina; Damkier, Per; Petersen, Magnus;

    2015-01-01

    BACKGROUND: Serum lithium is monitored to ensure levels within the narrow therapeutic window. This study examines the interlaboratory variation and inaccuracy of lithium monitoring in Denmark. METHODS: In 16 samples consisting of (1) control materials (n = 4), (2) pooled patient serum (n = 5...

  19. Therapeutic apheresis in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Bambauer R

    2013-11-01

    Full Text Available Rolf Bambauer,1 Reinhard Latza,2 Carolin Bambauer,3 Daniel Burgard,4 Ralf Schiel5 1Institute for Blood Purification, Homburg, 2Laboratorium of Medicine, St Ingbert, 3Main Hospital Darmstadt, Darmstadt, 4Herz Zentrum, Cardiology, Völklingen, 5Inselklinik Heringsdorf GmbH, Seeheilbad Heringsdorf, Germany Abstract: Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a bad prognosis without treatment. Therapeutic apheresis in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 35 years. Here we provide an overview of the most important pathogenic aspects indicating that therapeutic apheresis can be a supportive therapy in some systemic autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, and inflammatory eye disease. With the introduction of novel and effective biologic agents, therapeutic apheresis is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents, and in patients with renal involvement, acute generalized vasculitis, thrombocytopenia, leucopenia, pulmonary, cardiac, or cerebral involvement. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved considerably in recent years, due in part to very aggressive therapy schemes. Keywords: therapeutic apheresis, autoimmune diseases, systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, inflammatory eye disease

  20. Scenario Writing: A Therapeutic Application.

    Science.gov (United States)

    Haddock, Billy D.

    1989-01-01

    Introduces scenario writing as useful therapeutic technique. Presents case study of woman in midst of divorce and custody fight to illustrate context in which technique was applied. Suggests additional applications. Concludes that good response is more likely for clients who possess good writing skills although other clients may use their own…

  1. Physical exercise tolerance in patients with chronic lymphoproliferative diseases after whole-body therapeutic gamma irradiation

    International Nuclear Information System (INIS)

    It is stated that physical workability remains practically at the initial level after a course of fractionated whole-body therapeutic gamma irradiation at the integral doze of 1 Gy obtained during two weeks and at the integral dose of 2 Gy obtained during 4 weeks. Tendency to decrease of systolic arterial pressure (AP) is noted under fractionated whole-body therapeutic gamma irradiation at the integral dose of 1 Gy that should be necessarily taken into account under irradiation of patients with reduced AP and patients receiving hypotensive preparations for accompanying arterial hypertension

  2. Increasing the radioprotective therapeutic efficacy of a thyphoid vaccine with sextanatoxin by combining it with methotrexate

    International Nuclear Information System (INIS)

    A thyphoid vaccine with sextaanatoxin delived to mice 4.5-5 h after γ-irradiation has a pronounced therapeutic effect: survival rate is 42% with radiation dose of 8.2 Gy (LD85/30) and 19% with radiation dose of 8.7 Gy (LD95/30). The vaccine of 2.5 and 5 mg/kg combined with methotrexate has a more pronounced therapeutic effect increasing the survival rate up to 65% (LD85/30) and up to 35-40% (LD95/30)

  3. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    International Nuclear Information System (INIS)

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8–59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m2) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4–43.9) for the entire cohort, and 22.5 months (range, 12.0–43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity (≥Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  4. Dose classification scheme for digital imaging techniques in diagnostic radiology

    International Nuclear Information System (INIS)

    Purpose: image quality in diagnostic radiology is determined in crucial extent by the signal-noise-ratio, which is proportional to the applied x-ray dose. Onward technological developments in the diagnostic radiology are therefore frequently connected with a dose increase, which subjectively is hardly or even not perceptible. The aim of this work was to define reproducible standards for image quality as a function of dose and expected therapeutical consequence in case of computed tomography of the paranasal sinuses and the upper and lower jaw (dental CT), whereby practical-clinical purposes are considered. Materials and methods: the image quality of computed tomography of the paranasal sinuses and dental CT was determined by standard deviation of the CT-numbers (pixel noise) in a region of interest of the phantom of American Association of Physicists in Medicine (AAPM phantom) and additionally in the patients CT images. The diagnostic quality of the examination was classified on the basis of patients CT images in three dose levels (low dose, standard dose and high dose). Results: the pixel noise of CT of the paranasal sinuses with soft tissue reconstruction amounts to 19.3 Hounsfield units (HU) for low dose, 8.8 HU for standard dose, and below 8 HU for high dose. The pixel noise of the dental CT with bone (high resolution) reconstruction amounts to 344 HU for low dose, 221 HU for standard dose, and below 200 HU for high dose. Suitable indications for low dose CT are the scanning of body regions with high contrast differences, like the bony delimitations of air-filled spaces of the facial bones, and radiological follow-up examinations with dedicated questions such as axis determination in dental implantology, as well as the images of objects with small diameter such as in case of children. The standard dose CT can be recommended for all cases, in which precise staging of the illness plays an indispensable role for the diagnosis and therapy planning. With high dose

  5. Dose Reduction Techniques

    CERN Document Server

    Waggoner, L O

    2000-01-01

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the sm...

  6. Cisplatin encapsulated nanoparticle as a therapeutic agent for anticancer treatment

    Science.gov (United States)

    Eka Putra, Gusti Ngurah Putu; Huang, Leaf; Hsu, Yih-Chih

    2016-03-01

    The knowledge of manipulating size of biomaterials encapsulated drug into nano-scale particles has been researched and developed in treating cancer. Cancer is the second worldwide cause of death, therefore it is critical to treat cancers challenging with therapeutic modality of various mechanisms. Our preliminary investigation has studied cisplatin encapsulated into lipid-based nanoparticle and examined the therapeutic effect on xenografted animal model. We used mice with tumor volume ranging from 195 to 214 mm3 and then few mice were grouped into three groups including: control (PBS), lipid platinum chloride (LPC) nanoparticles and CDDP (cis-diamminedichloroplatinum(II) at dose of 3mg cisplatin /kg body weight. The effect of the treatment was observed for 12 days post-injection. It showed that LPC NPs demonstrated a better therapeutic effect compared to CDDP at same 3mg cisplatin/kg drug dose of tumor size reduction, 96.6% and 11.1% respectively. In addition, mouse body weight loss of LPC, CDDP and PBS treated group are 12.1%, 24.3% and 1.4%. It means that by compared to CDDP group, LPC group demonstrated less side effect as not much reduction of body weight have found. Our findings have shown to be a potential modality to further investigate as a feasible cancer therapy modality.

  7. Gut microbiota and tacrolimus dosing in kidney transplantation.

    Directory of Open Access Journals (Sweden)

    John R Lee

    Full Text Available Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5 or did not require such an increase (Dose Stable Group, n=14. We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2 ± 1.1 mg/day vs. 3.8 ± 0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6 ± 2.4 mg/day vs. 3.3 ± 1.5 mg/day, respectively, P<0.001. Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses. Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01 and had a coefficient ± standard error of 1.0 ± 0.6 (P=0.08 after multivariable linear

  8. Multiple-dose acetaminophen pharmacokinetics.

    Science.gov (United States)

    Sahajwalla, C G; Ayres, J W

    1991-09-01

    Four different treatments of acetaminophen (Tylenol) were administered in multiple doses to eight healthy volunteers. Each treatment (325, 650, 825, and 1000 mg) was administered five times at 6-h intervals. Saliva acetaminophen concentration versus time profiles were determined. Noncompartmental pharmacokinetic parameters were calculated and compared to determine whether acetaminophen exhibited linear or dose-dependent pharmacokinetics. For doses less than or equal to 18 mg/kg, area under the curve (AUC), half-life (t1/2), mean residence time (MRT), and ratio of AUC to dose for the first dose were compared with the last dose. No statistically significant differences were observed in dose-corrected AUC for the first or last dose among subjects or treatments. Half-lives and MRT were not significantly different among treatments for the first or the last dose. Statistically significant differences in t1/2 and MRT were noted (p less than 0.05) among subjects for the last dose. A plot of AUC versus dose for the first and the last doses exhibited a linear relationship. Dose-corrected saliva concentration versus time curves for the treatments were superimposable. Thus, acetaminophen exhibits linear pharmacokinetics for doses of 18 mg/kg or less. Plots of AUC versus dose for one subject who received doses higher than 18 mg/kg were curved, suggesting nonlinear behavior of acetaminophen in this subject. PMID:1800709

  9. Comparative evaluation of therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Radionuclide therapy employing unsealed radiotherapeutic agents has emerged as an important tool for cancer management. The development of therapeutic radiopharmaceuticals based on different types of carrier molecule and a variety of radioisotopes is being actively pursued worldwide. There have been many significant advances in this field, and many of the technical problems involved in labelling biomolecules with a variety of radionuclides have been solved. However, the assessment of the relative effectiveness of different radiopharmaceuticals for cancer therapy is a difficult task owing to the large number of variables that must be considered, some related to the biological carrier and others to the radioisotope. Comparing the therapeutic efficacy in patients is not feasible in most cases for ethical and regulatory reasons. Hence, it is important to develop laboratory methods that can be used for reliable and efficient comparative evaluation of promising therapeutic radiopharmaceuticals. The IAEA has organized several coordinated research projects (CRPs) in the field of radiopharmaceuticals that have helped Member States to acquire technologies for the production of useful radiopharmaceuticals. In one such CRP on techniques for labelling biomolecules for targeted therapy, conducted from 1998 to 2001, the participants developed several protocols and standard operating procedures for labelling peptides and antibodies with therapeutic radioisotopes. During the course of the CRP, it was recognized that successful development of therapeutic radiopharmaceuticals will require in vitro biological assays as well as appropriate tumour models for carrying out biodistribution studies of the products in order to collect data for preclinical studies. Two meetings, held in 1999 and 2001, recommended the organization of a CRP for the development of laboratory methods for comparative evaluation of therapeutic radiopharmaceuticals. Fifteen countries - Brazil, Cuba, the Czech

  10. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

    2010-09-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  11. Comparison of Traditional and Simultaneous IMRT Boost Technique Basing on Therapeutic Gain Calculation

    International Nuclear Information System (INIS)

    Two different radiotherapy techniques, a traditional one (CRT) - based on consecutive decreasing of irradiation fields during treatment, and intensity modulated radiation therapy technique (IMRT) with concomitant boost, deliver different doses to treated volumes, increasing the dose in regions of interest. The fractionation schedule differs depending on the applied technique of irradiation. The aim of this study was to compare different fractionation schedules considering tumor control and normal tissue complications. The analysis of tumor control probability (TCP) and normal tissue complication probability (NTCP) were based on the linear quadratic (LQ) model of biologically equivalent dose. A therapeutic gain (TG) formula that combines NTCP and TCP for selected irradiated volumes was introduced to compare CRT and simultaneous boost (SIB) methods. TG refers to the different doses per fraction, overall treatment time (OTT), and selected biological factors such as tumor cell and repopulation time. Therapeutic gain increases with the dose per fraction and reaches the maximum for the doses at about 3 Gy. Further increase in dose per fraction results in decrease of TG, mainly because of the escalation of NTCP. The presented TG formula allows the optimization of radiotherapy planning by comparing different treatment plans for individual patients and by selecting optimal fraction dose

  12. Low dose ionizing radiation induced acoustic neuroma: A putative link?

    Directory of Open Access Journals (Sweden)

    Sachin A Borkar

    2012-01-01

    Full Text Available Although exposure to high dose ionizing radiation (following therapeutic radiotherapy has been incriminated in the pathogenesis of many brain tumors, exposure to chronic low dose ionizing radiation has not yet been shown to be associated with tumorigenesis. The authors report a case of a 50-year-old atomic reactor scientist who received a cumulative dose of 78.9 mSv over a 10-year period and was detected to have an acoustic neuroma another 15 years later. Although there is no proof that exposure to ionizing radiation was the cause for the development of the acoustic neuroma, this case highlights the need for extended follow-up periods following exposure to low dose ionizing radiation.

  13. Effects of Proton Radiation Dose, Dose Rate and Dose Fractionation on Hematopoietic Cells in Mice

    OpenAIRE

    Ware, J.H.; Sanzari, J.; Avery, S.; Sayers, C; Krigsfeld, G.; Nuth, M.; Wan, X. S.; Rusek, A.; Kennedy, A R

    2010-01-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05–0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals...

  14. Sinigrin and Its Therapeutic Benefits

    Directory of Open Access Journals (Sweden)

    Anisha Mazumder

    2016-03-01

    Full Text Available Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds which contain high amounts of sinigrin. Since ancient times, mustard has been used by mankind for its culinary, as well as medicinal, properties. It has been systematically described and evaluated in the classical Ayurvedic texts. Studies conducted on the pharmacological activities of sinigrin have revealed anti-cancer, antibacterial, antifungal, antioxidant, anti-inflammatory, wound healing properties and biofumigation. This current review will bring concise information about the known therapeutic activities of sinigrin. However, the information on known biological activities is very limited and, hence, further studies still need to be conducted and its molecular mechanisms also need to be explored. This review on the therapeutic benefits of sinigrin can summarize current knowledge about this unique phytocompounds.

  15. [Therapeutic use of cannabis derivatives].

    Science.gov (United States)

    Benyamina, Amine; Reynaud, Michel

    2014-02-01

    The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction. PMID:24701869

  16. Doses from radiation exposure

    CERN Document Server

    Menzel, H G

    2012-01-01

    Practical implementation of the International Commission on Radiological Protection's (ICRP) system of protection requires the availability of appropriate methods and data. The work of Committee 2 is concerned with the development of reference data and methods for the assessment of internal and external radiation exposure of workers and members of the public. This involves the development of reference biokinetic and dosimetric models, reference anatomical models of the human body, and reference anatomical and physiological data. Following ICRP's 2007 Recommendations, Committee 2 has focused on the provision of new reference dose coefficients for external and internal exposure. As well as specifying changes to the radiation and tissue weighting factors used in the calculation of protection quantities, the 2007 Recommendations introduced the use of reference anatomical phantoms based on medical imaging data, requiring explicit sex averaging of male and female organ-equivalent doses in the calculation of effecti...

  17. Therapeutic surfactant-stripped frozen micelles

    Science.gov (United States)

    Zhang, Yumiao; Song, Wentao; Geng, Jumin; Chitgupi, Upendra; Unsal, Hande; Federizon, Jasmin; Rzayev, Javid; Sukumaran, Dinesh K.; Alexandridis, Paschalis; Lovell, Jonathan F.

    2016-05-01

    Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like `top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and `bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2-3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated.

  18. Site-Specific PEGylation of Therapeutic Proteins

    Directory of Open Access Journals (Sweden)

    Jonathan K. Dozier

    2015-10-01

    Full Text Available The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as well as increasing the cost of therapy. One of the main strategies to alleviate these problems is to link a polyethylene glycol (PEG group to the protein of interest. This process, called PEGylation, has grown dramatically in recent years resulting in several approved drugs. Installing a single PEG chain at a defined site in a protein is challenging. Recently, there is has been considerable research into various methods for the site-specific PEGylation of proteins. This review seeks to summarize that work and provide background and context for how site-specific PEGylation is performed. After introducing the topic of site-specific PEGylation, recent developments using chemical methods are described. That is followed by a more extensive discussion of bioorthogonal reactions and enzymatic labeling.

  19. Ascaris lumbricoides: an overview of therapeutic targets.

    Science.gov (United States)

    Hagel, Isabel; Giusti, Tatiana

    2010-10-01

    A. lumbricoides is the largest of the common nematode parasites of man and has been associated with intestinal pathology, respiratory symptoms and malnutrition in children from endemic areas. Current anthelmintic treatments have proven to be safe. However, a reduced efficacy of single dose drugs has been reported. In veterinary practice, anthelmintic drug resistance is an irreversible problem. Thus, research and development of sensitive tools for early detection of drug resistance as well as new anthelmintic approaches are urgently needed. In this review, we summarized data providing information about current drug therapy against A. lumbricoides and other intestinal helminths, new drugs in experimental trials, future drugs perspectives and the identification of immunogenic parasite molecules that may be suitable vaccine targets. In addition to the WHO recommended drugs (albendazole, mebendazole, levamisole, and pyrantel pamoate), new anthelmintic alternatives such as tribendimidine and Nitazoxanide have proved to be safe and effective against A. lumbricoides and other soil-transmitted helminthiases in human trials. Also, some new drugs for veterinary use, monepantel and cyclooctadepsipeptides (e.g., PF1022A), will probably expand future drug spectrum for human treatments. The development of genomic technology has provided a great amount of available nematode DNA sequences, coupled with new gene function data that may lead to the identification of new drug targets through efficient mining of nematode genomic databases. On the other hand, the identification of nematode antigens involved in different parasite vital functions as well as immunomodulatory molecules in animals and humans may contribute to future studies of new therapeutic approaches.

  20. Newer therapeutic molecules for multiple myeloma

    Directory of Open Access Journals (Sweden)

    Jain P

    2008-01-01

    Full Text Available Therapeutic management of multiple myeloma (MM for the last several decades has mainly involved regimens based on use of glucocorticoids and cytotoxic chemotherapeutics. Despite progress in delineating the activity of such regimens, at either conventional or high doses, MM has remained an incurable disease. This has sparked major interest in the development of novel therapies that in part capitalize on recent advances in our understanding of the biology of MM, including the molecular mechanisms by which MM cell-host bone marrow (BM interactions regulate tumor-cell growth, survival, and drug resistance in the BM milieu. Herein, we review the latest progress in the development of these novel anti-MM therapies, with major focus on therapies which have translated from preclinical evaluation to clinical application, including thalidomide and its more potent immunomodulatory derivatives (IMiD, the first-in-class proteasome inhibitor bortezomib (formerly known as PS-341. Search strategy included Medline using the terms ′Myeloma and Newer Drugs′ citations relevant to treatment guidelines issued in 1999 and 2008 were screened.

  1. What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

    Energy Technology Data Exchange (ETDEWEB)

    Gotthardt, M. [Radboud Univ. Nijmegen Medical Center, Nijmegen (Netherlands). Dept. of Nuclear Medicine; Philipps Univ., Marburg (Germany). Dept. of Nuclear Medicine; Rubner, C. [Philipps Univ., Marburg (Germany). Dept. of Nuclear Medicine; Bauhofer, A. [Philipps Univ., Marburg (DE). Inst. of Theoretical Surgery] (and others)

    2006-07-01

    Purpose: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. Patients, methods: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). Results: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n=143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n=44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p>0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76{+-}80.6 Gy versus 125.6{+-}46.3 Gy; p<0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2{+-}101.7 Gy versus 125.6{+-}46.3 Gy; p=0.0097). Conclusions: TcTUs-based determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm. (orig.)

  2. Acute radiation syndrome caused by accidental radiation exposure - therapeutic principles

    Directory of Open Access Journals (Sweden)

    Dörr Harald

    2011-11-01

    Full Text Available Abstract Fortunately radiation accidents are infrequent occurrences, but since they have the potential of large scale events like the nuclear accidents of Chernobyl and Fukushima, preparatory planning of the medical management of radiation accident victims is very important. Radiation accidents can result in different types of radiation exposure for which the diagnostic and therapeutic measures, as well as the outcomes, differ. The clinical course of acute radiation syndrome depends on the absorbed radiation dose and its distribution. Multi-organ-involvement and multi-organ-failure need be taken into account. The most vulnerable organ system to radiation exposure is the hematopoietic system. In addition to hematopoietic syndrome, radiation induced damage to the skin plays an important role in diagnostics and the treatment of radiation accident victims. The most important therapeutic principles with special reference to hematopoietic syndrome and cutaneous radiation syndrome are reviewed.

  3. Therapeutic approach to sexual abuse.

    OpenAIRE

    Furniss, T; Bingley-Miller, L; Bentovim, A

    1984-01-01

    An account is given of the development of a treatment project for sexually abused children and their families. We review incidence data which indicate that sexual abuse of children is likely to be a far more frequent problem than has been recognised and cause an appreciable degree of psychological damage. Professional responses to this are confused and treatment facilities limited. Sexual abuse is seen as an expression of severe relationship problems in the family and therapeutic provision is...

  4. Bioengineering Beige Adipose Tissue Therapeutics.

    Science.gov (United States)

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  5. Brain plasticity-based therapeutics

    OpenAIRE

    Merzenich, Michael M.; Van Vleet, Thomas M.; Nahum, Mor

    2014-01-01

    The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from (a) the more-behavioral, tra...

  6. Brain Plasticity-Based Therapeutics

    OpenAIRE

    Michael eMerzenich; Mor eNahum; Tom eVan Vleet

    2014-01-01

    The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from a) the more-behavioral, trad...

  7. DNA as Therapeutics; an Update

    OpenAIRE

    Saraswat P; Soni R; Bhandari A; Nagori B

    2009-01-01

    Human gene therapy is the introduction of new genetic material into the cells of an individual with the intention of producing a therapeutic benefit for the patient. Deoxyribonucleic acid and ribonucleic acid are used in gene therapy. Over time and with proper oversight, human gene therapy might become an effective weapon in modern medicine′s arsenal to help fight diseases such as cancer, acquired immunodeficiency syndrome, diabetes, high blood pressure, coronary heart disease, periphe...

  8. Therapeutic options for severe asthma

    OpenAIRE

    Mathew, Jilcy; Aronow, Wilbert S.; Chandy, Dipak

    2012-01-01

    As the overall prevalence of asthma has escalated in the past decades, so has the population of patients with severe asthma. This condition is often difficult to manage due to the relative limitation of effective therapeutic options for the physician and the social and economic burden of the disease on the patient. Management should include an evaluation and elimination of modifiable risk factors such as smoking, allergen exposure, obesity and non-adherence, as well as therapy for co-morbidit...

  9. Pathogenesis and new therapeutic targets

    OpenAIRE

    Mertens, Michael

    2010-01-01

    Acute lung injury and its pronounced form, acute respiratory distress syndrome, are life-threatening diseases with 190,000 patients and 74,500 deaths per year in the United States. Until now there have been no therapeutic approaches to lower morbidity and mortality, except for ventilation with small tidal volumes. This partially results from a lack of understanding of the underlying mechanism of ventilator induced acute lung injury on the alveolar and alveolar capillary level. In addition, ph...

  10. Therapeutics aspects of music education

    OpenAIRE

    Pesek, Albinca; Čagran, Branka

    2015-01-01

    Disintegration of moral value system in modern society demands changes of educational system. Education takes an important part with its effort to establish integral education. In this way, an individual develops all his potentials: physical, emotional, cognitive and mental. Music education in its therapeutic mission helps at forming harmonious personality and becomes a mediator at different activities where discrepancies do not allow a successful educational process. On the basis of the empi...

  11. Bioengineering Beige Adipose Tissue Therapeutics.

    Science.gov (United States)

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  12. Therapeutic perspectives in atopic dermatitis.

    Science.gov (United States)

    Misery, Laurent

    2011-12-01

    Therapy of atopic dermatitis should comprise emollients, topical glucocorticosteroids, or calcineurin inhibitors, phototherapies, immunosuppressants like cyclosporin A, and other treatments. All these treatments should be improved, thanks to research. But new therapeutic perspectives should be given by topical anti-inflammatory substances, selective glucocorticoid receptor agonists, probiotics, interferon γ, TNFα inhibitors, inhibition of T cells or B cells, inhibition of IgE binding, and many other possibilities.

  13. Bioengineering beige adipose tissue therapeutics

    Directory of Open Access Journals (Sweden)

    Kevin eTharp

    2015-10-01

    Full Text Available Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of UCP1-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable brown adipose tissues for human therapeutic purposes at this time.Recent developments in bioengineering, including novel hyaluronic acid based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit WAT derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of beige adipose tissue implants and their potential for the metabolic

  14. Therapeutic advances in muscular dystrophy

    OpenAIRE

    Leung, Doris G.; Wagner, Kathryn R.

    2013-01-01

    The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystr...

  15. Conotoxins that Confer Therapeutic Possibilities

    Directory of Open Access Journals (Sweden)

    John A. C. Archer

    2012-06-01

    Full Text Available Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA approved pharmaceutical drug, Ziconotide (Prialt®; Elan Pharmaceuticals, Inc. that is the synthetic equivalent of the naturally occurring ω-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD was also inferred.

  16. Conotoxins that confer therapeutic possibilities.

    Science.gov (United States)

    Essack, Magbubah; Bajic, Vladimir B; Archer, John A C

    2012-06-01

    Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt(®); Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ω-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. PMID:22822370

  17. DNA as therapeutics; an update.

    Science.gov (United States)

    Saraswat, P; Soni, R R; Bhandari, A; Nagori, B P

    2009-09-01

    Human gene therapy is the introduction of new genetic material into the cells of an individual with the intention of producing a therapeutic benefit for the patient. Deoxyribonucleic acid and ribonucleic acid are used in gene therapy. Over time and with proper oversight, human gene therapy might become an effective weapon in modern medicine's arsenal to help fight diseases such as cancer, acquired immunodeficiency syndrome, diabetes, high blood pressure, coronary heart disease, peripheral vascular disease, neurodegenerative diseases, cystic fibrosis, hemophilia and other genetic disorders. Gene therapy trials in humans are of two types, somatic and germ line gene therapy. There are many ethical, social, and commercial issues raised by the prospects of treating patients whose consent is impossible to obtain. This review summarizes deoxyribonucleic acid-based therapeutics and gene transfer technologies for the diseases that are known to be genetic in origin. Deoxyribonucleic acid-based therapeutics includes plasmids, oligonucleotides for antisense and antigene applications, deoxyribonucleic acid aptamers and deoxyribonucleic acidzymes. This review also includes current status of gene therapy and recent developments in gene therapy research. PMID:20502565

  18. DNA as therapeutics; an update

    Directory of Open Access Journals (Sweden)

    Saraswat P

    2009-01-01

    Full Text Available Human gene therapy is the introduction of new genetic material into the cells of an individual with the intention of producing a therapeutic benefit for the patient. Deoxyribonucleic acid and ribonucleic acid are used in gene therapy. Over time and with proper oversight, human gene therapy might become an effective weapon in modern medicine′s arsenal to help fight diseases such as cancer, acquired immunodeficiency syndrome, diabetes, high blood pressure, coronary heart disease, peripheral vascular disease, neurodegenerative diseases, cystic fibrosis, hemophilia and other genetic disorders. Gene therapy trials in humans are of two types, somatic and germ line gene therapy. There are many ethical, social, and commercial issues raised by the prospects of treating patients whose consent is impossible to obtain. This review summarizes deoxyribonucleic acid-based therapeutics and gene transfer technologies for the diseases that are known to be genetic in origin. Deoxyribonucleic acid-based therapeutics includes plasmids, oligonucleotides for antisense and antigene applications, deoxyribonucleic acid aptamers and deoxyribonucleic acidzymes. This review also includes current status of gene therapy and recent developments in gene therapy research.

  19. Therapeutic Tools in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Christopher J Hoimes

    2009-03-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death in the United States and has a lower survival rate than other digestive tract tumors. It remains a therapeutic challenge with limited active agents. Honing our current understanding of markers of toxicity and response, and individualizing treatment with the prognostic and therapeutic tools available are important to make a worthy impact on a patient’s course. The authors summarize selected abstracts from the ASCO Gastrointestinal Cancers Symposium, San Francisco, CA, USA, January 15-17, 2009. The Symposium featured pancreatic cancer in 84 research abstracts, of which, seven are reviewed that focus on markers of toxicity: cytidine deaminase (Abstract #151 and haptogloin (Abstract #167 as markers of gemcitabine toxicity; markers of response: use of PET scan for prognosis (Abstract #157, and correlations with CA 19-9 to postchemo-radiation resectability (Abstract #215 and time to progression (Abstract #160; and individualized applications: characterizing the phenotypic similarities between a patient tumor and the direct xenograft (Abstract #154 and a report about the poor outcome of patients with ascites (Abstract #220. Validated clinical tools that can assist in managing patients through the narrow therapeutic window are needed.

  20. Copper complexes as therapeutic agents.

    Science.gov (United States)

    Duncan, Clare; White, Anthony R

    2012-02-01

    The importance of transition metals in biological processes has been well established. Copper (Cu) is a transition metal that can exist in oxidised and reduced states. This allows it to participate in redox and catalytic chemistry, making it a suitable cofactor for a diverse range of enzymes and molecules. Cu deficiency or toxicity is implicated in a variety of pathological conditions; therefore inorganic complexes of Cu have been investigated for their therapeutic and diagnostic potential. These Cu complexes have been shown to be effective in cancer treatment due to their cytotoxic action on tumour cells. Alternatively, Cu complexes can also modulate Cu homeostasis in the brain, resulting in protective effects in several models of neurodegeneration. In other diseases such as coronary heart disease and skin disease, the success of Cu complexes as potential therapeutics will most likely be due to their ability to increase SOD activity, leading to relief of oxidative stress. This review seeks to provide a broad insight into some of the diverse actions of Cu complexes and demonstrate the strong future for these compounds as potential therapeutic agents.

  1. Therapeutic apheresis in autoimmune diseases

    Science.gov (United States)

    Bambauer, Rolf; Latza, Reinhard; Bambauer, Carolin; Burgard, Daniel; Schiel, Ralf

    2013-01-01

    Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a bad prognosis without treatment. Therapeutic apheresis in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 35 years. Here we provide an overview of the most important pathogenic aspects indicating that therapeutic apheresis can be a supportive therapy in some systemic autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, and inflammatory eye disease. With the introduction of novel and effective biologic agents, therapeutic apheresis is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents, and in patients with renal involvement, acute generalized vasculitis, thrombocytopenia, leucopenia, pulmonary, cardiac, or cerebral involvement. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved considerably in recent years, due in part to very aggressive therapy schemes.

  2. Conotoxins that confer therapeutic possibilities

    KAUST Repository

    Essack, Magbubah

    2012-06-04

    Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 2012 by the authors; licensee MDPI.

  3. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  4. Enzyme therapeutics for systemic detoxification.

    Science.gov (United States)

    Liu, Yang; Li, Jie; Lu, Yunfeng

    2015-08-01

    Life relies on numerous biochemical processes working synergistically and correctly. Certain substances disrupt these processes, inducing living organism into an abnormal state termed intoxication. Managing intoxication usually requires interventions, which is referred as detoxification. Decades of development on detoxification reveals the potential of enzymes as ideal therapeutics and antidotes, because their high substrate specificity and catalytic efficiency are essential for clearing intoxicating substances without adverse effects. However, intrinsic shortcomings of enzymes including low stability and high immunogenicity are major hurdles, which could be overcome by delivering enzymes with specially designed nanocarriers. Extensive investigations on protein delivery indicate three types of enzyme-nanocarrier architectures that show more promise than others for systemic detoxification, including liposome-wrapped enzymes, polymer-enzyme conjugates, and polymer-encapsulated enzymes. This review highlights recent advances in these nano-architectures and discusses their applications in systemic detoxifications. Therapeutic potential of various enzymes as well as associated challenges in achieving effective delivery of therapeutic enzymes will also be discussed.

  5. Possible Therapeutic Use of Loperamide for Symptoms of Lactose Intolerance

    OpenAIRE

    Szilagyi, Andrew; Torchinsky, Alick; Colacone, Antoinnette

    2000-01-01

    OBJECTIVES: To examine a potential practical therapeutic use of loperamide (Lo) to decrease the symptoms of lactose intolerance.SUBJECTS AND METHODS:  Nineteen (eight men, 11 women) healthy lactose maldigesters (18 of 19 with symptoms) underwent a 25 g lactose challenge on five separate days. Breath hydrogen was measured, areas under the curve (AUC) were calculated for 4 h, and 4 and 12 h symptom scores were recorded. After establishing baseline measurements, test doses of 4 mg, 8 mg and 12 m...

  6. Potential therapeutic strategy to treat substance abuse related disorders.

    Science.gov (United States)

    Chang, Sulie L

    2013-12-01

    The "Potential Therapeutic Strategy to Treat Substance Abuse Related Disorders" session was chaired by Dr. Sulie Chang, director of NeuroImmune Phamacology at Seton University. The four presenters (and their topics) were: Dr. Wen-zhe Ho (Miniway to stop HIV/HCV), Dr. Ru-Band Lu (Low dose of memantine in the treatment of opioid dependence in human), Dr. Ping Zhang (Treatment of alcohol-related disorders-Learning from stem/progenitor cell), and Chia-Hsiang Chen (Treatment of methamphetamine abuse: an antibody-based immunotherapy approach). PMID:25267886

  7. Potential therapeutic strategy to treat substance abuse related disorders

    OpenAIRE

    Chang, Sulie L.

    2013-01-01

    The “Potential Therapeutic Strategy to Treat Substance Abuse Related Disorders” session was chaired by Dr. Sulie Chang, director of NeuroImmune Phamacology at Seton University. The four presenters (and their topics) were: Dr. Wen-zhe Ho (Miniway to stop HIV/HCV), Dr. Ru-Band Lu (Low dose of memantine in the treatment of opioid dependence in human), Dr. Ping Zhang (Treatment of alcohol-related disorders-Learning from stem/progenitor cell), and Chia-Hsiang Chen (Treatment of methamphetamine abu...

  8. Response of SOI image sensor to therapeutic carbon ion beam

    CERN Document Server

    Matsumura, Akihiko

    2015-01-01

    Carbon ion radiotherapy is known as a less invasive cancer treatment. The radiation quality is an important parameter to evaluate the biological effect and the clinical dose from the measured physical dose. The performance of SOPHIAS detector, which is the SOI image sensor having a wide dynamic range and large active area, was tested by using therapeutic carbon ion beam at Gunma University Heavy Ion Medical Center (GHMC). It was shown that the primary carbon and secondary particles can be distinguishable by SOPHIAS detector. On the other hand, a LET dependence was observed especially at the high LET region. This phenomenon will be studied by using the device simulator together with Monte Carlo simulation.

  9. Maximizing antimalarial efficacy and the importance of dosing strategies.

    Science.gov (United States)

    Beeson, James G; Boeuf, Philippe; Fowkes, Freya J I

    2015-05-09

    Artemisinin-based combination therapies (ACTs) are the cornerstone for the treatment of malaria. However, confirmed resistance to artemisinins in South-East Asia, and reports of reduced efficacy of ACTs raise major concerns for malaria treatment and control. Without new drugs to replace artemisinins, it is essential to define dosing strategies that maximize therapeutic efficacy, limit the spread of resistance, and preserve the clinical value of ACTs. It is important to determine the extent to which reduced efficacy of ACTs reflects true resistance versus sub-optimal dosing, and quantify other factors that determine treatment failure. Pooled analyses of individual patient data from multiple clinical trials, by investigators in the Worldwide Antimalarial Resistance Network, have shown high overall efficacy for three widely used ACTs, artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine. Analyses also highlight that suboptimal dosing leads to increased risk of treatment failure, especially among children. In the most recent study, an analysis of clinical trials of artesunate-amodiaquine, widely used among children in Africa, revealed a superior efficacy for fixed-dose combination tablets compared to loose non-fixed dose combinations. This highlights the benefits of fixed-dose combinations as a practical strategy for ensuring optimal antimalarial dosing and maximizing efficacy. Please see related article: http://www.biomedcentral.com/1741-7015/13/66.

  10. What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

    NARCIS (Netherlands)

    Gotthardt, M.; Rubner, C.; Bauhofer, A.; Berce, F.; Oyen, W.J.G.; Goecke, J.; Pfestroff, A.; Schlieck, A.; Corstens, F.H.M.; Behe, M.; Behr, T.M.

    2006-01-01

    PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. PATIENTS, METHODS: Data from 187 patients who had undergone RIT for MF

  11. Dose-to-man studies

    International Nuclear Information System (INIS)

    Dose-to-Man Studies focused on developing computer data handling and computer modules which permit easy, rapid assessment of the dose to southeastern United States populations from routine or accidental releases of radionuclides to atmospheric and stream systems

  12. Evaluating dose response from flexible dose clinical trials

    Directory of Open Access Journals (Sweden)

    Baron David

    2008-01-01

    Full Text Available Abstract Background The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related. Methods To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5–20 mg/day, or patients with schizophrenia who received olanzapine (N = 172, 10–20 mg/day, we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses. Results While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong dose effects and, in some cases, reversed the apparent "negative dose effect." Conclusion While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses, the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect, which may prove useful for planning confirmatory trials.

  13. [Therapeutic strategies against myasthenia gravis].

    Science.gov (United States)

    Utsugisawa, Kimiaki; Nagane, Yuriko

    2013-05-01

    Many patients with myasthenia gravis (MG) still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of oral corticosteroids, since full remission is not common. Our analysis demonstrated that disease severity, oral corticosteroids, and depressive state are the major factors negatively associated with QOL, and that QOL of MM status patients taking CSR and is a target of treatment. In order to achieve early MM or better status with prednisolne strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved status using low-dose oral corticosteroids and calcineurin inhibitors. PMID:23777099

  14. Development of therapeutic proteins: advances and challenges

    OpenAIRE

    Akash, Muhammad Sajid Hamid; REHMAN, Kanwal; Tariq, Muhammad; Chen, Shuqing

    2015-01-01

    Therapeutic proteins have shown to be effective against a variety of diseases. Pharmaceutical companies are progressively focusing on research using proteins in search of novel effective therapeutics. The significant attention by researchers has resulted in considerable advances in the production and usage of therapeutic proteins in recent years. In the current study we focused on the understanding of therapeutic proteins and their impact on the human health care system. Advancements in the f...

  15. Milestones in Parkinson's disease therapeutics.

    Science.gov (United States)

    Rascol, Olivier; Lozano, Andres; Stern, Matthew; Poewe, Werner

    2011-05-01

    In the mid-1980s, the treatment of Parkinson's disease was quite exclusively centered on dopatherapy and was focusing on dopamine systems and motor symptoms. A few dopamine agonists and a monoamine oxidase B inhibitor (selegiline) were used as adjuncts in advanced Parkinson's disease. In the early 2010s, levodopa remains the gold standard. New insights into the organization of the basal ganglia paved the way for deep brain stimulation, especially of the subthalamic nucleus, providing spectacular improvement of drug-refractory levodopa-induced motor complications. Novel dopamine agonists (pramipexole, ropinirole, rotigotine), catecholmethyltransferase inhibitors (entacapone), and monoamine oxidase B inhibitors (rasagiline) have also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to improve motor outcomes. Using dopamine agonists early, before levodopa, proved to delay the onset of dyskinesia, although this is achieved at the price of potentially disabling daytime somnolence or impulse control disorders. The demonstration of an antidyskinetic effect of the glutamate antagonist amantadine opened the door for novel nondopaminergic approaches of Parkinson's disease therapy. More recently, nonmotor symptoms (depression, dementia, and psychosis) have been the focus of the first randomized controlled trials in this field. Despite therapeutic advances, Parkinson's disease continues to be a relentlessly progressive disorder leading to severe disability. Neuroprotective interventions able to modify the progression of Parkinson's disease have stood out as a failed therapeutic goal over the last 2 decades, despite potentially encouraging results with compounds like rasagiline. Newer molecular targets, new animal models, novel clinical trial designs, and biomarkers to assess disease modification have created hope for future therapeutic interventions. PMID:21626552

  16. Bioengineering lantibiotics for therapeutic success

    Directory of Open Access Journals (Sweden)

    Des eField

    2015-11-01

    Full Text Available Several examples of highly modified antimicrobial peptides have been described. While many such peptides are non-ribosomally synthesized, ribosomally synthesised equivalents are being discovered with increased frequency. Of the latter group, the lantibiotics continue to attract most attention. In the present review, we discuss the implementation of in vivo and in vitro engineering systems to alter, and even enhance, the antimicrobial activity, antibacterial spectrum and physico-chemical properties, including heat stability, solubility, diffusion and protease resistance, of these compounds. Additionally, we discuss the potential applications of these lantibiotics for use as therapeutics.

  17. Enactments in Psychoanalysis: Therapeutic Benefits.

    Science.gov (United States)

    Stern, Stanley

    2016-01-01

    The therapeutic benefits of enactments are addressed. Relevant literature reveals disparate conceptions about the nature and use of enactments. Clarification of the term is discussed. This analyst's theoretical and technical evolution is addressed; it is inextricably related to using enactments. How can it not be? A taxonomy of enactments is presented. The article considers that enactments may be fundamental in the evolution from orthodox to contemporary analytic technique. Assumptions underlying enactments are explored, as are guidelines for using enactments. Finally, the article posits that enactments have widened the scope of analysis and contributed to its vitality. PMID:27200466

  18. Oral High-Dose Ankaferd Administration Effects on Gastrointestinal System

    OpenAIRE

    Akbal, Erdem; Köklü, Seyfettin; Astarcı, Hesna Müzeyyen; Koçak, Erdem; Karaca, Gökhan; Beyazıt, Yavuz; Topcu, Güler; Acar, Bilgehan; Ergün, Dilek; Haznedaroğlu, İbrahim Celalettin

    2013-01-01

    Background and aims: Ankaferd Blood Stopper (ABS) is a herbal extract obtained from five different plants. It has a therapeutic potential for the management of external hemorrhage and controlling gastrointestinal bleeding. However, ABS's effects are not unknown on gastrointestinal systems. The aim of this study was to assess the effect of short- and long-term systemic exposure and gastrointestinal safety following the oral administration of high-dose ABS in rats. Methods: Eighteen healthy adu...

  19. Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys

    International Nuclear Information System (INIS)

    The radioprotective effect of indralin in rhesus monkeys was examined over 60 d following gamma irradiation. Male and female rhesus macaques (Macaca mulatta) 2-3-years-old and weighing 2.1-3.5 kg were used. Animals were exposed to total-body gamma irradiation from 60Co at a dose of 6.8 Gy (lethal dose, 100% lethality over 30 days). Indralin (40-120 mg kg-1) was administered intramuscularly 5 min prior to radiation exposure. Indralin taken at a dose of 120 mg kg-1 protected five out of six monkeys (compared with the radiation control group, in which all 10 animals died). The average effective dose of indralin in the monkeys exposed to gamma irradiation for 30 min was equal to 77.3 (63.3-94.3) mg kg-1, and the maximum tolerated dose of indralin administered to monkeys was 800 mg kg-1. Indralin reduced radiation-induced injuries in macaques, thus resulting in a less severe course of acute radiation syndrome. Delayed and less pronounced manifestation of the haemorrhagic syndrome of the disease, and milder forms of both leukopenia and anaemia were also noted. The therapeutic index for indralin, expressed as the ratio of the maximum tolerated dose to the average effective dose, was equal to 10. Therefore, indralin has a significant radioprotective effect against radiation and has a high therapeutic index in rhesus monkeys. (author)

  20. Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

    Directory of Open Access Journals (Sweden)

    William A Prescott

    2014-01-01

    Full Text Available Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

  1. Therapeutic equivalents in clinical practice.

    Science.gov (United States)

    Benson, M D

    2001-01-01

    With increasing debate over the rising expenses of health care, a variety of cost-saving measures has been attempted over the years. Use of primary care physicians as "gate keepers," reduction in the length of hospital stays, and pushing women toward vaginal birth after Cesarean section have all been utilized despite on going issues with patient satisfaction and even safety. One remarkable success in stretching health-care dollars that has often been overlooked is the prescription of therapeutic equivalents, or generic drugs. Although available on a limited basis for decades, off-brand manufacture of pharmaceuticals with identical active ingredients as those of the branded drug received a large boost through Congressional legislation in 1984 with the Hatch-Waxman Act. "Fast-track" FDA approval was initiated by Congress to introduce competition into the marketplace for drugs whose patients had expired. While giving close scrutiny to the manufacturing process and requiring the same level of regulatory supervision for factors such as bioavailability and shelf life, the Hatch-Waxman Act removed the burden and expense from generic manufacturers of proving the safety and efficacy all over again of a previously FDA-approved drug. With less than a 20% market share of all prescribed drugs in 1984, the generic drug industry has captured roughly 44% of the market in recent years while accounting for only 8% of expenditures on prescription medication. The prescription of therapeutic equivalents is one method of keeping health care costs down without compromising patient satisfaction or safety. PMID:11374660

  2. Therapeutic targeting of bile acids

    Science.gov (United States)

    Gores, Gregory J.

    2015-01-01

    The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control. PMID:26138466

  3. Therapeutic Management of Colon Cancer

    Directory of Open Access Journals (Sweden)

    Ana-Maria Todosi

    2014-09-01

    Full Text Available Colorectal cancer is a major public health problem worldwide, and a major cause of mortality and morbidity. Correct pretherapeutic staging has the role of guiding the management of colon cancer patients. The diagnosis is guided by the clinical symptoms. Chemotherapy is an important part of colon cancer treatment. Chemotherapy regimens are adapted to tumor stage and patient status and have various side effects and variable survival outcomes. International guidelines recommend different treatments depending on the presence or absence of metastases. The primary goal of treatment in nonmetastatic colon cancer is surgical removal of the tumor which could be the first step of the complex therapy or preceded by neoadjuvant therapy, depending on pretherapeutic staging. In resectable nonmetastatic tumors the preferred surgical procedure is colectomy with en bloc removal of regional lymph nodes. The extent of colectomy should be based on tumor location. The management of metastatic colon cancer also targets the therapeutic approach of the metastatic disease. Therapy is standardized and applied according to tumor stage. Surveillance has a major role in therapeutic success, reason why a time schedule and a protocol adapted to the primary lesion are essential. The goal of implementing the recommendations of international guidelines for the treatment of colon cancer is to provide a uniform treatment for this disease in view of improving overall survival of patients.

  4. Hydrogels for therapeutic cardiovascular angiogenesis.

    Science.gov (United States)

    Rufaihah, Abdul Jalil; Seliktar, Dror

    2016-01-15

    Acute myocardial infarction (MI) caused by ischemia is the most common cause of cardiac dysfunction. While growth factor or cell therapy is promising, the retention of bioactive agents in the highly vascularized myocardium is limited and prevents sustained activation needed for adequate cellular responses. Various types of biomaterials with different physical and chemical properties have been developed to improve the localized delivery of growth factor and/or cells for therapeutic angiogenesis in ischemic tissues. Hydrogels are particularly advantageous as carrier systems because they are structurally similar to the tissue extracellular matrix (ECM), they can be processed under relatively mild conditions and can be delivered in a minimally invasive manner. Moreover, hydrogels can be designed to degrade in a timely fashion that coincides with the angiogenic process. For these reasons, hydrogels have shown great potential as pro-angiogenic matrices. This paper reviews a few of the hydrogel systems currently being applied together with growth factor delivery and/or cell therapy to promote therapeutic angiogenesis in ischemic tissues, with emphasis on myocardial applications.

  5. [Radioimmunotargeting: diagnosis and therapeutic use].

    Science.gov (United States)

    Vuillez, J P

    2000-11-01

    Monoclonal antibodies labeled with a radionuclide make feasible the in vivo radioimmunotargeting of tumor cells. This targeting could be performed for diagnosis, using gamma emitters, or for therapeutic purpose when antibodies are labeled with beta- and in the future alpha-emitters. Diagnosis applications (tumor detection and caracterization), i.e. immunoscintigraphy, have been widely investigated during 20 last years. This technic appeared quite interesting, complementary of morphological imaging, and clinically useful, but difficult on a practical point of view because of several pharmacological and immunological limitations. For these reasons, despite several consequent improvements (especially two-steps or pre-targeting methods), immunoscintigraphy is currently not widely used; furthermore, other scintigraphic methods, mainly positron emission tomography with 18F-fluorodeoxyglucose, are efficient and easier to perform. On the other hand, knowledge of the biodistribution of radiolabeled antibodies allows the development of their therapeutic use, i.e. radioimmunotherapy, which represents a new method of cancer treatment. Radioimmunotherapy has several particular radiobiological and dosimetric aspects, which remain widely under investigation. Understanding of these aspects, together with a better delineation of the indications, allow to be really optimist concerning this new way of cancer treatment, as shown by clinical results that have been obtained in non Hodgkin's lymphoma. Radiolabeled immunoconjugates appears as a growing field in nuclear medicine, which sustains numerous preclinical and clinical studies. PMID:11125290

  6. A method for converting dose-to-medium to dose-to-tissue in Monte Carlo studies of gold nanoparticle-enhanced radiotherapy.

    Science.gov (United States)

    Koger, B; Kirkby, C

    2016-03-01

    Gold nanoparticles (GNPs) have shown potential in recent years as a means of therapeutic dose enhancement in radiation therapy. However, a major challenge in moving towards clinical implementation is the exact characterisation of the dose enhancement they provide. Monte Carlo studies attempt to explore this property, but they often face computational limitations when examining macroscopic scenarios. In this study, a method of converting dose from macroscopic simulations, where the medium is defined as a mixture containing both gold and tissue components, to a mean dose-to-tissue on a microscopic scale was established. Monte Carlo simulations were run for both explicitly-modeled GNPs in tissue and a homogeneous mixture of tissue and gold. A dose ratio was obtained for the conversion of dose scored in a mixture medium to dose-to-tissue in each case. Dose ratios varied from 0.69 to 1.04 for photon sources and 0.97 to 1.03 for electron sources. The dose ratio is highly dependent on the source energy as well as GNP diameter and concentration, though this effect is less pronounced for electron sources. By appropriately weighting the monoenergetic dose ratios obtained, the dose ratio for any arbitrary spectrum can be determined. This allows complex scenarios to be modeled accurately without explicitly simulating each individual GNP. PMID:26895030

  7. A method for converting dose-to-medium to dose-to-tissue in Monte Carlo studies of gold nanoparticle-enhanced radiotherapy

    Science.gov (United States)

    Koger, B.; Kirkby, C.

    2016-03-01

    Gold nanoparticles (GNPs) have shown potential in recent years as a means of therapeutic dose enhancement in radiation therapy. However, a major challenge in moving towards clinical implementation is the exact characterisation of the dose enhancement they provide. Monte Carlo studies attempt to explore this property, but they often face computational limitations when examining macroscopic scenarios. In this study, a method of converting dose from macroscopic simulations, where the medium is defined as a mixture containing both gold and tissue components, to a mean dose-to-tissue on a microscopic scale was established. Monte Carlo simulations were run for both explicitly-modeled GNPs in tissue and a homogeneous mixture of tissue and gold. A dose ratio was obtained for the conversion of dose scored in a mixture medium to dose-to-tissue in each case. Dose ratios varied from 0.69 to 1.04 for photon sources and 0.97 to 1.03 for electron sources. The dose ratio is highly dependent on the source energy as well as GNP diameter and concentration, though this effect is less pronounced for electron sources. By appropriately weighting the monoenergetic dose ratios obtained, the dose ratio for any arbitrary spectrum can be determined. This allows complex scenarios to be modeled accurately without explicitly simulating each individual GNP.

  8. The therapeutic relationship after psychiatric admission.

    LENUS (Irish Health Repository)

    Roche, Eric

    2014-03-01

    The therapeutic relationship is one of the most central and important factors in the treatment of mental health disorders. A better therapeutic relationship is associated with service engagement, medication adherence, and satisfaction with services. This study aimed to compare the demographic and clinical factors associated with the therapeutic relationship in voluntarily and involuntarily admitted psychiatric service users. We found that individuals who had been admitted involuntarily, who had a diagnosis of a psychotic disorder, and who reported higher levels of perceived pressures on admission were more likely to have a poorer therapeutic relationship with their consultant psychiatrist. Greater levels of insight and treatment satisfaction, together with higher levels of procedural justice experienced on admission, were associated with a better therapeutic relationship. We found that the level of perceived coercion on admission was not related to the therapeutic relationship. Targeted interventions to improve the therapeutic relationship, particularly for involuntarily admitted service users, are discussed.

  9. Enhancing cancer therapeutics using size-optimized magnetic fluid hyperthermia

    Science.gov (United States)

    Khandhar, Amit P.; Ferguson, R. Matthew; Simon, Julian A.; Krishnan, Kannan M.

    2012-04-01

    Magnetic fluid hyperthermia (MFH) employs heat dissipation from magnetic nanoparticles to elicit a therapeutic outcome in tumor sites, which results in either cell death (>42 °C) or damage (Fe3O4) nanoparticles (MNPs) synthesized in organic solvents and subsequently transferred to aqueous phase using a biocompatible amphiphilic polymer. Monodisperse MNPs, ˜16 nm diameter, show maximum heating efficiency, or specific loss power (watts/g Fe3O4) in a 373 kHz alternating magnetic field. Our in vitro results, for 15 min of heating, show that only 40% of cells survive for a relatively low dose (490 μg Fe/ml) of these size-optimized MNPs, compared to 80% and 90% survival fraction for 12 and 13 nm MNPs at 600 μg Fe/ml. The significant decrease in cell viability due to MNP-induced hyperthermia from only size-optimized nanoparticles demonstrates the central idea of tailoring size for a specific frequency in order to intrinsically improve the therapeutic potency of MFH by optimizing both dose and time of application.

  10. Enhancing cancer therapeutics using size-optimized magnetic fluid hyperthermia.

    Science.gov (United States)

    Khandhar, Amit P; Ferguson, R Matthew; Simon, Julian A; Krishnan, Kannan M

    2012-04-01

    Magnetic fluid hyperthermia (MFH) employs heat dissipation from magnetic nanoparticles to elicit a therapeutic outcome in tumor sites, which results in either cell death (>42 °C) or damage (monodisperse magnetite (Fe(3)O(4)) nanoparticles (MNPs) synthesized in organic solvents and subsequently transferred to aqueous phase using a biocompatible amphiphilic polymer. Monodisperse MNPs, ∼16 nm diameter, show maximum heating efficiency, or specific loss power (watts/g Fe(3)O(4)) in a 373 kHz alternating magnetic field. Our in vitro results, for 15 min of heating, show that only 40% of cells survive for a relatively low dose (490 μg Fe/ml) of these size-optimized MNPs, compared to 80% and 90% survival fraction for 12 and 13 nm MNPs at 600 μg Fe/ml. The significant decrease in cell viability due to MNP-induced hyperthermia from only size-optimized nanoparticles demonstrates the central idea of tailoring size for a specific frequency in order to intrinsically improve the therapeutic potency of MFH by optimizing both dose and time of application. PMID:22393267

  11. Juvenile rheumatoid arthritis: therapeutic perspectives.

    Science.gov (United States)

    Chikanza, Ian C

    2002-01-01

    Juvenile rheumatoid arthritis (JRA) is the most common childhood chronic systemic autoimmune inflammatory disease. The therapeutic approach to JRA has, to date, been casual and based on extensions of clinical experiences gained in the management of adult rheumatoid arthritis (RA). The physiology of inflammation has been systemically studied and this has led to the identification of specific therapeutic targets and the development of novel approaches to the management of JRA. The classical treatments of the disease such as methotrexate, sodium aurothiomalate and sulfasalazine, are not always effective in controlling RA and JRA. This has necessitated the development of novel agents for treating RA, most of which are biological in nature and are targeted at specific sites of the inflammatory cascades. These biological therapeutic strategies in RA have proved successful and are being applied in the management of JRA. These developments have been facilitated by the advances in molecular biology which have heralded the advent of biodrugs (recombinant proteins) and gene therapy, in which specific genes can be introduced locally to enhance in vivo gene expression or suppress gene(s) of interest with a view to down-regulating inflammation. Some of these biodrugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), monoclonal antibodies (infliximab, adalimumab), TNF soluble receptor constructs (etanercept) and interleukin-1 receptor antagonist (IL-1Ra) have been tested and shown to be effective in RA. Etanercept has now been licensed for JRA. Clinical trials of infliximab in JRA are planned. Studies show that the clinical effects are transient, necessitating repeated treatments and the risk of vaccination effects. Anti-inflammatory cytokines such as IL-4, IL-10, transforming growth factor-beta and interferon-beta (IFN-beta) are undergoing clinical trials. Many of these agents have to be administered parenterally and production costs are very high; thus, there is a need

  12. Therapeutic applications of octreotide in pediatric patients

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al-Hussaini

    2012-01-01

    Full Text Available Background/Aim: We report our experience with the use of octreotide as primary or adjunctive therapy in children with various gastrointestinal disorders. Patients and Methods: A pharmacy database identified patients who received octreotide for gastrointestinal diseases. Indications for octreotide use, dosing, effectiveness, and adverse events were evaluated by chart review. Results: A total of 21 patients (12 males, aged 1 month to 13 years, were evaluated. Eleven received octreotide for massive gastrointestinal bleeding caused by portal hypertension-induced lesions (n=7, typhlitis (1, Meckel′s diverticulum (1, and indefinite source (2. Blood transfusion requirements were reduced from 23±9 mL/kg (mean±SD to 8±15 mL/kg (P<0.01. Four patients with pancreatic pseudocyst and/or ascites received octreotide over 14.0±5.7 days in 2 patients. In 3 children, pancreatic pseudocyst resolved in 12±2 days and pancreatic ascites resolved in 7 days in 2. Three patients with chylothorax received octreotide for 14±7 days with complete resolution in each. Two infants with chronic diarrhea received octreotide over 11±4.2 months. Stool output decreased from 85±21 mL/kg/day to 28±18 mL/kg/day, 3 months after initiation of octreotide. The child with dumping syndrome responded to octreotide in a week. Adverse events developed in 4 patients: Q-T interval prolongation and ventricular fibrillation, hyperglycemia, growth hormone deficiency, and hypertension. Conclusion: Octreotide provides a valuable addition to the therapeutic armamentum of the pediatric gastroenterologist for a wide variety of disorders. Serious adverse events may occur and patients must be closely monitored.

  13. Therapeutic interventions in cerebral palsy.

    Science.gov (United States)

    Patel, Dilip R

    2005-11-01

    Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy. PMID:16391455

  14. Brain plasticity-based therapeutics

    Science.gov (United States)

    Merzenich, Michael M.; Van Vleet, Thomas M.; Nahum, Mor

    2014-01-01

    The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from (a) the more-behavioral, traditional clinical strategies of professional therapy practitioners, and (b) an even more widely applied pharmaceutical treatment model for neurological and psychiatric treatment domains. With that background, we shall argue that neuroplasticity-based treatments will be an important part of future best-treatment practices in neurological and psychiatric medicine. PMID:25018719

  15. Brain Plasticity-Based Therapeutics

    Directory of Open Access Journals (Sweden)

    Michael eMerzenich

    2014-06-01

    Full Text Available The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from a the more-behavioral, traditional clinical strategies of professional therapy practitioners, and b an even more widely applied pharmaceutical treatment model for neurological and psychiatric treatment domains. With that background, we shall argue that neuroplasticity-based treatments will be an important part of future best-treatment practices in neurological and psychiatric medicine.

  16. Immunogenicity of Therapeutic Protein Aggregates.

    Science.gov (United States)

    Moussa, Ehab M; Panchal, Jainik P; Moorthy, Balakrishnan S; Blum, Janice S; Joubert, Marisa K; Narhi, Linda O; Topp, Elizabeth M

    2016-02-01

    Therapeutic proteins have a propensity for aggregation during manufacturing, shipping, and storage. The presence of aggregates in protein drug products can induce adverse immune responses in patients that may affect safety and efficacy, and so it is of concern to both manufacturers and regulatory agencies. In this vein, there is a lack of understanding of the physicochemical determinants of immunological responses and a lack of standardized analytical methods to survey the molecular properties of aggregates associated with immune activation. In this review, we provide an overview of the basic immune mechanisms in the context of interactions with protein aggregates. We then critically examine the literature with emphasis on the underlying immune mechanisms as they relate to aggregate properties. Finally, we highlight the gaps in our current understanding of this issue and offer recommendations for future research. PMID:26869409

  17. Host modulation by therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sugumari Elavarasu

    2012-01-01

    Full Text Available Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs, bisphosphonates, nitrous oxide (NO synthase inhibitors, recombinant human interleukin-11 (rhIL-11, omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA, mitogen-activated protein kinase (MAPK inhibitors, nuclear factor-kappa B (NF-kb inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α are some of the therapeutic agents that have host modulation properties.

  18. Angiogenesis and Its Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2013-01-01

    Full Text Available Angiogenesis plays critical roles in human physiology that range from reproduction and fetal growth to wound healing and tissue repair. The sophisticated multistep process is tightly regulated in a spatial and temporal manner by “on-off switch signals” between angiogenic factors, extracellular matrix components, and endothelial cells. Uncontrolled angiogenesis may lead to several angiogenic disorders, including vascular insufficiency (myocardial or critical limb ischemia and vascular overgrowth (hemangiomas, vascularized tumors, and retinopathies. Thus, numerous therapeutic opportunities can be envisaged through the successful understanding and subsequent manipulation of angiogenesis. Here, we review the clinical implications of angiogenesis and discuss pro- and antiangiogenic agents that offer potential therapy for cancer and other angiogenic diseases.

  19. [Hepatocellular Carcinoma: therapeutic options 2015].

    Science.gov (United States)

    Schultheiß, Michael; Bettinger, Dominik; Neeff, Hannes P; Brunner, Thomas B; Thimme, Robert

    2015-07-01

    The incidence of hepatocellular carcinoma (HCC), a common neoplasm, is rising and the prognosis is poor. Many factors have to be taken into account when deciding on the best mode of therapy, like tumor size and number, liver function, sequelae of portal hypertension or other comorbidities. These factors are reflected in the Barcelona Clinic Liver Cancer (BCLC) classification. Resection, radiofrequency ablation (RFA) and liver transplantation can be seen as curative therapies for the early and localized HCC. For the intermediate state of the HCC, there are other therapeutic modalities in therapy available: transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT, rarer occasions), off label: stereotactic body radiation therapy (SBRT). At the moment, Sorafenib is the only option in treating advanced stages of HCC. Alternative treatment strategies, like e.g. immunological therapies, are being investigated. PMID:26182255

  20. Therapeutic target for protozoal diseases

    Science.gov (United States)

    Rathore, Dharmendar; Jani, Dewal; Nagarkatti, Rana

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  1. Leucine in Obesity: Therapeutic Prospects.

    Science.gov (United States)

    Yao, Kang; Duan, Yehui; Li, Fengna; Tan, Bie; Hou, Yongqing; Wu, Guoyao; Yin, Yulong

    2016-08-01

    Obesity develops from an imbalance of energy homeostasis and is associated with chronic low-grade inflammation in white adipose tissues (WAT). Inflammation is involved in the pathophysiology of many obesity-induced disorders including insulin resistance and diabetes. Increasing evidence has shown that dietary leucine supplementation positively affects the parameters associated with obesity and obesity-related metabolic disorders. The beneficial effects include increased loss of body weight, reduced WAT inflammation, improved lipid and glucose metabolism, enhanced mitochondrial function, and preserved lean body mass. Although these beneficial effects have not been clearly established, dietary leucine supplementation, either alone or as part of a therapeutic regimen, may be a good nutritional tool in the prevention and management of obesity and obesity-induced metabolic disorders. PMID:27256112

  2. Therapeutic directions for Parkinson's disease.

    Science.gov (United States)

    Shoulson, Ira

    2010-01-01

    The focus on disease-modifying treatments and cures for Parkinson's disease (PD) has raised expectations for quantum leaps and overshadowed incremental gains that have been slowly achieved. Large multi-center clinical trials such as DATATOP and PRECEPT keep on generating new knowledge that is relevant to clinical care as well as experimental therapeutics. The largely unforeseen relationship between circulating uric acid and the occurrence and progression of PD was developed and confirmed in these clinical trials. Systematic follow-up of clinical trial cohorts after conclusion of the interventional phase provides added value that continues to inform about natural history, state and trait biomarkers, and genotype-phenotype relationships. These efforts are enhanced by data mining, public reporting, and timely sharing of data and biological samples. PMID:20187232

  3. Massive reduction of tumour load and normalisation of hyperprolactinaemia after high dose cabergoline in metastasised prolactinoma causing thoracic syringomyelia

    OpenAIRE

    Van Uum, S. H. M.; van Alfen, N.; Wesseling, P; van Lindert, E; Pieters, G.; Nooijen, P; Hermus, A

    2004-01-01

    On administration of high dose cabergoline, 0.5 mg twice a day orally, the plasma prolactin levels decreased within one month and then normalised within 26 months. Tumour load reduced considerably but unfortunately, her signs and symptoms did not improve. This case illustrates that a high dose dopamine agonist might be an important therapeutic option in patients with a metastasised prolactinoma.

  4. Assessing the accuracy of a computerized decision support system for digoxin dosing in primary care: an observational study.

    NARCIS (Netherlands)

    Kroese, W.L.; Avery, A.J.; Savelyich, B.S.; Brown, N.S.; Schers, H.J.; Howard, R.; Hippisley-Cox, J.; Horsfield, P.

    2005-01-01

    BACKGROUND: This study was carried out as part of a European Union funded project (PharmDIS-e+), to develop and evaluate software aimed at assisting physicians with drug dosing. A drug that causes particular problems with drug dosing in primary care is digoxin because of its narrow therapeutic range

  5. Curcumin: therapeutical potential in ophthalmology.

    Science.gov (United States)

    Pescosolido, Nicola; Giannotti, Rossella; Plateroti, Andrea Maria; Pascarella, Antonia; Nebbioso, Marcella

    2014-03-01

    Curcumin (diferuloylmethane) is the main curcuminoid of the popular Indian spice turmeric (Curcuma longa). In the last 50 years, in vitro and in vivo experiments supported the main role of polyphenols and curcumin for the prevention and treatment of many different inflammatory diseases and tumors.The anti-inflammatory, antioxidant, and antitumor properties of curcumin are due to different cellular mechanisms: this compound, in fact, produces different responses in different cell types. Unfortunately, because of its low solubility and oral bioavailability, the biomedical potential of curcumin is not easy to exploit; for this reason more attention has been given to nanoparticles and liposomes, which are able to improve curcumin's bioavailability. Pharmacologically, curcumin does not show any dose-limiting toxicity when it is administered at doses of up to 8 g/day for three months. It has been demonstrated that curcumin has beneficial effects on several ocular diseases, such as chronic anterior uveitis, diabetic retinopathy, glaucoma, age-related macular degeneration, and dry eye syndrome. The purpose of this review is to report what has so far been elucidated about curcumin properties and its potential use in ophthalmology. PMID:24323538

  6. Local dose enhancement in radiation therapy: Monte Carlo simulation study

    International Nuclear Information System (INIS)

    The development of nanotechnology has boosted the use of nanoparticles in radiation therapy in order to achieve greater therapeutic ratio between tumor and healthy tissues. Gold has been shown to be most suitable to this task due to the high biocompatibility and high atomic number, which contributes to a better in vivo distribution and for the local energy deposition. As a result, this study proposes to study, nanoparticle in the tumor cell. At a range of 11 nm from the nanoparticle surface, results have shown an absorbed dose 141 times higher for the medium with the gold nanoparticle compared to the water for an incident energy spectrum with maximum photon energy of 50 keV. It was also noted that when only scattered radiation is interacting with the gold nanoparticles, the dose was 134 times higher compared to enhanced local dose that remained significant even for scattered radiation. (author)

  7. MOSFET sensitivity dependence on integrated dose from high-energy photon beams.

    Science.gov (United States)

    Tanyi, James A; Krafft, Shane P; Hagio, Tomoe; Fuss, Martin; Salter, Bill J

    2008-01-01

    The ability of a commercially available dual bias, dual MOSFET dosimetry system to measure therapeutic doses reproducibly throughout its vendor-defined dose-based lifetime has been evaluated by characterizing its sensitivity variation to integrated/cumulative doses from,high-energy (6 and 15 MV) photon radiotherapy beams. The variation of sensitivity as a function of total integrated dose was studied for three different dose-per-fraction levels; namely, 50, 200, and 1200 cGy/fraction. In standard sensitivity mode (i.e., measurements involving dose-per-fraction levels > or =100 cGy), the response of the MOSFET system to identical irradiations increased with integrated dose for both energies investigated. Dose measurement reproducibility for the low (i.e., 50 cGy) dose fractions was within 2.1% (if the system was calibrated before each in-phantom measurement) and 3.1% [if the system was calibrated prior to first use, with no intermediate calibration(s)]. Similarly, dose measurement reproducibility was between 2.2% and 6.6% for the conventional (i.e., 200 cGy) dose fractions and between 1.8% and 7.9% for escalated (i.e., 1200 cGy) dose fractions. The results of this study suggest that, due to the progressively increasing sensitivity resulting from the dual-MOSFET design, frequent calibrations are required to achieve measurement accuracy of < or =3% (within one standard deviation). PMID:18293559

  8. Editorial: advances in therapeutic glycopeptides.

    Science.gov (United States)

    Zeng, Wenbin; Chen, Yue-Lei

    2014-01-01

    Glycopeptides, peptides containing sugar β-amino acids, have significant impact on medicinal chemistry research and pharmaceutical industr. In 1956, the discovery of one classic glycopeptide, vancomycin, broke the dawn of a new age for antibacterial research. Employing glycopeptides for the therapeutic purposes used to be regarded as proposals. Owing largely to the recent improvements in separation practices, characterization techniques, synthetic methods, and biological research, these proposals have been transformed into ongoing research projects in many laboratories around the world. Previously known as antibiotics, glycopeptides have been used as chemotherapeutic, antiviral, antitubercular, antifungal, antiproliferative and apoptotic agents. Nowadays they are even considered for the development of HIV and cancer vaccines. While several of them are in clinical trials, it could be expected that in the near future, treatment regimen of such difficult diseases might be reformed accordingly. Many interesting preliminary results are being produced in this emerging area. As witnesses and practitioners in this exciting area, however, we notice that the related communication in public domain is still limited due to the relatively small number of researchers involved. Thus, we feel the necessity to compile a timely issue about the special topic "Advances in Therapeutic Glycopeptides", covering state-of-the-art research papers and expert reviews from this area. We are glad that Protein & Peptide Letters is willing to realize the idea with us. The opening paper of this issue by Dr. Voglmeir and coauthor discusses three types of PNGases in respect of their general properties and applications of the commercially available PNGases in glycopeptide and glycoprotein analysis. Dr. Liu and coauthors describe current techniques such as high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and mass spectrometry (MS), for the characterization of

  9. Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window

    Science.gov (United States)

    2016-01-01

    Background: Abundant evidence at the anatomical, electrophysiological, and molecular levels implicates metabotropic glutamate receptor subtype 5 (mGluR5) in addiction. Consistently, the effects of a wide range of doses of different mGluR5 negative allosteric modulators (NAMs) have been tested in various animal models of addiction. Here, these studies were subjected to a systematic review to find out if mGluR5 NAMs have a therapeutic potential that can be translated to the clinic. Methods: Literature on consumption/self-administration and reinstatement of drug seeking as outcomes of interest published up to April 2015 was retrieved via PubMed. The review focused on the effects of systemic (i.p., i.v., s.c.) administration of the mGluR5 NAMs 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) and 2-Methyl-6-(phenylethynyl)pyridine (MPEP) on paradigms with cocaine, ethanol, nicotine, and food in rats. Results: MTEP and MPEP were found to reduce self-administration of cocaine, ethanol, and nicotine at doses ≥1mg/kg and 2.5mg/kg, respectively. Dose-response relationship resembled a sigmoidal curve, with low doses not reaching statistical significance and high doses reliably inhibiting self-administration of drugs of abuse. Importantly, self-administration of cocaine, ethanol, and nicotine, but not food, was reduced by MTEP and MPEP in the dose range of 1 to 2mg/kg and 2.5 to 3.2mg/kg, respectively. This dose range corresponds to approximately 50% to 80% mGluR5 occupancy. Interestingly, the limited data found in mice and monkeys showed a similar therapeutic window. Conclusion: Altogether, this review suggests a therapeutic window for mGluR5 NAMs that can be translated to the treatment of substance-related and addictive disorders. PMID:26802568

  10. Fast in vivo volume dose reconstruction via reference dose perturbation

    International Nuclear Information System (INIS)

    Purpose: Accurate on-line reconstruction of in-vivo volume dose that accounts for both machine and patient discrepancy is not clinically available. We present a simple reference-dose-perturbation algorithm that reconstructs in-vivo volume dose fast and accurately. Methods: We modelled the volume dose as a function of the fluence map and density image. Machine (output variation, jaw/leaf position errors, etc.) and patient (setup error, weight loss, etc.) discrepancies between the plan and delivery were modelled as perturbation of the fluence map and density image, respectively. Delivered dose is modelled as perturbation of the reference dose due to change of the fluence map and density image. We used both simulated and clinical data to validate the algorithm. The planned dose was used as the reference. The reconstruction was perturbed from the reference and accounted for output-variations and the registered daily image. The reconstruction was compared with the ground truth via isodose lines and the Gamma Index. Results: For various plans and geometries, the volume doses were reconstructed in few seconds. The reconstruction generally matched well with the ground truth. For the 3%/3mm criteria, the Gamma pass rates were 98% for simulations and 95% for clinical data. The differences mainly appeared on the surface of the phantom/patient. Conclusions: A novel reference-dose-perturbation dose reconstruction model is presented. The model accounts for machine and patient discrepancy from planning. The algorithm is simple, fast, yet accurate, which makes online in-vivo 3D dose reconstruction clinically feasible.

  11. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats

    NARCIS (Netherlands)

    Cornelissen, J.B.W.J.; Giessen, van der J.W.B.; Takumi, K.; Teunis, P.F.M.; Wisselink, H.J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Prev

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

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Höglund, A Urban

    2002-01-01

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

  13. Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity

    NARCIS (Netherlands)

    Baugh, Mark; Black, Darcey; Westwood, Paul; Kinghorn, Emma; McGregor, Kieran; Bruin, John; Hamilton, William; Dempster, Maureen; Claxton, Christopher; Cai, Jiaqiang; Bennett, Jonathan; Long, Clive; Mckinnon, Heather; Vink, Paul; den Hoed, Leontien; Gorecka, Monika; Vora, Kalpit; Grant, Ethan; Percival, M. David; Boots, A. Mieke H.; van Lierop, Marie-Jose; Boots, Annemieke

    2011-01-01

    The purpose of the study was to examine the potential of inhibition of cathepsin S as a treatment for autoimmune diseases. A highly selective cathepsin S inhibitor, CSI-75, was shown to upregulate levels of the cathepsin S substrate, invariant chain Lip10, in vitro as well as in vivo in C57Bl/6 mice

  14. Penicillin G Treatment in Infective Endocarditis Patients - Does Standard Dosing Result in Therapeutic Plasma Concentrations?

    DEFF Research Database (Denmark)

    Öbrink-Hansen, Kristina; Wiggers, Henrik; Bibby, Bo Martin;

    2016-01-01

    Penicillin G is frequently used to treat infective endocarditis (IE) caused by streptococci, penicillin-susceptible staphylococci and enterococci. Appropriate antibiotic exposure is essential for survival and reduces the risk of complications and drug resistance development. We determined...

  15. Therapeutic friendliness and the development of therapeutic leverage by mental health nurses in community rehabilitation settings.

    Science.gov (United States)

    Gardner, Andrew

    2010-01-01

    In a world dominated by technology and driven by fiscal policy emphasis, the therapeutic relationship as a healing modality is still a central theme to mental health nurses (MHN) in their everyday work. This research, as part of a PhD program, used a constructivist grounded theory approach to explore the process of therapeutic relationships and professional boundaries. The current paper outlines how therapeutic friendliness provides a connection for the therapeutic relationship to develop but in doing so requires a balancing of the therapeutic relationship and constant maintenance of the professional boundary. The authors also discuss how community mental health nurses (CMHN) invest in the therapeutic relationship in order to develop a therapeutic alliance and how the alliance between the CMHN and the client facilitates the use of therapeutic leverage applied by the CMHN as part of the therapeutic process. PMID:20509798

  16. Organ Doses and Effective Doses in Pediatric Radiography: Patient-Dose Survey in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Kiljunen, T.; Tietaevaeinen, A.; Parviainen, T.; Viitala, A.; Kortesniemi, M. (Radiation Practices Regulation, Radiation and Nuclear Safety Authority, Helsinki (Finland))

    2009-01-15

    Background: Use of the effective dose in diagnostic radiology permits the radiation exposure of diverse diagnostic procedures to be quantified. Fundamental knowledge of patient doses enhances the implementation of the 'as low as reasonably achievable' (ALARA) principle. Purpose: To provide comparative information on pediatric examination protocols and patient doses in skull, sinus, chest, abdominal, and pelvic radiography examinations. Material and Methods: 24 Finnish hospitals were asked to register pediatric examination data, including patient information and examination parameters and specifications. The total number of examinations in the study was 1916 (1426 chest, 228 sinus, 96 abdominal, 94 skull, and 72 pelvic examinations). Entrance surface dose (ESD) and dose-area products (DAP) were calculated retrospectively or DAP meters were used. Organ doses and effective doses were determined using a Monte Carlo program (PCXMC). Results: There was considerable variation in examination protocols between different hospitals, indicating large variations in patient doses. Mean effective doses of different age groups ranged from 5 muSv to 14 muSv in skull and sinus examinations, from 25 muSv to 483 muSv in abdominal examinations, and from 6 muSv to 48 muSv in chest examinations. Conclusion: In chest and sinus examinations, the amount of data was extensive, allowing national pediatric diagnostic reference levels to be defined. Parameter selection in pediatric examination protocols should be harmonized in order to reduce patient doses and improve optimization

  17. Occupational dose trends in Tanzania

    International Nuclear Information System (INIS)

    This paper describes the present status of occupational radiation exposure of monitored workers in Tanzania from 1986 to 1997. The analysis of dose records observes over this period, a fluctuating trend both in the individual and collective doses. The trend is more related to the fluctuations of the number of radiation workers than to the possible radiation safety changes of the working conditions. It has been found that, the maximum annual dose for the worker in all work categories was about 18 mSv y-1. This suggests that the occupational radiation exposure in all practices satisfies the current dose limitation system. The national exposure summary shows that, the highest collective dose of 12.8 man-Sv which is 90% of the total collective dose, was due to medical applications. The applications in industry and research had a contribution of nearly 0.8 and 0.7 man-Sv respectively. From the professional point of view, the medical diagnostic radiographers received the highest collective dose of 11.2 man-Sv. Although the medical physicists recorded the minimum collective dose of nearly 0.07 man-Sv, the data shows that this profession received the highest mean dose of about 33 mSv in 12 years. Some achievements of the personnel monitoring services and suggestions for future improvement are pointed out. (author)

  18. Hanford Environmental Dose Reconstruction Project

    International Nuclear Information System (INIS)

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that populations could have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from released to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demographics, agriculture, food habits; and, environmental pathways and dose estimates

  19. Measurement of neutron dose equivalent to proton therapy patients outside of the proton radiation field

    CERN Document Server

    Yan, X; Köhler, A; Newhauser, W D

    2002-01-01

    Measurements of neutron dose equivalent values and neutron spectral fluences close to but outside of the therapeutic proton radiation field are presented. The neutron spectral fluences were determined at five locations with Bonner sphere measurements and established by unfolding techniques. More than 50 additional neutron dose equivalent values were measured with LiI and BF sub 3 thermal neutron detectors surrounded by a 25 cm polyethylene moderating sphere. For a large-field treatment, typical values of neutron dose equivalent per therapeutic proton absorbed dose, H/D, at 50 cm distance from isocenter, range from 1 mSv/Gy (at 0 deg.with respect to the proton beam axis) to 5 mSv/Gy (at 90 deg.). Experiments reveal that H/D varies significantly with the treatment technique, e.g., patient orientation, proton beam energy, and range-modulation. The relative uncertainty in H/D values is approximately 40% (one standard deviation).

  20. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate. PMID:19835869

  1. Therapeutic potential of curcumin in gastrointestinal diseases

    OpenAIRE

    Rajasekaran, Sigrid A.

    2011-01-01

    Curcumin, also known as diferuloylmethane, is derived from the plant Curcuma longa and is the active ingredient of the spice turmeric. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. More recently, curcumin’s therapeutic potential for preventing and treating various cancers is being recognized. As curcumin’s therapeutic promise is being explored more system...

  2. Therapy with I-131 in Hyperthyroidism with Doses Adjusted to Weight

    International Nuclear Information System (INIS)

    Objectives: To assess response to therapy with I-131 adjusting the dose to weight of the gland. Study Design: Retrospective and prospective. Descriptive study. Patients: A total of 146 patients was collected in the period between January 2002 and January 2007. The data were analyzed in Access database including age, sex, duration, approximate weight of the gland, dose, side effects, radiation measurement, outcome and response time. Conclusions: The therapeutic response in treatment with radioactive iodine is adequate if given the dose adjusted to the weight of the gland, without requiring excessive doses. Cases of treatment failures were predictable by even severe symptoms to those administered with high doses. Some of the patients had received prior therapy with high dose in other institutions and probably the failure to respond was due to thyroiditis and washing accelerated I-131

  3. Doses in sensitive organs during prostate treatment with a 60Co unit

    International Nuclear Information System (INIS)

    Using thermoluminiscent dosimeters the absorbed dose in the bladder, rectum and thyroid have been evaluated when 200 cGy was applied to the prostate. The treatment was applied with a 60Co unit. A water phantom was built and thermoluminiscent dosimeters were located in the position where the prostate, bladder, rectum and thyroid are located. The therapeutic beam was applied in 4 irradiations at 0, 90, 180 and 270° with the prostate at the isocenter. The TLDs readouts were used to evaluate the absorbed dose in each organ. The absorbed doses were used to estimate the effective doses and the probability of developing secondary malignacies in thyroid, rectum and bladder. - Highlights: • The absorbed doses in the bladder, rectum and thyroid were measured. • Measurements were done during prostate treatment with a 60Co unit. • TLD100s in a water phantom were used. • The effective doses were also estimated

  4. Mortality from diseases other than cancer following low doses of ionizing radiation

    DEFF Research Database (Denmark)

    Vrijheid, M; Cardis, E; Ashmore, P;

    2007-01-01

    BACKGROUND: Ionizing radiation at very high (radio-therapeutic) dose levels can cause diseases other than cancer, particularly heart diseases. There is increasing evidence that doses of the order of a few sievert (Sv) may also increase the risk of non-cancer diseases. It is not known, however......, whether such effects also occur following the lower doses and dose rates of public health concern. METHODS: We used data from an international (15-country) nuclear workers cohort study to evaluate whether mortality from diseases other than cancer is related to low doses of external ionizing radiation....... Analyses included 275 312 workers with adequate information on socioeconomic status, over 4 million person-years of follow-up and an average cumulative radiation dose of 20.7 mSv; 11 255 workers had died of non-cancer diseases. RESULTS: The excess relative risk (ERR) per Sv was 0.24 [95% CI (confidence...

  5. Therapeutic potential of cannabinoid medicines.

    Science.gov (United States)

    Robson, P J

    2014-01-01

    Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines. The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology. In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders. PMID:24006213

  6. Our experiences with therapeutic hypothermia

    Directory of Open Access Journals (Sweden)

    Petrović Milovan

    2007-01-01

    Full Text Available Introduction. The single most important clinically relevant cause of global cerebral ischemia is cardiac arrest. The estimated rate of sudden cardiac arrest is between 40 and 130 cases per 100.000 people per year. Almost 80% of patients initially resuscitated from cardiac arrest remain comatose for more than one hour. One year after cardiac arrest only 10-30% of these patients survive with good neurological outcome. The ability to survive anoxic no-flow states is dramatically increased with protective and preservative hypothermia. The results of clinical studies show a marked neuroprotective effect of mild hypothermia in resuscitation. Material and Methods. In our clinic, 12 patients were treated with therapeutic hypothermia. A combination of intravascular and external method of cooling was used according to the ILCOR (International Liaison Committee on Resuscitation guidelines. The target temperature was 33oC, while the duration of cooling was 24 hours. After that, passive rewarming was allowed. All patients also received other necessary therapy. Results. Six patients (50% had a complete neurological recovery. Two patients (16.6% had partial neurological recovery. Four patients (33.3% remained comatose. Five patients (41.66% survived, while 7 (58.33% patients died. The main cause of cardiac arrest was acute myocardial infarction (91.6%. One patient had acute myocarditis. Conclusion. Mild resuscitative hypothermia after cardiac arrest improves neurological outcome and reduces mortality in comatose survivors. .

  7. Molecular therapeutics in pancreas cancer.

    Science.gov (United States)

    Narayanan, Vignesh; Weekes, Colin D

    2016-04-15

    The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma (PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease. PMID:27096032

  8. Therapeutical approach to rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Paraskevi Gourni

    2008-10-01

    Full Text Available Rheumatoid arthritis (RA is a chronic disease characterized by inflammation of the synovial joints, and loss of the function leading to disability. The ultimate goal in managing RA is to prevent joint damage and to maintain functional ability. Although, οver the past decade, major advances have been made in our understanding of the factors that are crucial in regulating this disease, still the managment of the disease remains difficult.Aim : Τhe aim of the present study was the evaluation of the therapeutical approch on rheumatoid arthritis. The method οf this study included bibliography research from both the review and the research literature which referred to the relation between therapy and rheumatoid arthritis.Results : The majority of research studies showed thatthe main therapy on rheumatoid arthritis included medication therapy, modification of everyday living ensuring rest, physical exercise and finally surgical procedure. Individuals suffering from rheumatoid arthritis, apart from physical problems usually cope with mental disorders, that exert a negative indluence on their quality of life.Conclusively :Information and early screening of high risk may decrease the long-term consequnences on health. Monitoring from a group of specialists should serve as a cornerstone when planning a program of intervention.

  9. [Glucomannan: properties and therapeutic applications].

    Science.gov (United States)

    González Canga, A; Fernández Martínez, N; Sahagún, A M; García Vieitez, J J; Díez Liébana, M J; Calle Pardo, A P; Castro Robles, L J; Sierra Vega, M

    2004-01-01

    Glucomannan is a dietary fiber employed quite frequently in the western countries since two decades now, as its ingestion plays an important role in human health. However, eastern people have used this fiber for more than a thousand years. This dietary fiber is the main polysaccharide obtain from the tubers of the Amorphophallus konjac plant, a member of the family Araceae found in east Asia. The chemical structure of glucomannan consists, mainly, in mannose and glucose in the ratio 8:5 linked by beta (1-->4) glycosidic bonds. This soluble fiber has a extraordinarily high waterholding capacity, forming highly viscous solutions when dissolved in water. It has the highest molecular weight and viscosity of any known dietary fiber. It has been demonstrated that this product is highly effective in the treatment of obesity due to the satiety sensation that it produces; as a remedy for constipation, because it increases the faeces volume; as hypocholesterolemic agent, interfering in the transport of cholesterol and of bile acids and as hypoglycemic and hypoinsulinemic agent, probably, by delaying gastric emptying and slowering glucose delivery to the intestinal mucosa. To the beneficial properties of this fiber, several disadvantages can be added as the production of flatulence, abdominal pain, esophageal obstruction, lower gastrointestinal obstruction or even the possible modification of the bioavailability of other drugs. This paper reviews the main characteristics of glucomannan, as well as its properties, physiologic effects and therapeutic uses.

  10. Radiolanthanides in therapeutic nuclear oncology

    International Nuclear Information System (INIS)

    Radiolanthanides such as Holmium-166 (T1/2 26.8h), Samarium-153 (T1/2 46.3h) and Lutetium-177 (T1/2 6.7 days) all have beta emissions suitable for radiopharmaceutical therapy, bone marrow ablation and for pain palliation of skeletal metastases. They also emit gamma photons of energies which permit quantitative imaging on conventional gamma cameras which facilitates calculation of dosimetry in individual patients. The range of half-lives has the potential to match the irradiation of tumour cells to the residence time of the radiopharmaceutical thus minimising radiotoxicity to normal tissues. Relative ease and low cost of production of these radiolanthanides in rectors such as HIFAR at ANSTO render radiolanthanides a practical option for radiopharmaceutical treatment of cancer for patients in whom conventional therapy has failed. Radioimmunotherapy of cancer using various monoclonal antibodies targeted to specific tumor-cell antigens has been performed with Samarium-153, Holmium-166 and Lutetium-177-labelled antibodies in human tumor xenographs in nude mice and in clinical trials. The development of a large animal model of human cancer will be described, in particular in relation to improving the accuracy of prediction of dosimetry and preclinical evaluation of efficacy and toxicity of radiolanthanides in therapeutic nuclear oncology

  11. RETRACTED ARTICLE: Radiation Sialadenitis Induced by High-dose Radioactive Iodine Therapy

    OpenAIRE

    Jeong, Shin Young; Lee, Jaetae

    2010-01-01

    Radioactive iodine (131I) is accumulated in the thyroid tissue and plays an important role in the treatment of differentiated papillary and follicular cancers after thyroidectomy. Simultaneously, 131I is concentrated in the salivary glands and secreted into the saliva. Dose-related damage to the salivary parenchyma results from the 131I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of 13...

  12. Feasibility Study of Neutron Dose for Real Time Image Guided Proton Therapy: A Monte Carlo Study

    OpenAIRE

    Kim, Jin Sung; Shin, Jung Suk; Kim, Daehyun; Shin, EunHyuk; Chung, Kwangzoo; Cho, Sungkoo; Ahn, Sung Hwan; Ju, Sanggyu; Chung, Yoonsun; Jung, Sang Hoon; Han, Youngyih

    2015-01-01

    Two full rotating gantry with different nozzles (Multipurpose nozzle with MLC, Scanning Dedicated nozzle) with conventional cyclotron system is installed and under commissioning for various proton treatment options at Samsung Medical Center in Korea. The purpose of this study is to investigate neutron dose equivalent per therapeutic dose, H/D, to x-ray imaging equipment under various treatment conditions with monte carlo simulation. At first, we investigated H/D with the various modifications...

  13. Daily vancomycin dose requirements as a continuous infusion in obese versus non-obese SICU patients

    OpenAIRE

    Lin, Hsin; Yeh, Daniel Dante; Levine, Alexander R.

    2016-01-01

    Background Limited data are available assessing vancomycin concentrations in obese critically ill patients. Currently, there are no studies evaluating dosing requirements in this population who receive vancomycin administered as a continuous infusion (CI). The aim of this study was to assess whether there was a difference in the weight-based maintenance dose required to reach a therapeutic vancomycin concentration at 24 hours when given as a CI in obese versus non-obese critically ill patient...

  14. Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

    Directory of Open Access Journals (Sweden)

    Gao CH

    2014-03-01

    Full Text Available Chu-Han Gao,1 Lu-Shan Yu,2 Su Zeng,2 Yu-Wen Huang,1 Quan Zhou11Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, 2Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of ChinaBackground: Personalized medicine should be encouraged because patients are complex, and this complexity results from biological, medical (eg, demographics, genetics, polypharmacy, and multimorbidities, socioeconomic, and cultural factors. Levofloxacin (LVX is a broad-spectrum fluoroquinolone antibiotic. Awareness of personalized therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic–pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative infections. Meanwhile, new findings in LVX therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary.Methods: Relevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic–pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed.Results: In addition to limiting the use of fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic–pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX

  15. [The therapeutic efficacy of the triase preparation in experimental pancreatic exocrine insufficiency].

    Science.gov (United States)

    Beliaev, O A

    1994-01-01

    The therapeutical efficiency of the new enzyme preparation Triase which contains microbial lipase, protease, and alpha-amylase was studied in dogs with experimental pancreatic failure. Enzyme maldigestion was made by bandaging the great pancreatic duct with pancreatic trypsin injection. The daily therapeutical dose of Triase (4 tablets) eliminated dyspepsia, creatorrhoea, restored body weight. But steatorrhoea was not abolished completely. The fecal fat content decreased to 22.1% versus 33.2% for untreated dogs following 8 weeks of the experiment. The enzyme therapy led to a more rapid reduction in blood amylase and lipase activities. This testifies that pancreatitis ran less severely. PMID:7756959

  16. A proposed new therapeutic protocol for the treatment of canine mange with ivermectin.

    Science.gov (United States)

    Mueller, R S; Bettenay, S V

    1999-01-01

    Ivermectin was used orally for the treatment of generalized demodicosis or scabies in 222 dogs. The dose was increased gradually from 50 microg/kg body weight on day one, 100 microg/kg body weight on day two, 150 microg/kg body weight on day three, 200 microg/kg body weight on day four, to the final dose of 300 microg/kg body weight on day five. This dose was continued daily until resolution for demodicosis and given four times at seven-day intervals for scabies. Two patients developed clinical ivermectin toxicity after two and 10 days, respectively, and recovered once the drug was discontinued. A gradual increase of the ivermectin dose into the therapeutic range and thorough monitoring of patients during treatment are recommended when using this drug to treat patients with generalized demodicosis or scabies.

  17. Evolution of radon dose evaluation

    Directory of Open Access Journals (Sweden)

    Fujimoto Kenzo

    2004-01-01

    Full Text Available The historical change of radon dose evaluation is reviewed based on the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR reports. Since 1955, radon has been recognized as one of the important sources of exposure of the general public. However, it was not really understood that radon is the largest dose contributor until 1977 when a new concept of effective dose equivalent was introduced by International Commission on Radiological Protection. In 1982, the dose concept was also adapted by UNSCEAR and evaluated per caput dose from natural radiation. Many researches have been carried out since then. However, lots of questions have remained open in radon problems, such as the radiation weighting factor of 20 for alpha rays and the large discrepancy of risk estimation among dosimetric and epidemiological approaches.

  18. Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trouette, R.; Causse, N.; Elkhadri, M.; Caudry, M.; Maire, J.P.; Houlard, J.P.; Racaldini, L.; Demeaux, H.

    1995-12-01

    Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

  19. Stability studies of therapeutic 131I-meta-iodobenzylguanidine (131I-mIBG) using high performance liquid chromatography

    International Nuclear Information System (INIS)

    BRIT is a manufacturer and supplier of therapeutic doses (100 mCi) of the radiopharmaceutical 131I-mIBG to various nuclear medicine centers in India. The therapeutic formulation is of high radioactive concentration (>10 mCi/ml) and is thus prone to radiolytic damage during transport, storage until administration. Earlier stability studies at this laboratory were done using conventional methods like Thin Layer Chromatography (TLC) which has an inherent limitation in terms of resolution. In view of this, a suitable HPLC method has been developed and the stability of therapeutic 131I-mIBG was monitored at various conditions

  20. Therapeutic monoclonal antibody for Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Sandro eAlmeida

    2012-11-01

    therapeutic vaccine against

  1. Pediatric health, medicine, and therapeutics

    Directory of Open Access Journals (Sweden)

    Claire E Wainwright

    2011-03-01

    Full Text Available Claire E Wainwright1,21Royal Children’s Hospital, Brisbane and Queensland, Queensland, Australia; 2Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, AustraliaThe idea of children as small adults with health care needs that can be managed by extrapolation from adult studies has now largely been abandoned. We now recognize that adult health and disease are closely linked to childhood factors and the critical and ethical importance of clinical research in pediatrics is increasingly being recognized.  While funding and output from pediatric clinical research continues to lag behind health research in adults, particularly in the area of therapeutics, the last decade has thankfully seen a dramatic increase in the number of pediatric studies and particularly randomized controlled clinical trials (RCTs. Since the 1997 Food and Drug Administration (FDA Modernization Act in the United States (US and the subsequent changes in drug registration regulatory systems in the US and Europe, there has been a huge increase in the number of pediatric studies sponsored by pharmaceutical companies. In the United Kingdom, the Medicine for Children’s Research Network was established in 2005 to address the lack of clinical studies in pediatrics. Over the first five years they reported an exciting increase in the number of high quality clinical studies and on their website they have a current portfolio of over 200 pediatric studies, half of which are RCTs and half are sponsored by pharmaceutical companies. Other countries particularly across Europe are also establishing similar programs. 

  2. Therapeutic strategies in pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Leonello eFuso

    2011-04-01

    Full Text Available Pulmonary hypertension (PH is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an ideal therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

  3. Disaggregation and valuation of collective dose and global circulation dose

    International Nuclear Information System (INIS)

    This study is an extension of earlier work (Jones et al 2004 J. Radiol. Prot. 24 13-27) using an adaptation of the PC-CREAM computer model (Mayall et al 1997 NRPB-SR296 (EUR 17791 EN) (Chilton: NRPB)) applied to future discharge scenarios for the nuclear fuel reprocessing plant at Sellafield, Cumbria, UK. This work showed that, of the total 3700 person-Sv collective dose delivered to the world population over 500 years integration from a particular scenario (SF3), 95% is at levels of individual dose below 0.015 μSv y-1. The collective dose delivered at individual dose rates below 0.015 μSv y-1 reflects the contribution from globally circulating radionuclides, namely 3H, 14C, 85Kr and 129I. The methodology used in the earlier work could not break down the dose from globally circulating radionuclides into bands of individual dose; the principal aim of this study is to achieve such a breakdown. The results confirm that the global circulation dose is received in the very lowest bands i.e. all below 0.015 μSv y-1 for atmospheric discharges, and all below 0.0015 μSv y-1 for discharges to the sea in the SF3 scenario. If account is taken of the argument that the monetary value of the detriment associated with collective dose should reduce with decreasing levels of individual dose or risk (Jackson et al 2004 J. Radiol. Prot. 24 41-59; NRPB 1993 Doc. NRPB 4 (2) 75-80) then it can be shown that the value of the detriment associated with discharges in the SF3 scenario would be substantially reduced compared with that derived from current conventional assumptions

  4. Ethics Audit of a Therapeutic Recreation Course

    Science.gov (United States)

    Nisbett, Nancy; Hinton, Jennifer

    2008-01-01

    The purpose of this study was to enhance awareness of the presence of ethics education within the allied health discipline of therapeutic recreation. To achieve this end, a curriculum audit was conducted in a therapeutic recreation course to determine the existence of ethics education within the course. Included topics, methods of delivery, and…

  5. [Therapeutic education for recurrent depressive disorder].

    Science.gov (United States)

    Carde, Soufiane; Hatif, Séverine; Samama, Diane; Charbonnel, Patricia; Jouvent, Roland

    2016-01-01

    Depression is a serious and recurrent condition which can become chronic. As a complement to other therapeutic approaches, therapeutic patient education (TPE) or psychoeducation is effective. TPE groups led by a multidisciplinary hospitalisation team in a psychiatric department are thereby integrated into the global care in order to reduce relapses and improve patients' quality of life.

  6. Establishment Of Dose Correlation During Dose Mapping On Medical Devices

    International Nuclear Information System (INIS)

    This paper explains the work done during product dose mapping in order to get the correlation between doses at MINTec-Sinagama plant. Product used was medical devices in aluminium tubes packaged in cardboard kegs packaging with average weight of 12 kg per carton. 12 cartons were loaded in every one tote to give 0.2 g/ cm3 of density. Ceric cerous dosimeters were placed at specific locations as indicated in SP14: Product Dose Mapping, QMS of MINTec-Sinagama around three planes. Three processes were made at different days as a three replicates to show the reproducibility of measurements. (author)

  7. Radiation doses from medical diagnostic procedures in Canada

    International Nuclear Information System (INIS)

    This document sets out to record and analyze the doses incurred in Canada from medical procedures involving the use of ionizing radiation in a typical year. Excluded are those doses incurred during therapeutic irradiation, since they differ in scale to such a large degree and because they are used almost exclusively in treating cancer. In this we are following a precedent set by the United Nations Scientific Committee on the Effects of Ionizing Radiation. Although the International Commission on Radiological Protection (ICRP) notes that dose limits should not be applied to medical exposures, it also observes that doses in different settings for the same procedure may vary by as much as two orders of magnitude, and that there are considerable opportunities for dose reductions in diagnostic radiology. Because these data do not stand in isolation the report also encompasses a review of the relevant literature and some background comment on the evolving technology of the radiological sciences. Because there is a somewhat incomplete perception of the changes taking place in diagnostic methods we have also provided some introductory explanations of the relevant technologies. In addition, there is an analysis of at least some of the limitations on the completeness of the data which are reported here. (author)

  8. Dosimetric systems of high dose, dose rate and dose uniformity in food and medical products

    International Nuclear Information System (INIS)

    In the Instituto Peruano de Energia Nuclear (IPEN) we use the chemical dosimetry Astm-E-1026 Fricke as a standard dosimetric system of reference and different routine dosimetric systems of high doses, according to the applied doses to obtain the desired effects in the treated products and the doses range determined for each type of dosimeter. Fricke dosimetry is a chemical dosimeter in aqueous solution indicating the absorbed dose by means an increase in absorbance at a specific wavelength. A calibrated spectrophotometer with controlled temperature is used to measure absorbance. The adsorbed dose range should cover from 20 to 400 Gy, the Fricke solution is extremely sensitive to organic impurities, to traces of metal ions, in preparing chemical products of reactive grade must be used and the water purity is very important. Using the referential standard dosimetric system Fricke, was determined to March 5, 2013, using the referential standard dosimetric system Astm-1026 Fricke, were irradiated in triplicate Fricke dosimeters, to 5 irradiation times (20; 30; 40; 50 and 60 seconds) and by linear regression, the dose rate of 5.400648 kGy /h was determined in the central point of the irradiation chamber (irradiator Gamma cell 220 Excel), applying the decay formula, was compared with the obtained results by manufacturers by means the same dosimetric system in the year of its manufacture, being this to the date 5.44691 kGy /h, with an error rate of 0.85. After considering that the dosimetric solution responds to the results, we proceeded to the irradiation of a sample of 200 g of cereal instant food, 2 dosimeters were placed at the lateral ends of the central position to maximum dose and 2 dosimeters in upper and lower ends as minimum dose, they were applied same irradiation times; for statistical analysis, the maximum dose rate was 6.1006 kGy /h and the minimum dose rate of 5.2185 kGy /h; with a dose uniformity of 1.16. In medical material of micro pulverized bone for

  9. Single and multiple dose pharmacokinetics of etizolam in healthy subjects.

    Science.gov (United States)

    Fracasso, C; Confalonieri, S; Garattini, S; Caccia, S

    1991-01-01

    The pharmacokinetics of etizolam, a new thienodiazepine derivative, has been examined after single and multiple (0.5 mg tablet) (0.5 mg b.d for 1 week) oral therapeutic doses in healthy volunteers. The single-dose kinetic profile of etizolam suggested that absorption after oral dosage was reasonably rapid, the maximum plasma concentration (Cmax) being attained within 0.5-2 h in all subjects. The mean elimination half-life (t1/2) averaged 3.4 h. Consistent with this, steady-state concentration were rapidly achieved and accumulation was extremely limited. Predicted average plasma concentrations (Cp) did not differ significantly from those actually measured at steady-state, suggesting that the kinetics of etizolam was linear, at least at therapeutic doses. The mean wash-out t1/2 was comparable to the elimination t1/2 of the single dose, which means that the drug probably has no effect on hepatic microsomal enzymes and other kinetic variables after repeated dosing. At steady state plasma concentrations of the main metabolite, alpha-hydroxyetizolam, were higher and disappeared more slowly (mean t1/2 8.2 h) than those of the parent compound. Taken with the fact that in animals the metabolite shows almost the same potency of pharmacological action as etizolam, this suggests that it may contribute significantly to the clinical effects of the parent compound. Based on the kinetic characteristics of the parent drug and its metabolite, etizolam can be regarded as a short-acting benzodiazepine, with elimination kinetics between those of short-intermediate derivatives and ultra-rapidly eliminated benzodiazepines. PMID:2065698

  10. [Study toward practical use of oligonucleotide therapeutics].

    Science.gov (United States)

    Inoue, Takao; Yoshida, Tokuyuki

    2014-01-01

    Over the past decade, oligonucleotide-based therapeutics such as antisense oligonucleotides and small interfering RNAs (siRNAs) have been developed extensively. For example, mipomersen (Kynamro; ISIS Pharmaceuticals), which is a second-generation antisense oligonucleotide administered by subcutaneous injection, has recently been approved by the FDA for the treatment of homozygous familial hypercholesterolemia. On the other hands, methods for the evaluation of quality, efficacy and safety of oligonucleotide therapeutics have not been fully discussed. Furthermore, the regulatory guidance specific for oligonucleotide therapeutics has not been established yet. Under these circumstances, we started to collaborate with Osaka University and PMDA to discuss regulatory science focused on oligonucleotide therapeutics. Through the collaboration, we would like to propose the possible design of quality evaluation and preclinical safety-evaluation of oligonucleotide therapeutics. PMID:25707197

  11. Nanotechnology in Therapeutics: hydrogels and beyond

    Directory of Open Access Journals (Sweden)

    Salata OV

    2007-07-01

    Full Text Available Abstract Nanotechnology in Therapeutics: Current Technology and Applications, Edited by Nicholas A. Peppas, J. Zach Hilt and J. Brock Thomas (Horizon Bioscience, 2007 contains seventeen chapters written by leading specialists in the field of polymeric materials for drug delivery and holds wealth of background as well as state of the art material divided into four sections: "Intelligent Therapeutics and Responsive Delivery Systems for Improved Absorption and Delivery", "Therapeutic Micro- and Nanodevices", "Nanostructured Therapeutic Materials" and "Nanoparticulate Systems in Intelligent Therapy". This newly published volume provides a stimulating read and a good point of reference to researchers wishing to explore the interdisciplinary fusion of nnanotechnology and medical therapeutics. The following gives brief summary and critically reviews the book.

  12. [Health security--GMOs in therapeutics].

    Science.gov (United States)

    Trouvin, J-H

    2003-03-01

    The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security. PMID:12668948

  13. [Sanitary safety of GMOs used in therapeutics].

    Science.gov (United States)

    Trouvin, Jean-Hugues

    2002-01-01

    The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of those new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have permitted considerable therapeutic progress without compromising health security. PMID:12669359

  14. Standardization of high-dose measurement of electron and gamma ray absorbed doses and dose rates

    International Nuclear Information System (INIS)

    Intense electron beams and gamma radiation fields are used for sterilizing medical devices, treating municipal wastes, processing industrial goods, controlling parasites and pathogens, and extending the shelf-life of foods. Quality control of such radiation processes depends largely on maintaining measurement quality assurance through sound dosimetry procedures in the research leading to each process, in the commissioning of that process, and in the routine dose monitoring practices. This affords documentation as to whether satisfactory dose uniformity is maintained throughout the product and throughout the process. Therefore, dosimetry at high doses and dose rates must in many radiation processes be standardized carefully, so that 'dosimetry release' of a product is verified. This standardization is initiated through preliminary dosimetry intercomparison studies such as those sponsored recently by the IAEA. This is followed by establishing periodic exercises in traceability to national or international standards of absorbed dose and dose rate. Traceability is achieved by careful selection of dosimetry methods and proven reference dosimeters capable of giving sufficiently accurate and precise 'transfer' dose assessments: (1) they must be calibrated or have well-established radiation-yield indices; (2) their radiation response characteristics must be reproducible and cover the dose range of interest; (3) they must withstand the rigours of back-and-forth mailing between a central standardizing laboratory and radiation processing facilities, without excessive errors arising due to instabilities, dosimeter batch non-uniformities, and environmental and handling stresses. (author)

  15. Therapeutic abortion on account of x-ray examination during pregnancy

    International Nuclear Information System (INIS)

    Previous studies on radiation injury to the foetus are reviewed. Very little is known about possible injuries due to the small radiation doses in diagnostic radiology. Eleven pregnant women had one or more abdominal X-ray examinations during the first three months of pregnancy. Subsequently, 8 had therapeutic abortion, whereas 3 went to term. The case histories are reported. The calculated foetal doses range from 0.03 to 3.7 r (0.01-18.9). The author makes the following preliminary suggestions about irradiation during the first four months of pregnancy: Foetal doses below about one r do not indicate induction of abortion. Foetal doses between about one r and about ten r indicate therapeutic abortion only in the presence of additional indications. Foetal doses above about 10 r presumably always indicate abortion. One of the pregnancies that was carried to term ought to have been interrupted. Four of the induced abortions ought not to have been performed. X-ray examinations of the abdomen should not be performed during the first four months of pregnancy. In order to avoid irradiation in the early stages of pregnancy, the following routine precaution is suggested: In fertile women X-ray examination of the abdomen should be carried out only during the first ten days after a regular menstrual period of normal intensity and duration. (author)

  16. Measurement of doses to the extremities of nuclear medicine staff

    Science.gov (United States)

    Shousha, Hany A.; Farag, Hamed; Hassan, Ramadan A.

    2010-01-01

    therapeutic 131I (2.5 mSv). In conclusion, the maximum expected annual dose to extremities is less than the annual limit (500 mSv/y).

  17. Patient dose in neonatal units

    International Nuclear Information System (INIS)

    Lung disease represents one of the most life-threatening conditions in prematurely born children. In the evaluation of the neonatal chest, the primary and most important diagnostic study is therefore the chest radiograph. Since prematurely born children are very sensitive to radiation, those radiographs may lead to a significant radiation detriment. Hence, knowledge of the patient dose is necessary to justify the exposures. A study to assess the patient doses was started at the neonatal intensive care unit (NICU) of the Univ. Hospital in Leuven. Between September 2004 and September 2005, prematurely born babies underwent on average 10 X-ray examinations in the NICU. In this sample, the maximum was 78 X-ray examinations. For chest radiographs, the median entrance skin dose was 34 μGy and the median dose area product was 7.1 mGy.cm2. By means of conversion coefficients, the measured values were converted to organ doses. Organ doses were calculated for three different weight classes: extremely low birth weight infants (2500 g). The doses to the lungs for a single chest radiograph for infants with extremely low birth weights, low birth weights and normal birth weights were 24, 25 and 32 μGy, respectively. (authors)

  18. Radiation dose estimates for radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Stabin, M.G.; Stubbs, J.B.; Toohey, R.E. [Oak Ridge Inst. of Science and Education, TN (United States). Radiation Internal Dose Information Center

    1996-04-01

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.

  19. An 225Ac/213Bi generator system for therapeutic clinical applications: construction and operation

    International Nuclear Information System (INIS)

    A method for construction and operation of an 225Ac/213Bi generator capable of producing 25-100 mCi of 213Bi suitable for clinical antibody labeling is described. The generator has been designed to have an effective lifetime of several weeks, producing up to six therapeutic doses of radionuclide per day. To date, 57 clinical doses have been prepared and injected into patients using the described 213Bi generator. Factors such as radiation damage, radioprotection, iodide eluate chemistry, radiolabeling chemistry and radionuclidic purity are addressed

  20. [Therapeutic efficacy of pantothenic acid preparations in ischemic heart disease patients].

    Science.gov (United States)

    Borets, V M; Lis, M A; Pyrochkin, V M; Kishkovich, V P; Butkevich, N D

    1987-01-01

    The therapeutic effectiveness of the pantothenic acid drugs: calciipantothenas and pantethine, was studied in 182 patients with coronary heart disease and stable angina of effort. It is shown that both the drugs produce favourable effects on certain parameters of hemodynamics, on the metabolism of lipids, riboflavin and ascorbic acid. It is recommended that the administration of calciipantothenas in a dose of 300 mg/day, during 3 weeks, be included into the combined treatment of coronary patients with no manifest disorders of lipid metabolism. Patients with manifest hyperlipidemia should be administered pantethine in a dose of 500 mg/day. PMID:3590676