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Sample records for 14c-labeled therapeutic dose

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

    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. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single (14C)-Labeled Therapeutic Dose

    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 (14C)-labeled therapeutic (20 mg) dose, ∼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-N2-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/109 nucleotides. No (14C)-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 α-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 ∼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.

  3. Synthesis of carbonyl-14C labelled 'acetochlor'

    Carbonyl-14C labelled 'acetochlor' (2-chloro-N-ethoxymethyl-N-(2-ethyl-6-methylphenyl)acetamide) was prepared by chlorination of acetic-1-14C acid obtained from barium radiocarbonate to monochloroacetic-1-14C acid which was further chlorinated to monochloroacetyl-1-14C chloride. The addition reaction of this latter with 2-ethyl-6-methylene aniline gave a chloromethyl derivative the ethanolysis of which resulted in 'acetochlor' labelled in its carbonyl carbon. The overall radiochemical yield is 51%. (author)

  4. Radiochemical synthesis of 14C-labelled pesticides

    Radioisotopic derivatives of pesticides labelled with either 14C or tritium are indispensable experimental tools for toxicology or metabolism studies required for registration of new compounds. The radiochemical synthetic pathways leading to the preparation of 14C-labelled pesticides of high specific activity, good chemical/radiochemical yield, and high radiochemical purity are presented for three groups of pesticides; triazines, aryl-haloids, and organometallic compounds. (N.T.). 10 refs., 1 tab

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

    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)

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

    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)

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

    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.

  8. Biokinetic and dosimetric investigations of 14C-labeled substances in man using AMS

    Up to now, radiation dose estimates from radiopharmaceuticals, labeled with pure β-emitting radionuclides, e.g., 14C or 3H have been very uncertain. Using accelerator mass spectrometry (AMS) we have derived new and improved data for 14C-triolein and 14C-urea and are currently running a program related to the biokinetics and dosimetry of 14C-glycocholic acid and 14C-xylose. The results of our investigations have made it possible to widen the indications for the clinical use of the 14C-urea test for Helicobacter pylori infection in children. The use of ultra-low activities, which is possible with AMS (down to 1/1000 of that used for liquid scintillation counting), has opened the possibility for metabolic investigations on children as well as on other sensitive patient groups like new-borns, and pregnant or breast-feeding women. Using the full potential of AMS, new 14C-labeled drugs could be tested on humans at a much earlier stage than today, avoiding uncertain extrapolations from animal models

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

    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

  10. AMS studies of the long-term turnover of 14C-labelled fat in man

    To estimate the biokinetics of 14C-labelled fatty acids and the associated radiation absorbed dose to man, long-term retention of 14C from oral intake of glycerol tri[1-14C]oleate (triolein) has been studied using accelerator mass spectrometry (AMS). As a complement to earlier reported data for three individuals, we present here results for one person from measurements up to 4.6 yr after administration, now also including 14C-levels in fat, muscle and bone. In this subject, a total of 44% of the administered activity was recovered in the exhaled air. Fasting increased the exhalation of 14C. The 'excess' 14CO2 due to fasting had a half-life of about 400 d. AMS measurements on fat, muscle and bone biopsies taken from the same subject 4.5 yr after ingestion indicated that a small fraction of the administered activity was still present in fat. Also, bone tissue had a higher 14C specific activity than the current environmental level. No significantly increased level was found in the muscle sample

  11. Study of translocation and distribution of 14C-labelled assimilates in young apple trees

    Translocation and distribution of 14C-labelled assimilates within one shoot and between two adjacent shoots were studied in one-year old apple trees of the variety Golden Delicious grafted on stock MM-106. The shoots were 45-50 cm long, with 24-27 fully shaped leaves and an actively growing top. Top dressing of the upper developed leaf with 14CO2 results in translocation of 14C-labelled assimilates to the growing tip, but on top dressing of the lower leaf they translocate to the root system. The basic portion of the 14C-labelled assimilates from the middle leaf moves downwards while the smaller portion-upwards. The assimilates move down the stem in a spiral which in all test trees is left (looking from the cambium side). On 14CO2 dressing of the entire shoot, the 14C-labelled assimilates do not translocate to the adjacent shoot but run down to the root system. This character of assimilates distribution was preserved also in the cases when one of the shoots had previously been treated with gibberellin (0.015 per cent), alar (0.4 per cent), bent downwards or pinched off. The absence of translocation of 14C-labelled assimilates to the adjacent shoot in the specified treatments, which change the uptaking activity of the growing centers, is explained with the ability of this shoot to be selfsufficient with respect to assimlates supply. Translocation of 14C-labelled assimilates to the shoot receiving no top dressing was induced by its defoliation (leaving the growing tip and a few young leaves). (M.Ts.)

  12. Mineralization of 14C-labelled plant material by Porcellio scaber (Crustacea, Isopoda)

    Leaf litter was incubated in a mineral soil in the presence or absence of mature Porcellio scaber. The invertebrate caused an increase in the numbers of bacteria, ammonifying bacteria, actinomycetes and protozoa in the soil. The decomposition of 14C-labelled Lemna gibba was significantly increased by the presence of P. scaber as determined by the total label remaining in the soil and the changes in sugars. 14C-labelled faeces derived from L. gibba decomposed at a slower rate than the plant tissue from which it originated. (author)

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

    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.)

  14. Metabolism of 14C-labelled urea in conventional, germ-free and mono-associated rats

    This report deals with the utilization of 14C-labelled urea in conventional, defined associated and germ-free rats. With conventional animals 71.44% of the administered 14C dose can be demonstrated in the exhaled air, 0.47% in organs and 27.35% in the urine. 1.04% were found in the intestinal and fecal contents. Animals mono-associated with Proteus mirabilis have nearly the same utilization rate (59.15, 0.34, 35.98, 2% resp.). In germ-free animals 1.21% of the activity appeared in the exhaled air and showed a small part of non-enzymatic hydrolysis of urea. The excretion of 97.70% in the urine shows, that urea is absorbed from the intestine in germ-free animals. (author)

  15. Dermal penetration and systemic distribution of sup 14 C-labeled vitamin E human skin grafted athymic nude mice

    Klain, G.J.

    1989-03-13

    In vivo percutaneous penetration and tissue distribution of 14C-labeled vitamin E applied to human skin grafted onto athymic nude mice were determined. At 1 hr, mouse skin contained the highest level of radioactivity, followed by the muscle, blood, liver, lung, adipose tissue, spleen, kidney, brain, heart, and eyes. A linear increase with time in tissue radioactivity was observed throughout the 24 hr experimental period. At 4 and 24 hrs skin grafts were highly radioactive. At 4 hrs the epidermis and the upper portion of the dermis contained more radioactivity than the remaining portion of the dermis. In contrast, at 24 hrs the highest level of radioactivity was detected in the lower dermis. No radioactivity was detected in expired air while 0.2% of the dose was found in the urine. The data show that vitamin E does penetrate skin and that the dermis acts as a barrier or reservoir for this highly lipophilic compound.

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

    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)

  17. 14C-labeled lignins as substrates for the study of lignin biodegradation and transformation

    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

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

    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)

  19. Production of 14C-labeled gas in BACTEC Neisseria Differentiation kits by Neisseria cinerea

    Six strains of Neisseria cinerea were tested in BACTEC Neisseria Differentiation kits (Johnston Laboratories, Inc., Towson, Md.), and all yielded positive glucose growth indices and negative maltose and fructose growth indices. These results were similar to those achieved with Neisseria gonorrhoeae. However, most of the N. cinerea isolates tested yielded 3-h glucose growth indices that were lower than those obtained with gonococci. 14C-labeled gas was produced significantly faster by N. gonorrhoeae than by N. cinerea. Additional studies suggested that the 14C-labeled gas produced by N. cinerea was carbon dioxide. N. cinerea strains were similar to Branhamella catarrhalis strains because both species failed to produce detectable acid from glucose, maltose, sucrose, fructose, and lactose in cysteine-tryptic agar media. However, in contrast to N. cinerea strains, B. catarrhalis strains did not metabolize glucose in BACTEC Neisseria Differentiation kits

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

    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.)

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

    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)

  2. Production of 14C-labeled gas in BACTEC Neisseria Differentiation kits by Neisseria cinerea.

    Boyce, J M; Mitchell, E B; Knapp, J S; Buttke, T M

    1985-01-01

    Six strains of Neisseria cinerea were tested in BACTEC Neisseria Differentiation kits (Johnston Laboratories, Inc., Towson, Md.), and all yielded positive glucose growth indices and negative maltose and fructose growth indices. These results were similar to those achieved with Neisseria gonorrhoeae. However, most of the N. cinerea isolates tested yielded 3-h glucose growth indices that were lower than those obtained with gonococci. 14C-labeled gas was produced significantly faster (P less tha...

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

    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)

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

    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...

  5. Synthesis of carbonyl-/sup 14/C labelled 'acetochlor'

    Jablonkai, I.; Marton, A.F.; Dutka, F. (Hungarian Academy of Sciences, Budapest. Central Research Inst. for Physics)

    1982-09-20

    Carbonyl-/sup 14/C labelled 'acetochlor' (2-chloro-N-ethoxymethyl-N-(2-ethyl-6-methylphenyl)acetamide) was prepared by chlorination of acetic-1-/sup 14/C acid obtained from barium radiocarbonate to monochloroacetic-1-/sup 14/C acid which was further chlorinated to monochloroacetyl-1-/sup 14/C chloride. The addition reaction of this latter with 2-ethyl-6-methylene aniline gave a chloromethyl derivative the ethanolysis of which resulted in 'acetochlor' labelled in its carbonyl carbon. The overall radiochemical yield is 51%.

  6. Assimilation of 14C-labelled leaf fibre by the millipede Glomeris marginata (Diplopoda, Glomeridae)

    14C-labelled fibre was prepared from living leaf tissue and applied topically to standard discs of well-rotted oak litter. When the discs were consumed by millipedes under laboratory culture conditions, a mean of 38% of the ingested label was assimilated into the hemolymph and body tissues, or respired by the animals. It is argued that the method does not allow the incorporation of label into microbial tissue prior to ingestion and therefore accurately assesses the ability of the animal to assimilate the primary structural components of leaf litter. The nutritional significance of these materials and of microbial biomass ingested with the litter is discussed. (author)

  7. A study of the stability of coumaphos, 14C-labelled lindane and 14C-labelled chlorpyrifos in model cattle dip

    The study was undertaken to evaluate the stability of coumaphos, 14C-labelled lindane and chlorpyrifos insecticides/acaricides in a simulated cattle dipping vat. During the period of the study the pH of the suspension in vat increased due to addition of soil from the vacinity of cattle barn as well as due to standing in cement-concrete of the vat. The residual amounts of lindane and chiorpyrifos were estimated by counting the corresponding radioactivity in the suspension. Lindane dissipated rapidly and its half-life during the first phase was 4 d only. After standing for 3 weeks lindane residues were equivalent to 3.5% of the original amount in the suspension and 9.6% in the supernatent. Similarly, 97% of the original amount of lindane bad dissipated in the soil sediment at the end of 3 weeks, indicating that dissipation of lindane was primarily due to volatilization. Chlorpyrifos was more stable under the experimental conditions and its half life was calculated to be 22 d during the first phase of dissipation. After 3 weeks the concentration of chlorpyriphos in the suspension remained almost unchanged. However, in the supernatant its concentration increased to 115% of the initial amount. The concentration of soil-bound residues of chlopyrofos remained less than 5% of the total amount applied through out the period of study

  8. Interactions of 14C-labeled multi-walled carbon nanotubes with soil minerals in water

    Carbon nanotubes are often modified to be stable in the aqueous phase by adding extensive hydrophilic surface functional groups. The stability of such CNTs in water with soil or sediment is one critical factor controlling their environmental fate. We conducted a series of experiments to quantitatively assess the association between water dispersed multi-walled carbon nanotubes (MWCNTs) and three soil minerals (kaolinite, smectite, or shale) in aqueous solution under different sodium concentrations. 14C-labeling was used in these experiments to unambiguously quantify MWCNTs. The results showed that increasing ionic strength strongly promoted the removal of MWCNTs from aqueous phase. The removal tendency is inversely correlated with the soil minerals’ surface potential and directly correlated with their hydrophobicity. This removal can be interpreted by the extended Derjaguin–Landau–Verwey–Overbeek (EDLVO) theory especially for kaolinite and smectite. Shale, which contains large and insoluble organic materials, sorbed MWCNTs the most strongly. - Graphical abstract: The stability of multi-walled carbon nanotubes in an aqueous system containing kaolinite, smectite or shale as model soil minerals is investigated using the 14C-labeling technique. Highlights: ► The interactions between MWCNTs and kaolinite, smectite, or shale were probed. ► Surface potential and hydrophobicity of the particles governs their interactions. ► EDLVO can be used to interpret the interactions. ► Insoluble organic materials in shale strongly sorb MWCNTs.

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

    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

  10. Laboratory culture for 14C-labeling of Chlorella and Oedogonium

    Algae were cultured in experiments that attained efficient CO2 utilization permitting 14C=labeling of cells and that compared growth characteristics of unicellular Chlorella sp. and filamentous Oedogonium sp. Culture vessels were 500ml glass tubes through which air enriched to 5% CO2 was slowly metered. The tubes, used in a vertical position for growing Chlorella, were filled with culture medium and the cells kept in suspension using a mganetic stirrer. Tubes placed horizontally and half filled with medium were used for Oedogonium permitting the 3g/l. in 5 days for Chlorella and 1 g/0.5 1. in 10 days for 3g/l. in 2 days for Chlorella and 1 g/0.5 l. in 10 days for Oedogonium. Efficiency and rate of CO2 fixation, cell size and cell weight for the two algae are evaluated. (author)

  11. High sensitivity 14C-label studies in biology using accelerator mass spectrometry

    Examples are provided of the use of a method to detect 14C-labelled biomolecules at ultratrace levels. The method is capable of 1% precision on samples of a few micrograms to milligrams that contain only the natural 14C content of the material examined. This precision corresponds to about 10-16 moles of 14C per mg of total carbon. The method is, therefore, several orders of magnitude more sensitive than traditional methods that depend on radioactive decay counting. This great sensitivity is based on using accelerator mass spectrometry (AMS) to count and detect the 14C. A new laboratory has been set up to prepare biological samples for AMS measurement. Examples of initial results obtained include measurement of a neurotoxin in brain tissue, a plant hormone in a kiwifruit vine, a carcinogen in liver and a dietary mutagen in blood. The potential applications of the method are outlined. (author). 4 refs., 5 tabs., 1 fig., 2 appendices

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

    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

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

    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

  14. Long-term persistence of various 14C-labeled pesticides in soils

    The fate of the 14C-labeled herbicides ethidimuron (ETD), methabenzthiazuron (MBT), and the fungicide anilazine (ANI) in soils was evaluated after long-term aging (9–17 years) in field based lysimeters subject to crop rotation. Analysis of residual 14C activity in the soils revealed 19% (ETD soil; 0–10 cm depth), 35% (MBT soil; 0–30), and 43% (ANI soil; 0–30) of the total initially applied. Accelerated solvent extraction yielded 90% (ETD soil), 26% (MBT soil), and 41% (ANI soil) of residual pesticide 14C activity in the samples. LC-MS/MS analysis revealed the parent compounds ETD and MBT, accounting for 3% and 2% of applied active ingredient in the soil layer, as well as dihydroxy-anilazine as the primary ANI metabolite. The results for ETD and MBT were matching with values obtained from samples of a 12 year old field plot experiment. The data demonstrate the long-term persistence of these pesticides in soils based on outdoor trials. - Highlights: ► The environmental persistence of three 14C-labeled pesticides in soils is presented. ► Extract analysis revealed the pesticides and metabolites after 9–17 years of aging. ► Pesticide residues may represent a long-term soil burden. ► The bioaccessibility and/or bioavailability of long-term aged pesticide residues remain unknown. - Residual fractions of the pesticides ethidimuron, methabenzthiazuron, and metabolites of anilazine are highly persistent in soils and remain extractable after long-term environmental aging.

  15. Living roots effect on 14C-labelled root litter decomposition

    Wheat was 14C-labelled by cultivation on soil in pots, from seedling to maturity, in a chamber with constant CO2 and 14CO2 levels. The 14C-distribution was constant amongst the aerial parts, the roots and the soil in the whole pots. After cutting the plant tops, the pots were dried without disturbing the soil and root system. The pots were then incubated under controlled humidity and temperature conditions for 62 days. In the same time a second wheat cultivation was grown on one half of the pots in normal atmosphere without plant cultivation. The purpose of the work is to study the effect of living roots on decomposition of the former 14C labelled roots litter. The CO2 and the 14CO2 released from the soil were continuously measured. On incubation days 0, 18, 33 and 62, the remaining litter was separated from soil, and the organic matter was fractionated by repeated hydrolysis and NaOH extraction. Root litter disappeared faster when living roots were present than in bare soil. The accumulation and mineralization rates of humified components in soil followed two stages. While the roots of second wheat cultivation grew actively (until earing), the strong acid hydrolysable components accumulated in larger amount than in the case of bare soil. After earing, while roots activity was depressed, these components were partly mineralized and the 14CO2 release was then higher with plants than with bare soil. The humification and mineralization rate were related with living plant phenology stages. (orig.)

  16. Microbial degradation and stabilization of 14C-labeled lignins, phenols, and phenolic polymers in relation to soil humus formation

    Use of specifically 14C-labeled phenols, lignins, fungal melanins, and model humic acid polymers makes it possible to determine which of the constituent carbons of polymers are utilized most readily by the soil organisms and which are relatively more important in soil humus formation. The studies summarized in this contribution involve: (1) the decomposition in soil of specifically 14C-labeled phenols, including lignin alcohols, monolignols; phenols, and phenolic acids formed through microbial transformations of these alcohols in the free state; (2) decomposition of model and plant lignins prepared by polymerization of specifically 14C-labeled p-hydroxyclinnamyl alcohols or by incorporation of labeled lignin precursors into plants; (3) decomposition of specific carbons of model humic acid polymers and fungal melanins prepared by the action of phenolases on reaction mixtures containing 14C-labeled phenols, amino acids, peptides, or amino sugar compounds and by placing 14C- labeled phenolic compounds under the pads of appropriate fungal cultures; and (4) some comparative properties of model, fungal, and soil humic polymers and lignins. (Refs. 70)

  17. Method for evaluating the potential of 14C labeled plant polyphenols to cross the blood-brain barrier using accelerator mass spectrometry

    Bioactive compounds in botanicals may be beneficial in preventing age-related neurodegenerative diseases, but for many compounds conventional methods may be inadequate to detect if these compounds cross the blood-brain barrier or to track the pharmacokinetics in the brain. By combining a number of unique technologies it has been possible to utilize the power of AMS to study the pharmacokinetics of bioactive compounds in the brain at very low concentrations. 14C labeled compounds can be biosynthesized by plant cell suspension cultures co-incubated with radioisotopically-labeled sucrose and isolated and separated into a series of bioactive fractions. To study the pharmacokinetics and tissue distribution of 14C labeled plant polyphenols, rats were implanted with jugular catheters, subcutaneous ultrafiltration probes and brain microdialysis probes. Labeled fractions were dosed orally. Interstitial fluid (ISF) and brain microdialysate samples were taken in tandem with blood samples. It was often possible to determine 14C in blood and ISF with a β-counter. However, brain microdialysate samples 14C levels on the order of 107 atoms/sample required AMS technology. The Brain MicrodialysateAUC/SerumAUC ranged from .021- to .029, with the higher values for the glycoside fractions. By using AMS in combination with traditional methods, it is possible to study uptake by blood, distribution to ISF and determine the amount of a dose which can reach the brain and follow the pharmacokinetics in the brain.

  18. Method for evaluating the potential of {sup 14}C labeled plant polyphenols to cross the blood-brain barrier using accelerator mass spectrometry

    Janle, Elsa M., E-mail: janle@purdue.ed [Purdue University, Department of Foods and Nutrition, 700 West State Street, West Lafayette, IN 47907-0259 (United States); Lila, Mary Ann [University of Illinois, Department of Natural Resources and Environmental Sciences Urbana IL (United States); Grannan, Michael; Wood, Lauren; Higgins, Aine [Purdue University, Department of Foods and Nutrition, 700 West State Street, West Lafayette, IN 47907-0259 (United States); Yousef, Gad G.; Rogers, Randy B. [University of Illinois, Department of Natural Resources and Environmental Sciences Urbana IL (United States); Kim, Helen [University of Alabama at Birmingham, Department of Pharmacology, Birmingham AB (United States); Jackson, George S. [Purdue University, Department of Physics, West Lafayette, IN (United States); Weaver, Connie M. [Purdue University, Department of Foods and Nutrition, 700 West State Street, West Lafayette, IN 47907-0259 (United States)

    2010-04-15

    Bioactive compounds in botanicals may be beneficial in preventing age-related neurodegenerative diseases, but for many compounds conventional methods may be inadequate to detect if these compounds cross the blood-brain barrier or to track the pharmacokinetics in the brain. By combining a number of unique technologies it has been possible to utilize the power of AMS to study the pharmacokinetics of bioactive compounds in the brain at very low concentrations. {sup 14}C labeled compounds can be biosynthesized by plant cell suspension cultures co-incubated with radioisotopically-labeled sucrose and isolated and separated into a series of bioactive fractions. To study the pharmacokinetics and tissue distribution of {sup 14}C labeled plant polyphenols, rats were implanted with jugular catheters, subcutaneous ultrafiltration probes and brain microdialysis probes. Labeled fractions were dosed orally. Interstitial fluid (ISF) and brain microdialysate samples were taken in tandem with blood samples. It was often possible to determine {sup 14}C in blood and ISF with a beta-counter. However, brain microdialysate samples {sup 14}C levels on the order of 10{sup 7} atoms/sample required AMS technology. The Brain Microdialysate{sub AUC}/Serum{sub AUC} ranged from .021- to .029, with the higher values for the glycoside fractions. By using AMS in combination with traditional methods, it is possible to study uptake by blood, distribution to ISF and determine the amount of a dose which can reach the brain and follow the pharmacokinetics in the brain.

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

    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)

  20. Production of 14C-labeled rhamnolipid of n-alkane mixture

    This research was carried out to explore the possibility of the use of 14C-glucose by pseudomonas aeruginosa to produce 14C-rhamnolipid and its role in the bioremediation of n-alkanes mixture (n-C10, n-C14). In addition to show whether the bacterial cells can utilize the bio surfactant as a carbon source. The specific activity of 14C-rhamnolipid produced was 0.082 μCi/mmol indicating 1.12% yield of 14C-rhamnolipid from 14C-glucose on the basis of the recovery of radioactivity. Bacterial growth was increased in the growth medium containing 5.6 mmol rhamnolipid of a final specific activity 0,013 μCi/mmol (a mixture of 4.7 mmol non labeled + 0.9 mmol 14C-labeled rhamnolipid), such increase was due to the degradation of n-alkane (nC10, nC12 and n-C14). There was no detection for 14C-rhamnolipid inside the bacterial cells

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

    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)

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

    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. Determination of gluconeogenesis in vivo with 14C-labeled substrates

    A mitochondrial model of gluconeogenesis and the tricarboxylic acid cycle, where pyruvate is metabolized via pyruvate carboxylase and pyruvate dehydrogenase, and pyruvate kinase is examined. The effect of the rate of tricarboxylic acid flux and the rates of the three reactions of pyruvate metabolism on the labeling patterns from [14C]pyruvate and [14C]acetate are analyzed. Expressions describing the specific radioactivities and 14C distribution in glucose as a function of these rates are derived. Specific radioactivities and isotopic patterns depend markedly on the ratio of the rates of pyruvate carboxylation and decarboxylation to the rate of citrate synthesis, but the effect of phosphoenolpyruvate hydrolysis is minor. The effects of these rates on 1) specific radioactivity of phosphoenolpyruvate, 2) labeling pattern in glucose, and 3) contribution of pyruvate, acetyl-coenzyme A, and CO2 to glucose carbon are illustrated. To determine the contribution of lactate or alanine to gluconeogenesis, experiments with two compounds labeled in different carbons are required. Methods in current use to correct for the dilution of 14C in gluconeogenesis from [14C]pyruvate are shown to be erroneous. The experimental design and techniques to determine gluconeogenesis from 14C-labeled precursors are presented and illustrated with numerical examples

  4. Long-term persistence of various 14C-labeled pesticides in soils.

    Jablonowski, Nicolai D; Linden, Andreas; Köppchen, Stephan; Thiele, Björn; Hofmann, Diana; Mittelstaedt, Werner; Pütz, Thomas; Burauel, Peter

    2012-09-01

    The fate of the 14C-labeled herbicides ethidimuron (ETD), methabenzthiazuron (MBT), and the fungicide anilazine (ANI) in soils was evaluated after long-term aging (9-17 years) in field based lysimeters subject to crop rotation. Analysis of residual 14C activity in the soils revealed 19% (ETD soil; 0-10 cm depth), 35% (MBT soil; 0-30), and 43% (ANI soil; 0-30) of the total initially applied. Accelerated solvent extraction yielded 90% (ETD soil), 26% (MBT soil), and 41% (ANI soil) of residual pesticide 14C activity in the samples. LC-MS/MS analysis revealed the parent compounds ETD and MBT, accounting for 3% and 2% of applied active ingredient in the soil layer, as well as dihydroxy-anilazine as the primary ANI metabolite. The results for ETD and MBT were matching with values obtained from samples of a 12 year old field plot experiment. The data demonstrate the long-term persistence of these pesticides in soils based on outdoor trials. PMID:22591787

  5. Migration behaviour of 14C labelled bicarbonate, HTO and 131I in boom clay

    Performance assessment studies for the deep geological disposal of radioactive waste in the Boom clay indicated the importance of the radionuclides 14C and 129I. The migration properties of these radionuclides in Boom clay are studied by Flow-Through type diffusion experiments. In the diffusion tests a mixture of 14C labelled bicarbonate, tritiated water (HTO) and carrier free 131C labelled bicarbonate, tritiated water (HTO) and carrier free 131I sodium iodide (NaI) is used. The isotope 131I is used as an equivalent for 129I. The mixture allows for a good comparison of the migration behviour of the three different species. The mean value of the diffussion constant for bicarbonate is 1.8x10-6, for iodide 4.2x10-6 and for tritiated water 6.2x10-6 cm2.s-1. For the interpretation of the experiments we consider sorption (isotopic exchange), diffusion and first order chemical reaction. The results of the diffusion tests are consistent with the concept of the diffusion accessible porosity and proves the importance of this concept. The diffusion accessible porosity for both bicarbonate and iodide is 0.11. The results are important for the safety assessment of a radioactive waste repository in the clay formation. (orig.)

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

    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

  7. Decomposition of 14C-labelled plant residues in different soils and climates of Costa Rica

    The decomposition of 14C-labelled wheat straw has been studied under field and laboratory conditions since 1975 in 13 Orthents, Andepts, Tropepts, Ustolls, and other soils of Costa Rica, representing its most important groups and production zones. No reliable predictions about the degradation rate of plant residues in field soils at their natural locations can be made from data obtained under controlled laboratory studies. Although, in some cases the decomposition rates of the laboratory experiment corresponded fairly well with the ones obtained in the field, there were instances where the laboratory decomposition lags behind. The reasons for this discrepancy have not yet been clearly interpreted, but will certainly have to do with the natural climatic conditions prevailing at the particular location. It is important to do such experiments in the open field, no matter how complicated this may be. It was found after a year, that from 23 to 36 per cent of the 14C added in the wheat straw remained in the soils under field conditions. Four years later, the residual 14C was from 11 to 23 per cent. From this information it is assumed that a considerable fraction of the organic carbon in the plant residues ramains undecomposed during several years in these tropical soils, as it occurs in other soils from temperate areas of the world. (Author)

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

    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)

  9. 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

    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)

  10. Translocation of 14C-Labelled 2,4-D in Cereals

    2-methyl-4-chlorophenoxyacetic acid (MCPA) and 2,4-dichlorophenoxyacetic acid (2,4-D) often produce deformities in the straw and spikes of cereal plants when spraying before five or six leaves have developed. Barley and oat plants were given applications of 10 μl of a 0.5% solution of 14C-labelled 2,4-D (total activity, 0.3 (μCi) at the centre of the upper surface of each leaf. The experiments comprise six different stages of development: one, two, three, four, five and six leaves. This corresponds to field practice where plants with five and six leaves receive and take up nearly five i or six times as much 2,4-D as those with a single leaf. After application the plants were left 4 - 8 h under artificial light in a greenhouse. The area of application was covered with adhesive paper and then the plants were killed by the freeze-dry method or the plants were placed between several layers of warm blotting paper in a photographic drying press, where they were killed by heating to 60°C for 15 min. Afterwards the plants were mounted with rubber cement on white cartons and pressed to paper thinness in a specially constructed press. After desiccation and pressing for about a week the plants were placed on X-ray films for autoradiography: the period of exposure was three weeks. In young barley plants at the one-, two-, or three-leaf stage the radioactive 2,4-D is effectively translocated from the point of application to the stem and through the stem to the roots, thus passing through the floral and vegetative primordia. At the five- to six-leaf stage the translocation is slight and does not extend to the stem and roots or to the growing point as it does in younger plants. Oats show little translocation in the one-to two-leaf stage (in contrast to barley); 2,4-D is not transferred to the hypocotyl, the seed and the roots to such an extent as in barley. Translocation in oat plants becomes effective in the three- to four-leaf stage when 2,4-D is detected in all parts of the

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

    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.

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

    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)

  13. Incorporation of 14C-labelled potential donors of methyl groups into turimycin and platenolide glycosides by Streptomyces hygroscopicus

    The incorporation was investigated of 14C-labelled potential donors of methyl groups as e.g. methanol, formaldehyde and methionine into the macrolide antibiotic turimycin as well as in the platenolide glycosides as the shunt products of turimycin biosynthesis by Streptomyces hygroscopicus IMET 6599- R 27-158v. By contrast to 14C-methyl-D,L-methionine giving rise to equal specific labelling of both groups of secondary metabolites, the 14C-labelled methanol and formaldehyde, respectively, led to more than 30-fold higher specific labelling of the platenolide glycosides. The results suggest that, on the one hand, there is a common intermediate, the demethylplatenolide-I (DM-Pl-I), in the biosynthesis of secondary metabolites by this strain and, secondly, that there are exist alternative pathways of biological methylation of DM-Pl-I. (author)

  14. Synthesis of [14C]-labelled eicosa-5,8,11-triynoic acid and conversion to anti-inflammatory amides

    A four step synthesis of [5,6-14C]-eicosa-5,8,11-triynoic acid from [14C]-labelled acetylene is described. [14C2]-acetylene was converted to 5-chloro-[1,2-14C]-pentyne via reaction of its monolithium salt with 3-bromo-1-chloropropane. The doubly labelled 5-chloropentyne thus obtained was transformed to [5,6-14C]-hex-5-ynoic acid which was then coupled with 1-chloro-tetradeca-2,5-diyne to give the title compound. Using 2-(2-aminoethoxy)ethanol and 1-(2-hydroxyethyl)piperazine, amides which had previously been found to be potent inhibitors of the 5-lipoxygenase enzyme, were prepared from [14C-labelled eicosatriynoic acid by way of acylimidazole chemistry. (author)

  15. Biodegradation, in vitro, of two 14C-labelled lipopolysaccharides of microbial origin in Mediterranean red soil

    The author has followed biodegradation in a Mediterranean red soil of two 14C-labelled lipopolysaccharides from the rhizosphere of Brachypodium ramosum L. He concludes that: 1) Under microbial action, one of them (A1) biodegrades much more slowly than the other (A2). He attributes this protective effect to simultaneous complexing of A1 with metal ions and clays. 2) The products of decomposition of 14C lipopolysaccharides are incorporated little in the strongly-bound fractions of organic matter

  16. A microautoradiographic study of the translocation of 14C-labelled assimilates in eragrostis curvulu (Schrad.) Nees

    Microautoradiography was used to determine the cellular distribution of translocated 14C-labelled assimilates in Eragrostis curvula. The assimilates were labelled by allowing a single leaf to photosynthesize in an atmosphere containing radioactive carbon-dioxide. It was found that the phloem was the main tissue involved in translocation; there was radial translocation from the phloem to other tissues; and some 14C was transported, apparently in the gaseous form, through the lysigenous cavaties of vascular bundles

  17. Metabolism of 35S- and 14C-labeled propylthiouracil in a model in vitro system containing thyroid peroxidase

    In previous communications we described an in vitro model system containing highly purified thyroid peroxidase (TPO) for studying the mechanism of inhibition of thyroid hormone biosynthesis by the antithyroid drugs, 6-propylthiouracil (PTU) and 1-methyl-2-mercaptoimidazole (MMI). We showed that inhibition of iodination of thyroglobulin in this system may be reversible or irreversible depending on the relative concentrations of iodide and drug and the TPO concentration. Metabolism of the drugs occurred under both conditions, but was more limited under irreversible conditions of inhibition. It was of interest to examine the nature of the drug metabolites associated with reversible and irreversible conditions of inhibition. For this purpose we have employed the 35S- and 14C-labeled drugs and a recently developed reverse phase HPLC procedure. Results of a similar study with MMI were reported in an earlier communication. In the present study we report our findings with PTU. Under conditions of reversible inhibition, PTU was readily metabolized and by 15 min was reduced to a few percent of the starting value. The earliest detectable metabolite with both [35S]- and [14C]PTU was the disulfide, which reached a peak in about 15 min and then slowly declined. Coincident with the decline in the disulfide was the appearance of more polar metabolites. In the case of [35S]PTU, these corresponded to sulfate/sulfite, PTU sulfonate, and a product tentatively identified as PTU sulfinate. The latter two were also observed as 14C-labeled metabolites produced from [14C]PTU. Two nonpolar desulfurated 14C-labeled metabolites were also observed. Surprisingly, these did not correspond to either propyluracil or propyldeoxyuracil, the anticipated most likely products of PTU desulfuration. The identity of these desulfurated metabolites of PTU in the TPO model system remains to be determined

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

    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.

  19. Studies on the environmental chemistry and dissipation of 14C-labelled Deltamethrin and Amitraz in model dips

    The degradation of 14C-labelled deltamethrin under variable conditions of pH and temperature, leaching of 14C-labelled amitraz in soil columns and dissipation of these insecticides in model dipping vat was studied. Deltamethrin was stable for 28 d in buffer solutions at pH 4,7 and 8 and at temperature of 14, 28 and 35 deg. C, but degraded in a solution at pH 9. Metabolites identified by TLC corresponded to 3-phenoxybenzoic acid and 3-phenoxybenzyl alcohol. After 75 days of standing in a model dip, about 60% of the total radioactivity was found in the sediment and corresponded mainly to deltamethrin. When 14C-Amitraz was applied to soil columns, placed under outdoor conditions, 4 months later all of the radiocarbon was found in the upper 10 cm section and about 90% of the recovered radioactivity corresponded with amitraz. A study of the dissipation of amitraz in a field vat showed that after 20 d of use the concentration of amitraz in a field dip decreased from 210 μg/mL to 155 μg/mL. (author)

  20. Fate of 14C-labeled dissolved organic matter in paddy and upland soils in responding to moisture

    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). 14C labeled DOM, extracted from the 14C labeled rice plant material, was incubated in paddy and upland soils, and the mineralization to 14CO2 and incorporation into microbial biomass were analyzed. Labile and refractory components of the initial 14C labeled DOM and their respective half-lives were calculated by a double exponential model. During incubation, the mineralization of the initial 14C labeled DOM in the paddy soils was more affected by moisture than in the upland soils. The amount of 14C incorporated into the microbial biomass (2.4–11.0% of the initial DOM-14C 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 14CO2 within 100 days was 1.2–2.1-fold higher in the paddy soils (41.9–60.0% of the initial DOM-14C activity) than in the upland soils (28.7–35.7%), 2) 14C activity remaining in solution was significantly lower in the paddy soils than in the upland soils, and 3) 14C 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 indicates less aromaticity of DOM from the paddy soils than from the upland soils. At

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

    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

  2. Coumaphos dissipation, degradation and binding to sediment in a model laboratory vat system using 14C-labelled acaricide

    Dissipation and degradation of 14C-labelled coumaphos in suspension and binding to sediment was studied in a model laboratory glass vat was studied. The water in the vat was treated with a mixture of 14C-labelled and unlabelled coumaphos and initial concentration determined. Two weeks later 50 g soil was added to the suspension and 3 x 25 mL samples taken and analysis. The procedure was repeated every two weeks for 44 weeks. pH was also recorded at each sampling time. At the end of the experiment soil was extracted by using Soxhlet apparatus and by supercritical fluid extraction and concentrations of free and bound coumaphos and metabolites were determined. Very little dissipation of total 14C occurred and 88% of the initial concentration was still present at the end of 44 weeks. The 14C content in the filtrate declined to 20% but there was a corresponding increase in the 14C content of the sediment mixed with emulsion. The pH of the suspension steadily decreased with time. HPLC analysis of the filtrate, soil wash and Soxhlet extract indicated the presence of coumaphos and three metabolites chlorferon, potasan and oxygen analogue of coumaphos. Analysis of supercritical fluid extract of the sediment-bound radioactivity showed the presence of coumaphos but no metabolites. In another study filtered and washed soil from the tank was incubated with an EPTC-degrading bacterial strain, Rhodococcus TE1 to study the effect on the metabolism of coumaphos. About 10.9% of 14C was released in the incubation mixture and it contained mostly chlorferon with some oxygen analogue of coumaphos. Exposure of 14C-labelled coumaphos to U.V. and sun lamp, to study photolysis, resulted in the formation of a brown precipitate. While the 14C content in the filtrate decreased, its concentration in the precipitate increased. The filtrate contained primarily coumaphos, whereas, the precipitate contained coumaphos, chlorferon and potasan. These findings suggest that in the field vat the

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

    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)

  4. A study of dissipation, degradation and binding of 14C-labeled endosulfan to soil in model lysimeter

    The degradation, dissipation and binding of α-endosulfan in two agricultural soils and sand was studied in lysimeter system under outdoor conditions, using 14C labeled insecticide. Dissipation was rapid during the first few weeks after application. The half life of disappearance was 38 to 61 days for the soils from Cerro Punta and El Ejido, whereas, in sand it was 91 days. The insecticide degraded by oxidation at the sulfite group to the sulfate. The resultant product underwent further degradation to form 14CO2 and bound residues. Although a significant amount of 14C leached through the sand, which contained less that 0.1% organic matter, there was no leaching of endosulfan through the other two types of soil, when leaching was started immediately after treatment. (author)

  5. Measuring chlorophyll a and 14C-labeled photosynthate in aquatic angiosperms by the use of a tissue solubilizer

    A compound that quantitatively correlated with chlorophyll a could be measured fluorometrically in the extracts of leaves of three aquatic angiosperms (Myriophyllum heterophyllum Michx., Potamogeton crispus L., Elodea canadensis Michx.) treated with the tissue solubilizer BTS-450. Fluorescent characteristics of the solubilized plant tissues were stable for several weeks in the dark at temperatures up to 600C but rapidly degraded in sunlight or when acidified. 14C-Labeled photosynthate, which had been fixed by leaf discs during 1- to 10-hour exposure to H14CO3, was also readily extracted by the tissue solubilizer. Solubilizer extraction can, therefore, be use to determine both chlorophyll a content and 14C incorporation rates in the same leaf sample. The method is practical, because no grinding is required, the fluorescent characteristics of the extracts are stable, and analyses can be performed with very little plant material

  6. Measuring chlorophyll α and 14C-labeled photosynthate in aquatic angiosperms by the use of a tissue solubilizer

    A compound that quantitatively correlated with chlorophyll α could be measured fluorometrically in the extracts of leaves of three aquatic angiosperms (Myriophyllum heterophyllum Michx., Potamogeton crispus L., Elodea canadensis Michx.) treated with the tissue solubilizer BTS-450. Fluorescent characteristics of the solubilized plant tissues were stable for several weeks in the dark at temperatures up to 600C but rapidly degraded in sunlight or when acidified. 14C-Labeled photosynthate, which had been fixed by leaf discs during 1- to 10-hour exposure to H14CO3, was also readily extracted by the tissue solubilizer. Solubilizer extraction can, therefore, be used to determine both chlorophyll α content and 14C incorporation rates in the same leaf sample. The method is practical, because no grinding is required, the fluorescent characteristics of the extracts are stable, and analyses can be performed with very little plant material (about 3 milligrams)

  7. Carbohydrate metabolism in Agaricus bisporus (Lange) Imbach: metabolism of [14C] labelled sugars by sporophores and mycelium

    When growing sporophores and vegetative mycelium of Agaricus bisporus had been supplied with [14C] labelled hexoses for varying periods of time, the major compounds labelled in both forms were mannitol, trehalose, glutamate, alanine and an unidentified substance. Mannitol was strongly labelled after application of [14C] fructose but only weakly when [14C] glucose was applied. The relative rates of oxidation by sporophores of labelled mannitol, trehalose, glucose and fructose were assessed by measuring 14CO2 production. Glucose and trehalose were the most rapidly oxidized substrates. Glucosephosphatase isomerase (E.C. 5.3.1.9) was extracted from sporohores and assayed. The conversion of glucose-6-phosphate to fructose-6-phosphate by the enzyme was competitively inhibited in vitro by 6-phosphogluconate. The control of mannitol synthesis and the functions of mannitol and trehalose are discussed. (author)

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

    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

  9. Metabolism of 35S- and 14C-labeled 1-methyl-2-mercaptoimidazole in vitro and in vivo

    We previously described an in vitro incubation system for studying the mechanism of inhibition of thyroid peroxidase (TPO)-catalyzed iodination by the antithyroid drug 1-methyl-2-mercaptoimidazole (MMI). Inhibition of iodination in this system may be reversible or irreversible, depending on the relative concentrations of iodide and MMI and on the TPO concentration. Metabolism of the drug occurs under both conditions, and in the present investigation we used 35S- and 14C-labeled MMI together with reverse phase HPLC to examine the metabolic products associated with reversible and irreversible inhibition of iodination by MMI. Under conditions of reversible inhibition, MMI was rapidly metabolized and disappeared completely from the incubation mixture. With [35S]MMI, the earliest detectable 35S-labeled product was MMI disulfide, which reached a peak after a few minutes and then declined to undetectable levels. Coincident with the decrease in disulfide was the appearance of two 35S peaks, the major one corresponding to sulfate/sulfite, and the other to a component eluting at 7.5 min. Similar results were obtained for the disulfide and for the 7.5 min metabolite with [14C]MMI. The major 14C-labeled metabolite containing no S appeared to be 1-methylimidazole. Under conditions of irreversible inhibition, MMI disulfide was also the earliest detectable 35S-labeled metabolite. However, MMI decreased more slowly, and after reaching a nadir at about 6 min returned gradually to a level about halfway between the initial and the minimum value. The reformation of MMI appeared to involve the nonenzymatic disproportionation of MMI disulfide. Formation of the 7.5 min peak was also observed, but there was no formation of sulfate/sulfite

  10. Distribution and reactivity of inhaled 14C-labeled toluene diisocyanate (TDI) in rats

    Inhalation exposure to toluene diisocyanate (TDI) can result in a variety of airway diseases. Concern has been expressed that a putative carcinogenic potential of TDI exists as a result of the formation of toluenediamine (TDA) by hydrolysis of the isocyanate in the body. Results from long-term bioassays (TDI inhalation versus gavage in rats and mice) are contradictory and discrepancies do exist concerning the interpretation of adverse effects. This study was performed to analyze the distribution and reactivity of radioactively-labeled TDI using vapor exposure in a rat model system. Rats were exposed to 14C-TDI vapors at concentrations ranging from 0.026 to 0.821 ppm for 4 h. All tissues examined showed detectable quantities of radioactivity, with the airways, gastrointestinal system and blood having the highest levels which increased with exposure concentration. The concentration of radioactivity in the bloodstream after exposure was linear with respect to dose. The majority (74-87%) of the label associated with the blood was recovered in the plasma, and of this, 97-100% of the 14C existed in the form of biomolecular conjugates. Analysis of stomach contents shows that the majority of the label is also associated with high (> 10 kDa) molecular weight species. While a larger percentage (28%) of the label is found in the low molecular weight fraction relative to blood, this low molecular weight labeled material represents at least eight different components. Thus, over the vapor exposure concentrations and time tested, it appears that conjugation is the predominant reaction and that free TDA is not a primary in vivo reaction product under the conditions tested. (orig.)

  11. The effect of two soil applied fungicides - PCNB and thiram on the mineralization of 14C - labelled rice straw in soils

    The effect of PCNB and thiram was studied on the mineralization of 14C - labelled rice straw in clay and sandy loam soils for 40 days. PCNB at normal and 10-times the field application rates had no effect on the rate of 14CO2 evolution from 14C - labelled rice straw in both the soils. The rate of 14CO2 evolution in soils was unchanged by thiram at normal field application rate, but the same at 10-times field application rate retarded initially and stimulated later the rate of 14CO2 evolution. PCNB and thiram had no deleterious effect on the total mineralization of 14C - labelled rice straw in both clay and sandy loam soils at the end of 40-days incubation. (author)

  12. Distribution of 14C after oral administration of [U-14C]labeled methyl linoleate hydroperoxides and their secondary oxidation products in rats

    To study the toxicity of low molecular weight (LMW) compounds formed during the autoxidation of oils, 14C-labeled primary monomeric compounds (methyl linoleate hydroperoxides) and secondary oxidation products, i.e., polymer and LMW compounds prepared from autoxidized methyl [U-14C]linoleate hydroperoxides (MLHPO) were orally administered to rats, and their radioactive distributions in tissues and organs were compared. The polymeric fraction consisted mainly of dimers of MLHPO. For the LMW fraction, 4-hydroxy-2-nonenal, 8-hydroxy methyl octanoate and 10-formyl methyl-9-decenoate were identified as major constituents by gas chromatography-mass spectrometry (GC-MS) after chemical reduction and derivatization. When LMW compounds were administered to rats, 14CO2 expiration and the excreted radioactivity in urine in 12 hr were significantly higher than those from polymer or MLHPO administration. Maximum 14CO2 expiration appeared 2-4 hr after the dose of LMW compounds. Radioactivity of the upper part of small intestines six hr after the dose of LMW compounds was higher than the values from administered polymer or MLHPO. The remaining radioactivity in the digestive contents and feces 12 hr after administration of LMW compounds was much lower than the values observed from administered polymer or MLHPO. Among internal organs, the liver contained the highest concentration of radioactivities from polymer, MLHPO and LMW fractions, and an especially higher level of radioactivity was found in liver six hr after the administration of LMW compounds. Six hours after the dose of LMW compounds, a relatively higher level of radioactivity also was detected in kidney, brain, heart and lung

  13. 14C-labeled pulegone and metabolites binding to alpha2u-globulin in kidneys of male F-344 rats.

    Ferguson, Ling-Jen Chen; Lebetkin, Edward H; Lih, Fred B; Tomer, Kenneth B; Parkinson, Horace D; Borghoff, Susan J; Burka, Leo T

    2007-09-01

    Pulegone is a major constituent of pennyroyal oil and a minor component of peppermint oil. Pulegone is biotransformed to menthofuran and menthones (diastereomeric menthone and isomenthone) in pennyroyal and peppermint as well as in rodents. Pulegone and menthofuran are hepatotoxic to rodents, and menthones are less toxic. The metabolism and disposition of pulegone and menthofuran were previously studied in rodents, and higher concentrations of pulegone- and menthofuran-derived radioactivity were observed in male than female rat kidney. One explanation is the association of pulegone and metabolites with a male rat-specific protein, alpha2u-globulin. To test this hypothesis, male and female rats were dosed orally with 14C-labeled pulegone (80 mg/kg, 120 microCi/kg) or menthofuran (60 mg/kg, 120 microCi/kg) or menthones (80 mg/kg, 120 microCi/kg) in corn oil, and the kidney cytosol was prepared 24 h after dosing. An equilibrium dialysis experiment showed that in all three studies the radioactivity was associated with kidney cytosol proteins of male but not female rats. The chemicals present in the male rat kidney cytosol after dialysis were extracted with dichloromethane and characterized by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC-MS). All parent compounds were detected, and the metabolites characterized included piperitone from pulegone or menthones treatment, menthones and possibly 8-hydroxymenthones from pulegone treatment, and mintlactones (diastereomeric mintlactone and isomintlactone) and 7a-hydroxymintlactone from menthofuran treatment. Analysis of the male rat kidney cytosol by a gel filtration column demonstrated that the retention was due to reversible binding of these chemicals with the male rat-specific protein alpha2u-globulin. However, binding of pulegone and/or metabolites to alpha2u-globulin did not produce accumulation of this protein in the kidney. PMID:17687727

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

    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.

  15. Metabolism of 14C-labelled glycine, serine, and homoserine in the blue-green alga Synechococcus

    The blue-green alga Synechococcus (Anacystis nidulans, strain L 1402-1) was grown under normal air conditions (0.03 vol% CO2) and with enriched CO2(3.0 vol%) at + 35 0C and relative low light (0.6 x 103 μW/cm2). 14C incorporation after adding 14C-bicarbonate, 14C-aspartate, 14C-glycine, 14C-homoserine and 14C-serine into several products were studied during photosynthesis and in the dark. In high CO2 grown cells a very high initial labelling of aspartate and glycine serine could be observed. Radioactivity of 14C-aspartate was found mainly in glutamate, alanine and threonine. Aspartate, isoleucine and succinate were 14C-labelled after exposure to 14C-homoserine during photosynthesis and in the dark. 14C incorporation into several organic acids (e.g. glyceric acid, malate) and glutamate after feeding 14C-glycine and 14C-serine could be detected during light and dark periods. Results were discussed in respect to the metabolism of amino acids and photosynthetic carboxylation pathways in connection with an interrupted tricarboxylic acid cycle. (author)

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

    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

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

    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

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

    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

  19. 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

    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)

  20. Assessment of the metabolic effects of the ionophore grisorixin on myocardial cells in culture with 14-C-labelled substrates

    Cultures of myocardial cells were utilized to verify the hypothesis that the ionophore grisorixin could facilitate the anaerobic and impair the aerobic metabolism in the myocardium. This was suggested by previous experiments in which the authors found an increase in the cardiac work without increase in the oxygen consumption, while the myocardial uptake of 123-Iodo-hexadecenoic acid was decreased. Tissue cultures were prepared by trypsinization of the myocardium of two to four-day old newborn mice. The cultures were incubated with 14-C-glucose (n=10), 14-C-octanoate (n=14) or 14-C-acetate (n=12). Except for the controls (n=19), they also received 1 μg/ml of an alcoholic solution of grisorixin or 200 μl of 60% alcohol. The cultures were then placed in a circuit with a closed circulation of air which passed through a vibrating reed electrometer for detection of the beta radiations of the 14-CO/sub 2/ liberated by the 14-C labelled substrates. The activity was permanently recorded for measurements of the rate of consumption of these substrates. Compared to the control values, the metabolic rate with grisorixin was significantly decreased for octanoate (77 +- 22 vs 169 +- 62 rho mole/min/mg prot, rho<0.01) and acetate (2.7 +- 1.0 vs 6.0 +- 1.3 rho mole/min/mg prot, rho<0.01). The results for glucose were 1.05 +- 0.24 vs 0.88 +- 0.24 n mole/min/mg prot, (rho<0.10). Alcohol alone produced no significant effect except on the octanoate consumption. These results provide direct evidence that grisorixin favors the anaerobic pathway in the metabolism of the myocardial cells

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

    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)

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

    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.)

  3. Pharmacokinetic studies on 14C-labelled phenanthridine and aromatic diamidine drugs used to control African trypanosomiasis in domestic animals

    For many years ethidium (homidium) bromide (3, 8-diamino-6-phenyl-5-ethyl phenanthridinium bromide) has been used curatively and for limited prophylaxis against Trypanosoma congolense and Trypanosoma vivax infections in ruminants in Africa and aromatic diamidine berenil (diminazeneaceturate, 4, 4'-(diazoamino) benzamidine) has been used as a curative drug against these parasites, but there is little published information about the pharmacokinetics of either drug. Reviewed here is the present knowledge and report results of recent experiments using 14C-labelled drugs to measure blood and tissue fluid levels and tissue residues of ethidium in uninfected and T. congolense-infected laboratory animals and bovines and berenil in laboratory animals. In the case of 14C-ethidium levels of radioactivity in blood and tissue fluids reached a maximum within 1 h of intramuscular injection (1 mg/kg) and then fell rapidly; after 96 h 80-90% of the radioactivity injected had been excreted, approximately one-third in urine and two-thirds in faeces. It is estimated that ca 3-4% of the radioactivity injected is present in tissues of animals sacrificed 9-10 d after administration of drug, the highest residues/unit wet weight of tissue being present in liver and kidney. In similar experiments with 14C-berenil (3.5 mg/kg) radioactivity in blood reached a peak within 30 min, fell rapidly over the next 5 h, but remained at a significant level for 4-6 d. Radioactivity in tissue fluids did not rise as rapidly or to such a high peak level as in blood, but after 2 h remained at approximately twice the level detected in blood for up to 7 d. At 7 d, in marked contrast to ethidium, only 65% of the administered radioactivity had been excreted (44% in urine and 21% in faeces), and in animals sacrificed at that time it was found that the majority (95%) of the residual drug was present in the liver. (author)

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

    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)

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

    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 (convolution sign)Be densities as compared with higher initial (convolution sign)Be densities

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

    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.

  7. Therapeutic effects of low radiation doses

    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

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

    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.

  9. Therapeutic effects of low radiation doses

    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.

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

    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.

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

    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.

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

    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

  13. The effects of gamma irradiation on the fate of hindered phenol antioxidants in food contact polymers. Analytical and 14C-labelling studies

    Allen, David W.; Leathard, David A.; Smith, Christine

    The extractable levels of two hindered phenol antioxidants (Irganox 1076 and Irganox 1010) present in PVC, polyethylene and polypropylene, have been monitored by HPLC techniques following progressive exposure of the polymers to 60Co γ radiation. There is a gradual diminution in the extractable levels of each antioxidant as irradiation progresses as a result of transformation of the antioxidants in the oxidation reactions ensuing during irradiation. Experiments involving the use of a 14C-labelled sample of Irganox 1076 in polyolefins have provided evidence of covalent binding of antioxidant degradation products to the polymer following gamma irradiation. However, there is also evidence of the formation of extractable degradation products, the identity of which is as yet unknown.

  14. The effects of gamma irradiation on the fate of hindered phenol antioxidants in food contact polymers. Analytical and 14C-labelling studies

    The extractable levels of two hindered phenol antioxidants (Irganox 1076 and Irganox 1010) present in PVC, polyethylene and polypropylene have been monitored by HPLC techniques following progressive exposure of the polymers to 60Co(gamma) radiation. There is a gradual diminution in the extractable levels of each antioxidant as irradiation progresses as a result of transformation of the antioxidants in the oxidation reactions ensuing during irradiation. Experiments involving the use of a 14C-labelled sample of Irganox 1076 in polyolefins have provided evidence of covalent binding of antioxidant degradation products to the polymer following gamma irradiation. However, there is also evidence of the formation of extractable degradation products, the identity of which is as yet unknown. (author)

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

    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

  16. An experimental system for the quantitative 14C labelling of whole trees in situ [assimilation chamber, control of CO2 level

    The first part of this paper provides a brief review of the requirements that apply to 14C-labelling chamber technology, particularly for tree labelling, and of the means that can be used to meet them. Two main points are considered: the quality of the plant chamber environment - the necessity of thermal and hygrometric regulations is discussed - and the possibility of determining the exact amount of 14CO2 assimilated by the plant. The authors then describe a simple system allowing the quantitative labelling of entire trees, without temperature- or hygrometry-regulating devices which can be used in the morning. The CO2 concentration is maintained at its natural level throughout the labelling procedure through an injection of cold CO2 operated by an IRGA-driven computer. This system was successfully used for the labelling of grafted walnut trees. (author)

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

    [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.)

  18. Intestinal absorbtion from therapeutic iron doses

    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.)

  19. Mineralization of 14C-labelled aromatic pesticide molecules in Egyptian soils under aerobic and anaerobic conditions

    The mineralization of 2,4-D, carbofuran and pirimiphos-methyl in Egyptian soils was studied over a period of 90 days. Laboratory studies under aerobic and anaerobic conditions were conducted using 14C-ring labelled pesticides. Under anaerobic conditions 10-14% of applied ring labelled 2,4-D mineralized during 90 days with no significant variations due to soil type. Under aerobic conditions, 2,4-D mineralized more readily in clay soil to reach 29-34% of applied dose within 90 days. In clay loam soil, 14C-carbofuran and 14C-pirimiphos-methyl mineralized at a rather slow rate to reach 12-14% and 12-13% of applied dose in 90 days, respectively under aerobic conditions. Generally, soils repeatedly treated with pesticides gave a slightly lower percentage of mineralization than control soils. In all studies, the soil extractable pesticide residues decreased with time and the bound residues gradually increased. The highest binding affinity of about 26-29% was observed with 2,4-D in clay soil under aerobic conditions in 90 days. Carbofuran, and pirimiphos-methyl, on the other hand, had lower binding capacity that did not exceed 16% of applied radioactivity. (author)

  20. High yield synthesis of 14C labelled intermediates of the L-type pentose pathway: octulose mono- and biphosphates, sedoheptulose 1,7-bisphosphate and D-arabinose 5-phosphate

    Methods for the enzymic synthesis, isolation, purification and analysis of the 14C labelled intermediates that are characteristic of the L-type pentose phosphate pathway are described. These are D-glycero D-ido octulose 1,8-bisphosphate and 8-monophosphate; D-glycero D-altro octulose mono- and bisphosphates; sedoheptulose 1,7-bisphosphate and D-arabinose 5-phosphate. The authenticity of each of the 14C-labelled sugar phosphates was confirmed using a variety of chromatographic methods, enzymatic analytic methods and NMR spectroscopy. The 14C labelled compounds are used in investigations involving the search for the identity of the pentose pathway in tissues in vitro, for the measurement of L-type pathway enzyme reactions and for testing the mechanistic predictions of the L-type pathway in vitro. (author)

  1. 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

    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

  2. Decomposition of specifically 14C-labelled phenols and dehydropolymers of coniferyl alcohol as models for lignin degradation by soft and white rot fungi

    Several soft and white rot fungi were compared in their ability to degrade specifically 14C-labelled phenols and dehydropolymers of labelled coniferyl alcohol. Furthermore, plant material which was expected to be specifically labelled in the lignin part was used in the degradation studies. The experiments showed that both groups of fungi were able to release CO2 from methoxyl and carboxyl groups of phenol-carboxylic acids, to degrade side chains of cinnamic acids and cinnamyl alcohols and even to decompose aromatic structures. With the dehydropolymers and the plant material a CO2 release from the methoxyl groups, the side chains and the aromatic carbons was observed. The time dependent course of the CO2 release from these different groups showed in the beginning a higher CO2 evolution from the side chain carbons than from the methoxyl groups, which were later on released to a higher extent. No laccase activity could be detected in the soft rot fungi, and the peroxidase activity was lower than in the white rot fungi. (orig.)

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

    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.)

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

    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

  5. 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.

    Dienel, G A; Nelson, T; Cruz, N F; Jay, T; Crane, A M; Sokoloff, L

    1988-12-25

    Significant dephosphorylation of glucose 6-phosphate due to glucose-6-phosphatase activity in rat brain in vivo was recently reported (Huang, M., and Veech, R.L. (1982) J. Biol. Chem. 257, 11358-11363). 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. PMID:2848837

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

    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

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

    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

  8. [Acetaminophen and the liver: damage at therapeutic dose levels?].

    Petersen, K-U

    2011-12-15

    The possibility of liver intoxication at therapeutic doses of paracetamol (maximal dailydose of 4 x 1 g) is supported by retrospective, but not by controlled prospective studies. Intended orsuicidal overdosages are frequently misjudged in retrospektive reports. Malnutrition, ethanol consumption, and drugs inducing hepatic metabolism are no established riskfactors at therapeutic dose levels. Dose adaptation in existing liver disease is recommended for longer-term use.Transient increases in transaminase values (> 3 x upper limits of normal) after regulardoses of paracetamol are not proof of hepatic damage unless associated with corresponding symptoms or laboratory changes indicative of compromised hepatic function (total bilirubin, INR). There is insufficient evidence of liver injury by paracetamol at regular dose levels. PMID:23964475

  9. Musings: Giftedness, Labeling, and the Non-Therapeutic Dose.

    Gross, Miraca U.M.

    2003-01-01

    This article emphasizes the importance of providing appropriate services to meet the needs of individual gifted students and the need to first diagnose the level of giftedness to administer the right "therapeutic dose." A chart is provided that defines levels of intellectual giftedness by IQ ranges and by prevalence. (Contains 5 references.) (CR)

  10. The therapeutic effect of different dose 131I on hyperthyroidism

    1228 hyperthyroidism patients treated with two doses of 131I 3.7-4.4 MBq/g and 2.59-3.96 MBq/g are observed and the results are compared. The results indicate that the administered dose is larger the treating rate is higher, and hypothyroidation occurs frequently; while the dose is lower, the treating rate and hypothyroidation is also getting lower. So, there are some other factors of the indication selection, the estimation of thyroidism size, individual sensitively and the hyperthyroidism nature history and so on should be considered in the hyperthyroidism therapy for improving the therapeutic effect

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

    Judge Bryan S; James Laura P; Green Jody L; Heard Kennon J; Zolot Liza; Rhyee Sean; Dart Richard C

    2011-01-01

    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 ...

  12. Bremsstrahlung dose of therapeutic beta nuclides in bone and muscle

    Manjunatha, H. C.

    2013-01-01

    In the nuclear medicine, beta nuclides are released during the treatment. This beta interacts with bone and muscle and produces external Bremsstrahlung (EB) radiation. Present work formulated a new method to evaluate the EB spectrum and hence the Bremsstrahlung dose of therapeutic beta nuclides (Lu-177, Sr-90, Sm-153, I-153, Cs-137, Au-201, Dy-165, Mo-99, Sr-89, Fe-59, P-32, Ho-166, Sr-92, Re-188, Y-90, Pr-147, Co-60, K-42) in bone and muscle. The Bremsstrahlung yields of these beta nuclides ...

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

    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.

  14. Radiation doses by therapeutical practices with iodine 131

    The aim of this document is to estimate the doses to workers and public due to therapeutical practices with iodine 131. Environmental and personal doses by external irradiation were determined using thermoluminescent dosimeters (TLD). The environmental dosimetry resulted in an equivalent dose H*(10) of approximately 0,1 mSv. The calculated personal equivalent dose Hp (10) was of the order of 0,1 mSv. The exposition rate was measured, being the values obtained in the range of 0,20 and 0,35 mSv/h. (1m from the abdominal wall). Concentrations of iodine 131 were determinate in the air of the room, during the first day in the hospital. Values obtained were between 0,04 Bq/l and 0,20 Bq/l. Surface samples were taken in the service, obtaining levels of contamination in the range of 0,001 and 0,4 Bq/cm2. The surface samples obtained in the hospital room were about 0,15 Bq/cm2. Urine samples were collected resulting in an eliminated activity of iodine 131, during the first 24 hours, of about 60 % of the administered activity. Samples of sweat of different cutaneous regions were obtained, the maximum values of the activity measured reached 200 Bq/cm2. According to the obtained results it is important to elaborate guides to be given to patients as an instrument to reduce the external exposure and to avoid internal contamination. (author)

  15. Application of capillary gas chromatography-reaction interface/mass spectrometry to the selective detection of 13C-, 15N-, 2H-, and 14C-labeled drugs and their metabolites

    A novel reaction interface/mass spectrometer (RIMS) technique has been applied to the selective detection of 13C-, 15N-, 2H-, and 14C-labeled phenytoin and its metabolites in urine following separation by capillary gas chromatography. The microwave-powered reaction interface converts materials from their original forms into small molecules whose mass spectra serve to identify and quantify the nuclides. The presence of each element is followed by monitoring the isotopic variants of CO2, NO, H2, or CH4 that are produced by the reaction interface. Chromatograms showing only enriched 13C and 15N were produced using the net 13CO2 or 15NO signal derived by subtracting the abundance of naturally occurring isotopes from the observed M + 1 signal. When hydrogen was used as a reactant gas, a selective chromatogram of 2H (D) was obtained by measuring HD at m/Z 3.0219, and a chromatogram showing 14C was obtained by measuring 14CH4 at m/Z 18.034 with a high resolution. For a stable isotope detection, metabolites representing less than 1.5% of the total labeled compounds could be detected in the chromatogram. Detection limits of 170 pCi/mL (34 pCi on column that is equivalent to 187 pg) of a 14C- labeled metabolite was detected. To identify many of these labeled peaks (metabolites), the chromatographic analysis was repeated with the reaction interface turned off and mass spectra obtained at the retention times found in the RIMS experiment. In addition to the ability of GC-RIMS to detect the presence of 13C-, 15N-, and 2H- (D), it can also quantify the level of enrichment. Enrichment of 13C and 15N is quantified by measuring the ratio of excess 13CO2 to total 12CO2 or excess 15NO to total 14NO

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

    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.

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

    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

  18. Profound opiate toxicity in gastroparesis following therapeutic dose.

    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

  19. 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

    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)

  20. Whole-body autoradiographic study on the distribution of pivampicillin-14C labeled at the ampicillin and ester moieties in mice, as compared with those of ampicillin-14C, formaldehyde-14C and pivalic acid-14C

    The distribution of pivampicillin-14C labeled at the phenylglycyl and the oxymethylene moieties and ampicillin-14C were investigated by whole-body autoradiography after oral administration to mice. The distribution of formaldehyde-14C and pivalic acid-14C was also investigated for comparison. The results revealed that, i) pivampicillin is absorbed from intestine much more rapidly and to a larger extent than ampicillin, ii) the distribution pattern was, however, the same for the two drugs, being mainly restricted to the excretory organs such as the liver, kidney, gall and urinary bladders and intestinal tract, and iii) the oxymethylene moiety, the ester group, showed a completely different distribution pattern, being distributed in the bone marrow, pancreas, intestinal mucosa, spleen and thymus; the pattern being the same as that after administration of formaldehyde-14C. It was therefore suggested that pivampicillin is hydrolyzed in vivo to form ampicillin and formaldehyde before entering into the general circulation and that formaldehyde formed is partly incorporated into the general metabolic pathways in the tissues of a rapid cell division or protein synthesis. Pivalic acid, which is to be liverated simultaneously, was shown to be well absorbed, distributed in the bone, kidney, olfactory bulb, salivary gland and some adipose tissues and finally excreted into the urine mostly as its conjugated forms. (author)

  1. Metabolism and excretion kinetics of 14C-labeled and non-labeled difloxacin in pigs after oral administration, and antimicrobial activity of manure containing difloxacin and its metabolites

    Fluoroquinolones are amongst the most important antibiotics used in veterinary medicine. On this account the behavior of difloxacin (DIF) and its metabolites was investigated by administering the 14C-labeled and non-labeled veterinary drug to fattening pigs. The excretion kinetics were determined after daily collection of manure. Sarafloxacin (SAR) was found to be the major metabolite, three further trace metabolites were also recovered, applying high-resolution (HR) mass spectrometric technique. The identification of DIF and SAR was confirmed by comparison with the spectroscopic and chromatographic data of the authentic references. The identification of the three trace metabolites was performed by HR-MS/MS. Only 8.1% of the administered radioactivity remained in the pig after 10 days and DIF accounted for 95.9% of the radioactivity excreted. More than 99% of the labeled compounds were detected and identified in the manure. The mean recoveries for all single electrolytes were ≥94%. Linearity was established over concentration range 10-10,000 μg/kg manure with a correlation coefficient ≥0.99. By using in vitro antimicrobial activity tests against a group of standard pathogenic control strains, the results showed that the residual antibiotic concentrations in the manure of pigs are high enough to exhibit antibacterial activity

  2. Co-permeability of 3H-labeled water and 14C-labeled organic acids across isolated plant cuticles. Investigating cuticular paths of diffusion and predicting cuticular transpiration

    Penetration of 3H-labeled water (3H2O) and the 14C-labeled organic acids benzoic acid ([14C]BA), salicylic acid ([14C]SA), and 2,4-dichlorophenoxyacetic acid ([14C]2,4-D) were measured simultaneously in isolated cuticular membranes of Prunus laurocerasus L., Ginkgo biloba L., and Juglans regia L. For each of the three pairs of compounds (3H2O/[14C]BA, 3H2O/[14C]SA, and 3H2O/[14C]2,4-D) rates of cuticular water penetration were highly correlated with the rates of penetration of the organic acids. Therefore, water and organic acids penetrated the cuticles by the same routes. With the combination 3H2O/[14C]BA, co-permeability was measured with isolated cuticles of nine other plant species. Permeances of 3H2O of all 12 investigated species were highly correlated with the permeances of [14C]BA (r2 = 0.95). Thus, cuticular transpiration can be predicted from BA permeance. The application of this experimental method, together with the established prediction equation, offers the opportunity to answer several important questions about cuticular transport physiology in future investigations

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

    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)

  4. EFFECT OF THERAPEUTIC AND DOUBLE THERAPEUTIC DOSES OF IVERMECTIN ON OXIDATIVE STATUS AND REPRODUCTIVE HORMONES IN MALE RABBITS

    Ali Hafez El-Far

    2013-01-01

    To investigate the biochemical alterations of oxidative status and male sexual hormones, thyroid hormones, cortisol, liver function and kidney function; sixty male New Zealand White rabbits were equally allotted according to their body weight into two groups. Control samples were collected before subcutaneous injection of rabbits by ivermectinin Therapeutic (TD) and Double Therapeutic Doses (DTD). After injection blood samples were collected from ear vein at 1st, 3rd and 7th day of experiment...

  5. Occupational and patient doses in the therapeutic cave, Tapolca (Hungary)

    The radon concentration has been measured for three years in a hospital cave used for medical treatment of respiratory diseases. A mean value of the actual equilibrium factor measured in the cave in different seasons was used, different from the commonly used 0.4. The dose contribution to the patients and the staff was calculated using these data. The results of the dose assessment show that the staff in the hospital cave can receive doses up to the dose limit for occupational exposure (20 mSv y-1) when working 4 h per day in the cave. Patients receive 0.18-4.22 mSv committed effective dose during the treatment period depending on the exposure periods. The only solution to reduce the dose to the staff seems to be decreasing the time they spend underground, because intensive ventilation would disturb the special microclimate of the cave. (author)

  6. Specification of absorbed dose for reporting a therapeutic irradiation

    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. A convenient photosynthesis of uniformly [14C]-labelled D-glucose, D-fructose and sucrose, and chemical synthesis of methyl-α-D-glucopyranoside ([U-14C]-glucose)

    This paper describes a convenient procedure for the radiochemical preparation of D-[U-14C]-glucose, D-[U-14C]-fructose and [U-14C]-sucrose with high specific activity by photosynthesis using ‘canna indica’ leaf, [14C]-carbon dioxide and water in presence of light in a closed system. The [14C]-sugars formed were extracted, separated and then purified by paper chromatography. Further, the pure D-[U-14C]-glucose obtained was converted to methyl-α-D-glucopyranoside ([U-14C]-glucose) by glycosidation with methanol using (i) HCl, the conventional Fischer method (ii) heterogeneous organic cation exchange resin (Amberlite IR-120 (H+)) and (iii) heterogeneous inorganic cation exchanged montmorillonites called metal M+n-monts. The results indicated that the latter in the form of Fe+3-montmorillonite gave a better yield ( 65%) as compared to others (40–56%). The radiochemical purity of the no-carrier added product was more than 98%. The product retained its specific activity as that of the starting material which is in the range of 250–300 mCi/mmole (9.25–11.1 GBq/mmole), suitable for use as a radiotracer in biochemical investigations. - Graphical abstract: A convenient photosynthesis of uniformly [14C]-labelled D-glucose, D-fructose and sucrose, and chemical synthesis of methyl-α-D-glucopyranoside ([U-14C]-glucose)/[14C]–AMG, in short. The photosynthesis of D-[U-14C]-glucose, and two other [14C]-sugars (fructose and sucrose) with high specific activity using ‘Canna indica’ leaf, 14CO2 and water in presence of light is presented in this paper. Further, the D-[U-14C]-glucose obtained was converted to methyl-α-D-glucopyranoside ([U-14C]-glucose)/[14C]–AMG having 98% radiochemical purity and specific activity in the range of 250–300 mCi/mmole, using montmorillonites (M+n-monts). Highlights: ► Synthesis of methyl α D-glucopyranoside ([U-14C] glucose) has not been reported using M+n-monts. ► M+n-monts are reusable, economical, environmentally benign

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

    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...

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

    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 the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians’ or patients’ choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels

  10. Methodology to administer therapeutic dose of I-131

    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. Measurement of dose distributions using film in therapeutic electron beams

    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

  12. The therapeutic effect of high-dose esomeprazole on stress ulcer bleeding in trauma patients

    Cui Lihong; Li Chao; Wang Xiaohui; Yan Zhihui; He Xing; Gong Sandong

    2015-01-01

    Purpose: To compare the therapeutic effects of different doses of intravenous esomeprazole on treating trauma patients with stress ulcer bleeding. Methods: A total of 102 trauma patients with stress ulcer bleeding were randomly divided into 2 groups: 52 patients were assigned to the high-dose group who received 80 mg intravenous esomeprazole, and then 8 mg/h continuous infusion for 3 days; 50 patients were assigned to the conventional dose group who received 40 mg intravenous esomeprazole ...

  13. Radiosterilisation of the vagina in therapeutic doses - does it exist

    The endogenous genital flora is a major source of infections of the female genital tract, especially in patients with cervical or endometrial cancer. Until recently the 'radiosterilisation of the vagina', respectively a prophylactic and/or therapeutic effect of irradiation (external highvoltage as well as intracavitary-radium) concerning infections was postulated in the literature. This theory was disproved in a prospective clinical and bacteriological study covering 48 patients with advanced cervical cancer undergoing primary intracavitary radium-irradiation and 38 patients with inoperable endometrical cancer, undergoing primary iridium-192-afterloading. Following intracavitary radium for cervical cancer some typical nosocomial pathogens like Streptococcus faecalis, Enterobacter, Klebsiella, Proteus and Pseudomonas were isolated significantly more frequently than before treatment. Likewise, the mean number of aerobic bacterial species increased significantly after irradiation. Also primary Ir-192 (afterloading) irradiation did not alter the frequency of isolation of the resident flora in endometrial cancer patients. Therefore, 'radiosterilisation' of the vagina as result of radiotherapy does not exist. (orig.)

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

    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

  15. ANTI-HYPERGLYCEMIC ACTIVITY OF SIMVASTATIN ALONE (THERAPEUTIC DOSE) AND COMBINATION OF SIMVASTATIN AND GLIPIZIDE (SUB THERAPEUTIC DOSES) ON ALLOXAN INDUCED HYPERGLYCEMIA IN ALBINO RATS

    V.S. Harish Kumar*, N.R. Sindhu, Rajashri S. Patil and Umakant Patil

    2012-01-01

    The present study was designed to evaluate anti-hyperglycemic activity of simvastatin alone and the combination of sub therapeutic doses of simvastatin and glipizide. Hyperglycemia was induced experimentally in albino rats by subcutaneous injection of alloxan in a dose of 175 mg/kg body weight. After 72 hours of alloxan treatment, rats showing hyperglycemia (blood glucose level of 400 mg/dl and above) were included in the study. They were divided into four groups of 6 animals each (n=24). Ora...

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

    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.

  17. ANTI-HYPERGLYCEMIC ACTIVITY OF SIMVASTATIN ALONE (THERAPEUTIC DOSE AND COMBINATION OF SIMVASTATIN AND GLIPIZIDE (SUB THERAPEUTIC DOSES ON ALLOXAN INDUCED HYPERGLYCEMIA IN ALBINO RATS

    V.S. Harish Kumar*, N.R. Sindhu, Rajashri S. Patil and Umakant Patil

    2012-11-01

    Full Text Available The present study was designed to evaluate anti-hyperglycemic activity of simvastatin alone and the combination of sub therapeutic doses of simvastatin and glipizide. Hyperglycemia was induced experimentally in albino rats by subcutaneous injection of alloxan in a dose of 175 mg/kg body weight. After 72 hours of alloxan treatment, rats showing hyperglycemia (blood glucose level of 400 mg/dl and above were included in the study. They were divided into four groups of 6 animals each (n=24. Oral administration of normal saline 0.5 ml, glipizide 2.5 mg/kg body weight, simvastatin 10 mg/kg body weight and sub therapeutic doses of both test (simvastatin 5 mg/kg body weight and standard (glipizide 1.25 mg/kg body weight drugs, was done respectively into each of the four groups for 30 consecutive days in order to assess the effect in terms of reduction in blood glucose level. Blood glucose was estimated on 0th, 10th, 20th, and 30th days of study in fixed time intervals. In the test group, there was a gradual fall in the blood glucose level which reached up to 308.3 mg/dl by 30th day of study (P < 0.001. In case of combination of sub therapeutic doses of simvastatin and glipizide, the fall in blood glucose level was gradual and sustained and it reached up to 201.5 mg/dl by the 30th day (P < 0.001. These observations are comparable with the results obtained in case of glipizide treated rats, the standard group. Simvastatin appreciably lowered the blood glucose level, but the combination of sub therapeutic doses of simvastatin and glipizide, by virtue of their possible synergistic effect produced further reduction in the blood glucose level. This study provides evidence in support of a potential anti-hyperglycemic effect of simvastatin and its combination with glipizide. Thus the combined treatment of simvastatin and glipzide may have added benefit for the diabetic patients associated with hyperlipidemia.

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

    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.

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

    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.)

  20. Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

    In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease. (author)

  1. Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes.

    Saif, M Wasif; Choma, Adrienne; Salamone, Salvatore J; Chu, Edward

    2009-11-18

    Chemotherapy dosing of the fluoropyrimidine 5-fluorouracil (5-FU) is currently based on body surface area. However, body surface area-based dosing has been associated with clinically significant pharmacokinetic variability, and as such, dosing based on body surface area may be of limited use. The clinical activity of 5-FU is modest at standard doses, and in general, dosing is limited by the safety profile, with myelosuppression and gastrointestinal toxicity being the most commonly observed side effects. Various strategies have been developed to enhance the clinical activity of 5-FU, such as biochemical modulation, alterations in scheduling of administration, and the use of oral chemotherapy. Studies that have shown an association between plasma concentration with toxicity and clinical efficacy have shown that pharmacokinetically guided dose adjustments can substantially improve the therapeutic index of 5-FU treatment. These studies have shown that only 20%-30% of patients treated with a 5-FU-based regimen have 5-FU levels that are in the appropriate therapeutic range--approximately 40%-60% of patients are underdosed and 10%-20% of patients are overdosed. To date, 5-FU drug testing has not been widely used because of the lack of a simple, fast, and inexpensive method. Recent advances in testing based on liquid chromatography-mass spectroscopy and a nanoparticle antibody-based immunoassay for 5-FU may now allow for routine monitoring of 5-FU in clinical practice. We review the data on pharmacokinetically guided dose adjustment of 5-FU and discuss the potential of this approach to advance therapeutic outcomes. PMID:19841331

  2. The therapeutic effect of high-dose esomeprazole on stress ulcer bleeding in trauma patients

    Cui Lihong

    2015-07-01

    Full Text Available Purpose: To compare the therapeutic effects of different doses of intravenous esomeprazole on treating trauma patients with stress ulcer bleeding. Methods: A total of 102 trauma patients with stress ulcer bleeding were randomly divided into 2 groups: 52 patients were assigned to the high-dose group who received 80 mg intravenous esomeprazole, and then 8 mg/h continuous infusion for 3 days; 50 patients were assigned to the conventional dose group who received 40 mg intravenous esomeprazole sodium once every 12 h for 72 h. Results: Compared with the conventional dose group, the total efficiency of the high-dose group and conventional dose group was 98.08% and 86.00%, respectively (p < 0.05, the hemostatic time was 22.10 h ± 5.18 h and 28.27 h ± 5.96 h, respectively (p < 0.05. Conclusion: Both doses of intravenous esomeprazole have good hemostatic effects on stress ulcer bleeding in trauma patients. The high-dose esomeprazole is better for hemostasis.

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

    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

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

    [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.

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

    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.

  6. Health risks associated with low dose diagnostic or therapeutic radiation exposures

    The health risks to humans associated with exposure to low doses of ionizing radiation have been extrapolated from effects observed at high doses, dose rates, and mixed radiation qualities using a linear no threshold model. Based on this approach, it has been argued that human exposure to low doses of diagnostics X-rays and gamma-rays increase an individual's risk of developing cancer throughout their life-time. Also, repeated medical diagnostic procedures involving low dose exposures will have an additive effect and consequently further increase health risk. The specific aim of this seminar will be to address the relative risk associated with diagnostic X-rays from CT scans and gamma-rays from positron emission tomography (PET) scans. Objectives of the talk will include: 1) Defining low dose exposures at a cellular level and relate that to diagnostic or therapeutic exposures, 2) Describing modern tools in molecular cytogenetics to estimate radiation exposure and assess radiation risk, 3) Identifying the different cellular mechanisms that influence radiation risk at high and low dose exposures and relate that to individual radiation risk. (author)

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

    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.

  8. Radiation exposure to examiners and patients during therapeutic ERCP: Dose optimisation and risk estimation

    Aim: This study intended to optimise the radiation dose during therapeutic ERCP, and to estimate the risk for examiners and patients, to compare the doses based on available data obtained by other researchers and reference levels recommended by international organizations, and to evaluate the technique applied in order to reduce patient and examiners doses. Materials and Methods: 153 patients were studied in two Gastroenterology Departments, (group A, 111; group B, 42). Thermoluminescent dosimeters (TLD) were used to measure the staff and patients entrance surface dose (ESD) at different body sites. Results: The mean ESD, exit and thyroid surface dose per procedure was estimated to be 68.75 mGy, 3.45 mGy and 0.67 mGy, respectively. The mean patient effective dose was 3.44 mSv, and the cancer risk per procedure was estimated to be 190 x10-6. The effective dose for the first, second and third examiner was 0.4 μSv, 0.2 μSv and 5.0 μSv, respectively. Conclusion: The patient dose can be optimized by the presence of two experienced examiners and reduction of radiographic images. The examiners should use a wrap around lead apron since the highest dose originating from the X-ray tube, is incident on their side and back. The current formulae, which exist, underestimate the effective dose to the examiners, when they are applied for ERCP procedures. For both patients and examiners, our results were up to 60% lower compared to the lowest values found in previous studies. (authors)

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

    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.

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

    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

  11. Antigen dose escalation study of a VEGF-based therapeutic cancer vaccine in non human primates.

    Morera, Yanelys; Bequet-Romero, Mónica; Ayala, Marta; Pérez, Pedro Puente; Castro, Jorge; Sánchez, Javier; Alba, José Suárez; Ancízar, Julio; Cosme, Karelia; Gavilondo, Jorge V

    2012-01-01

    CIGB-247 is a cancer therapeutic, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the oil free adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). Our previous experimental studies in mice with CIGB-247 have shown that the vaccine has both anti-tumoral and anti-metastatic activity, and produces both antibodies that block VEGF-VEGF receptor interaction, and a specific T-cell cytotoxic response against tumor cells. CIGB-247, with an antigen dose of 100 μg, has been characterized by an excellent safety profile in mice, rats, rabbits, and non human primates. In this article we extend the immunogenicity and safety studies of CIGB-247 in non human primates, scaling the antigen dose from 100 μg to 200 and 400 μg/vaccination. Our results indicate that such dose escalation did not affect animal behavior, clinical status, and blood parameters and biochemistry. Also, vaccination did not interfere with skin deep skin wound healing. Anti-VEGF IgG antibodies and specific T-cell mediated responses were documented at all three studied doses. Antigen dose apparently did not determine differences in maximum antibody titer during the 8 weekly immunization induction phase, or the subsequent increase in antibodies seen for monthly boosters delivered afterwards. Higher antigen doses had a positive influence in antibody titer maintenance, after cessation of immunizations. Boosters were important to achieve maximum antibody VEGF blocking activity, and specific T-cell responses in all individuals. Purified IgG from CIGB-247 immunized monkey sera was able to impair proliferation and formation of capillary-like structures in Matrigel, for HMEC cells in culture. Altogether, these results support the further clinical development of the CIGB-247 therapeutic cancer vaccine, and inform on the potential mechanisms involved in its effect. PMID:22075086

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

    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

  13. The therapeutic effects and absorbed dose of I-131 MIBG in patients with malignant pheochromocytoma

    High selective tumor uptake and retention of I-131 MIBG (MIBG) is known as a prerequisite for successful treatment of pheochromocytoma. We evaluated the relationship of absorbed dose of MIBG in tumor and therapeutic effects in twelve selected patients gained over a period of more than 5 years. All patients were diagnosed as malignant adrenal or extra-adrenal pheochromocytoma clinically. The metastases were identified in 10 patients on tracer dose images prior to therapy. Except for 4 patients, all others were symptomatic and had raised hormones indicative of tumor hyper-secretion at the time of enrolment. The number of doses of MIBG ranged from 1 to 3 times with 3.7 GBq per course and a cumulative activity from 3.7 to 11.1 GBq. The estimation of the therapeutic MIBG absorbed dose was performed on the basis of measurement after a therapy by using SPECT on day 1,3,and 5. The absorbed dose was calculated from MIRD data. None of the patients had a complete remission to I-131 MIBG therapy. In one patient, died with DIC 4 months after therapy. Of the 11 patients evaluated, a partial remission (PR) and stable disease was observed in one case individually. A dramatic improvement of the symptoms was noticed in this PR patient and maintained well condition now, 12.0 years after initial MIBG therapy. The cumulated absorbed dose with 11.1 GBq of MIBG calculated in lung and lymph node metastases was exceeded over 150Gy. MIBG uptake in each tumor was thought to be homogeneous. The other nine patients, however, showed little effects, and five were died with disease in 2.6 to 4.1 years after therapy. MIBG therapy is an effective palliative treatment for malignant pheochromocytoma, although a complete tumor response rate is low. It is sufficient in the therapy of these difficult tumors that response of tumors is partial remission or the tumor arrest. Criteria of patient selection with therapeutic modalities should be estimated including the absorbed dose and also the distribution

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

    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

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

    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.

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

    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.

  17. Therapeutic drug monitoring to adjust dosing in morbid obesity - a new use for an old methodology.

    Martin, Jennifer H; Saleem, Mohamed; Looke, David

    2012-05-01

    The phenomena of hunger and need at one end of the spectrum and obesity and plenty on the other is an anomaly of the 21(st) century, likely to be due to a combination of distributive inequities in food, social justice, access to education and other socio-economic factors. Both are major problems worldwide, although obesity has more media coverage due to the exponentially increasing incidence and the huge social and economic burden this is placing on Western society. For example, prevalence rates of obesity are currently exceeding 30% of adults in the USA with direct morbidity and mortality complications, in addition to the additional obesity-related health problems and death. Obesity is also rising in children. Obese people are thus a sizable group, and as with those with altered renal or liver function, require specific consideration with respect to the appropriate dosing of medications. However guidelines for how to do this in obesity are not currently available, due to the paucity of literature and regulatory rules for new medications which usually only request the demonstration of average population effectiveness. We believe it is timely for regulatory agencies worldwide to mandate studies involving consideration of body size, particularly obesity, in approving new medications across the therapeutic spectrum. This will drive the pharmaceutical industry to consider these groups in studies and will encourage investigator-initiated research using therapeutic drug monitoring (TDM), target concentration therapy (TCI) and pharmacogenetic (PGx) studies to optimize drug dosing. PMID:22129454

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

    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)

  19. Population pharmacokinetics of piperacillin in the early phase of septic shock – does standard dosing result in therapeutic plasma concentrations?

    Öbrink-Hansen, Kristina Margareta; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

    2015-01-01

    Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic variability seen in this patient population. Piperacillin/tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we...... determined the pharmacokinetic profile of piperacillin (4 g) every 8 hours, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of...... bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug need to be considered....

  20. Research on relationship between dose per fraction and therapeutic effect in fractionated radiotherapy with a tumor control probability model

    Objective: To study whether the effect can be improved by using unequal dose per fraction in fractionated radiotherapy with the given overall treatment dose and time. Methods: Referring to the calculating formula of cell surviving probability, a new tumor control probability (TCP) calculating model following the fractionated radiotherapy has been set up. Then with four assumed fractionated dose protocols (fractionated dose increase or decrease in a week or in the whole treatment time), the TCP value will be calculated with the calculation model to get the relationship curves of some interested variables. Results: The calculation results show that the four assumed unequal fractionated dose (UEFD) protocols were better than the conventional equal fractionated dose (EFD) protocol. The more uneven fractionated dose distribution was the better TCP results would be. Conclusion: Given the overall treatment dose and time, treatment with UFED protocols can get better therapeutic effect than treatment with EFD protocol theoretically

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

    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

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

    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

  3. Synthesis of 3H and 14C labelled changrolin

    3 kinds of [14C] and [3H] changrolin labelled at different positions (I, II, III) were prepared. The synthesis of I is as follows: (Scheme 1): Heating 5-bromoanthranilic acid with formamide yielded IV, which on heating with POCl3 gave V. Condensation of V with 4-aminophenol and Mannich reaction produced 6-bromochangrolin (VI). Catalytic dehalogenation of VI with tritium gas gave I. The synthesis of II was started from (14C) formamide and anthranilic acid. Labelled 4-chloroquine obtained was condensed with Mannich base (VII) directly (Scheme 2). III was prepared by 1 step with (14C) formaldehyde (Scheme 1)

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

    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)

  5. Therapeutic application of IL-4 on total body irradiated mice with lethal doses

    In the present study, we determined the consequences of IL-4 treatment on survival hematopoietic recovery as well as acute inflammatory response of irradiated mice. Mice were total body irradiated with lethal doses of γ-rays and treated with IL-4 30 min or 2 h after exposure. Our data show an enhancement of the 30-day survival after 8 Gy irradiation, from 20% for placebo-treated mice to 75% with IL-4. It is generally admitted that the death of animals occurring in this dose range is due to hematopoietic syndrome. Therefore, we determined the efficacy of IL-4 on promoting the recovery of blood cell counts and progenitors in bone marrow. The hematopoietic status of animals is the same whether or not treated with IL-4. Given the anti-inflammatory properties of IL-4, we studied the consequences of IL-4 treatment on the inflammatory response within 24 h after 8 Gy exposure. We have shown that IL-4 treatment led to a limitation of the release of inflammatory mediators, such as IL-1β or KC, in the plasma or tissues of irradiated mice. On the other hand, IL-4 improved the ratio-induced metabolic and functional damages in the central nervous system. In conclusion, our results have shown an enhanced survival of IL-4 treated irradiated mice without improvement of hematopoietic reconstitution. Therapeutic potential of IL-4 could result, at least in part, from the limitation of the radio-induced inflammatory response. (author)

  6. Low dose radiation increased the therapeutic efficacy of cyclophosphamide on S180 sarcoma bearing mice

    We examined whether low dose radiation (LDR) exposure (75 mGy) could increase the therapeutic efficacy of cyclophosphamide (CTX) by comparing the effects of tumor suppression, tumor cell apoptosis, cell cycle and proliferation of bone marrow in vivo. Kunming mice implanted with S180 sarcoma cells were given 75 mGy whole body γ-ray radiation exposure and CTX (300 mg/kg) by intraperitoneal injection 36 hours after LDR. Proliferation of bone marrow and tumor cells was analyzed by flow cytometry. Cytochrome c leakage from the tumor was measured by Western-blot. We discovered that tumor growth was significantly reduced in the group exposed to CTX add to LDR. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G1 phase in the groups treated with CTX and CTX+LDR, but cell cycle was more significantly arrested in mice exposed to LDR followed by CTX than in mice exposed only to LDR or CTX chemotherapy. Concentration of bone marrow cells and proliferation index in CTX+LDR mice were higher than those in the untreated mice. LDR or CTX+LDR could induce greater cytochrome c levels and caspase-3 activity in tumors. These results suggest that low dose radiation can enhance the anti-tumor effect of the chemotherapy agent CTX markedly. Furthermore, LDR significantly protects hematopoetic function of the bone marrow, which is of practical significance on adjuvant chemotherapy. (author)

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

    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)

  8. Synthesis of 14C-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

    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. 14C-RDX was prepared by nitration of hexamethylenetetramine (HMTA) according to the Hale process. 14C-ring and methyl labelled TNTs synthesized according to the Dorey and Carper procedure. 14C-cellulose was synthesized from 14C-glucose by Acetobacter xylinum. Nitration of the 14C-cellulose yielded 14C-nitrocellulose. 14C-glycidyl azide polymer was obtained by polymerization and azidation of 14C-epichlorohydrin (ECH) which was synthesized from 14C-glycerol. Hydrochlorination of 14C-glycerol and epoxidation of the resulting 14C-1,3-dichloro 2-propanol yielded 14C-ECH. The syntheses of these 14C-labelled explosives are described in this paper. (Author)

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

    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)

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

    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

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

    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

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

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

    2009-09-15

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

  13. Effect of therapeutic doses of enrofloxacin on circulating lymphocyte subpopulations in pigs

    Pomorska-Mól Małgorzata

    2015-06-01

    Full Text Available Twenty pigs of similar genetics (PIC were used. Pigs were randomly divided into two groups: experimental (ENRO, n = 10 and control (C, n = 10. From day 0 to day 4, pigs from ENRO group received enrofloxacin at the recommended therapeutic dose. Pigs from C group received PBS instead of enrofloxacin. Blood samples were collected on days 0 (before antibiotic administration, 2, 4 (during antibiotic therapy, 9, and 13 of the study (after enrofloxacin administration. Haematological examination and flow cytometry were used to establish the relative and absolute counts of various leukocyte subsets. Lymphocyte subpopulations were measured by fluorochrom-labelled antibodies according to following definitions: CD3+ (T cells, CD21+ (B cells, CD4+CD8- (helper T cells, Th, CD4-CD8+ (cytolytic T cells, CLT, CD4+CD8+ (cytolytic and memory T cells. The present study revealed the modulating effect of enrofloxacin on the composition of circulating lymphocytes in pigs. Concentration and percentage of CD8+ cells decreased significantly after treatment with enrofloxacin and as a result the absolute CD4/CD8 ratio increased significantly as compared to control group (P < 0.05.These findings should prompt further studies on the practical significance of the results obtained in terms of clinical implications. In view of the results, it cannot be excluded that enrofloxacin may also have immunomodulatory effects on host response to infection.

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

    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

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

    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.)

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

    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

  17. Improvement of radioactive concentration of 131I produced by dry distillation technique for use in high dose therapeutic capsules

    Radioiodine 131I-NaI in high radioactive concentration of 131I is preferred for the preparation of high dose therapeutic capsules. Natural Tellurium Dioxide irradiated in Dhruva reactor and 131I separated by dry distillation technique and trapped in alkaline sodium sulfite solution. Change in molarity of sodium hydroxide from 1 mM to 13 mM at a particular timing of 30 min after distillation starting time improves radioactive concentration of 131I without affecting the radiochemical purity of the product 131I-NaI. Thus increase in radioactive concentration of 131I from 1.89±0.37 Ci/ml to 3.27±0.52 Ci/ml achieved making the product 131I-NaI useful for formulation of high dose therapeutic capsule. (author)

  18. Therapeutic treatment plan optimization with probability density-based dose prescription

    The dose optimization in inverse planning is realized under the guidance of an objective function. The prescription doses in a conventional approach are usually rigid values, defining in most instances an ill-conditioned optimization problem. In this work, we propose a more general dose optimization scheme based on a statistical formalism [Xing et al., Med. Phys. 21, 2348-2358 (1999)]. Instead of a rigid dose, the prescription to a structure is specified by a preference function, which describes the user's preference over other doses in case the most desired dose is not attainable. The variation range of the prescription dose and the shape of the preference function are predesigned by the user based on prior clinical experience. Consequently, during the iterative optimization process, the prescription dose is allowed to deviate, with a certain preference level, from the most desired dose. By not restricting the prescription dose to a fixed value, the optimization problem becomes less ill-defined. The conventional inverse planning algorithm represents a special case of the new formalism. An iterative dose optimization algorithm is used to optimize the system. The performance of the proposed technique is systematically studied using a hypothetical C-shaped tumor with an abutting circular critical structure and a prostate case. It is shown that the final dose distribution can be manipulated flexibly by tuning the shape of the preference function and that using a preference function can lead to optimized dose distributions in accordance with the planner's specification. The proposed framework offers an effective mechanism to formalize the planner's priorities over different possible clinical scenarios and incorporate them into dose optimization. The enhanced control over the final plan may greatly facilitate the IMRT treatment planning process

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

    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

  20. New method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. Clinical and hormonal studies

    Gronroos, M.; Turunen, T.; Raekallio, J.; Ruotsalinen, P.; Salmi, T. (Turku Univ. (Finland). Dept. of Obstetrics and Gynecology)

    1982-08-01

    The authors present a new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. The problem with this method has been how to inactivate the endometrium while maintaining the physiological function of the ovaries. In 5/29 young patients regular or irregular bleedings occurred after an endometrial dose of 11+-1 Gy. These subjects were given a repeat low dose intrauterine irradiation. Thereafter no bleedings were found in four out of five patients. Two to 9 years after the repeat irradiation the plasma levels of E/sub 1/, E/sub 2/, FSH and LH corresponded closely to those of healthy women in reproductive age in three out of five patients; some high plasma P levels indicated ovulation. In two patients the E/sub 1/, E/sub 2/, and P values were more likely postmenopausal but, on the other hand, FSH and LH values reproductive ones. 19 refs.

  1. A new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. Clinical and hormonal studies

    The authors present a new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. The problem with this method has been how to inactivate the endometrium while maintaining the physiological function of the ovaries. In 5/29 young patients regular or irregular bleedings occurred after an endometrial dose of 11+-1 Gy. These subjects were given a repeat low dose intrauterine irradiation. Thereafter no bleedings were found in four out of five patients. Two to 9 years after the repeat irradiation the plasma levels of E1, E2, FSH and LH corresponded closely to those of healthy women in reproductive age in three out of five patients; some high plasma P levels indicated ovulation. In two patients the E1, E2, and P values were more likely postmenopausal but, on the other hand, FSH and LH values reproductive ones. (author)

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

    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

  3. External radiation doses in a household from a patient receiving a therapeutic amount of 131I

    Gamma-ray measurements were carried out during a 4-week period in a household to determine the external dose to family members from a patient who was being treated for hyperthyroidism with the administration of 220 MBq of 131I. The measured doses in air were 0.08 and 0.09 mGy for the children and 0.49 mGy for the spouse. The doses delivered at various locations within the house, the breakdown for various activities of family member, and the potential doses for other scenarios are also given. Based on these results and those of past studies, doses to individuals from such therapy are seen to be generally higher than the annual limits set for members of the general public for nuclear facility higher than the annual limits set for members of the general public for nuclear facility operations in the US and, and in certain situations, doses could even exceed 5 mGy for some family members. In terms of collective dose, this source of exposure is estimated to be about the same as the contribution from the nuclear fuel cycle and equivalent to or larger than other environmental sources, such as luminous timepieces, smoke detectors, thorium gas mantles, dental prostheses, welding rods, and opthalmic glass

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

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

    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

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

    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

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

    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.

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

    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.

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

    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.

  10. Comparison of therapeutic effect of low-dose low-molecular-weight heparin (enoxaparin vs. oral prednisone in treatment of patients with lichen planus; A clinical trial

    Fariba Iraji

    2013-01-01

    Conclusion: Low dose enoxaparin on lichen Planus have therapeutic effect and is important for the least side effects but not as much as oral prednisone. But it could be accepted as an alternative treatment.

  11. Exit Dose Measurement in Therapeutic High Energy Photon Beams and Cobalt-60 Gamma Rays

    Sathiyan, S.; Ravikumar, M.

    2007-01-01

    To estimate the skin dose to the patient from the treatment planning, the knowledge about exit dose is essential, which is calculated from the percentage depth dose. In this study 6 MV and 18 MV beams from linear accelerator and cobalt-60 beams were used. The ionometric measurements were carried out with parallel plate chamber of sensitive volume 0.16 cc. Parallel plate chamber was fitted in to 30 x 30 cm2 polystyrene phantom at a fixed FSD with the measuring entrance window facing farther from the source. The field size for this measuring condition was maintained at 10 x 10 cm2. The ionization measurements were also carried out by changing the thickness of the polystyrene phantom at the entrance side of the point of measurement. In order to find out the variation of relative exit dose (RED) with field size the measurements were carried out without and with the full back-scattering material (27.2 gm/cm2) placed beyond the entrance window of the chamber. The measurements were also done for the entrance polystyrene phantom thicknesses of 10, 20 and 30 cm for the field size ranging from 5 x 5 cm2 to 30 x 30 cm2. The dose at the exit surface with no backscatter material is about 4.4%, 3.7% and 5.8% less than the dose with the full backscatter material present beyond the point of measurement for 6 MV, 18 MV X-rays and cobalt-60 gamma rays. The reduction in exit dose does not depend much of the phantom thickness through which the beam traverses before exiting at the chamber side. Dose enhancements of about 1.03 times were observed for a field size of 5 x 5 cm2 for 6 MV, 18 MV X-rays and cobalt-60 gamma rays. The dose enhancement factor (DEF) values were noticed to vary with field size beyond 15 x 15 cm2 for all the energies studied. Also it can be observed that the dose enhancement factor (DEF) values do not depend on the thickness of the phantom material through which the beam has traversed. The DEF values were found to vary marginally for different phantom material

  12. External dose measurements for patients receiving therapeutic I-131 for thyroid cancer

    Iodine-131 is a well established and effective treatment, supplementing surgery, in differentiated thyroid carcinoma. Iodine-131 except from its β-emission, that generates a cell-killing effect in a small area, has also a γ-emission irradiating distant tissues and even people who are close enough with the treated patient. The International Commission on Radiation Protection, ICRP has estimated the probability of a radiation-induced fatal cancer for the whole population at 5.0 % per sievert for low doses and at low dose rates and at 1.3 % for serious genetic diseases. For elderly people the probability seems to be 3 to 10 times lower, whereas for children up to the age of 10 years, 2-3 times higher. These findings led the ICRP to recommend new dose limits, lower than the previous ones. The European Union has endorsed the ICRP recommendations and the Council issued two directives, with which the Greek legislation complied recently. The current annual public dose limit is 1 mSv, while in the new Greek legislation the concept of dose constrains (0.5 m Sv in Greece) has also been proposed as a goal to reach whenever possible

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

    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.

  14. Lyoluminescence dosimetry for therapeutic dose range. State-of-the-art

    Lyoluminescence, i.e. emission of light on dissolution by previously irradiated solid has been applied to the needs of radiation dosimetry. Saccharides and amino acids are the most suitable dosimetric materials for the range of doses encountered in radiation therapy. These materials are tissue equivalent for X-rays, gamma rays, electrons, neutrons and even pi-mesons. Commercial read-out equipment is available now and in the dose range 0.1 - 20 Gy a reproducibility of 1 - 2.5 % can be achieved with commercially available dosimetric materials

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

    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

  16. Contamination dose from photoneutron processes in bodily tissues during therapeutic radiation delivery

    Dose to the total body from induced radiation resulting from primary exposure to radiotherapeutic beams is not detailed in routine treatment planning though this information is potentially important for better estimates of health risks including secondary cancers. This information can also allow better management of patient treatment logistics, suggesting better timing, sequencing, and conduct of treatment. Monte Carlo simulations capable of taking into account all interactions contributing to the dose to the total body, including neutron scattering and induced radioactivity, provide the most versatile and accurate tool for investigating these effects. MCNPX code version 2.2.6 with full IAEA library of photoneutron cross sections is particularly suited to trace not only photoneutrons but also protons and heavy ion particles that result from photoneutron interactions. Specifically, the MCNPX code is applied here to the problem of dose calculations in traditional (non-IMRT) photon beam therapy. Points of calculation are located in the head, where the primary irradiation has been directed, but also in the superior portion of the torso of the ORNL Mathematical Human Phantom. We calculated dose contributions from neutrons, protons, deutrons, tritons and He-3 that are produced at the time of photoneutron interactions in the body and that would not have been accounted for by conventional radiation oncology dosimetry

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

    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)

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

    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.)

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

    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

  20. A comparison of a short half-life marker (low-dose isoniazid), a long half-life pharmacological indicator (low-dose phenobarbitone) and measurements of a controlled release 'therapeutic drug' (metoprolol, Metoros) in reflecting incomplete compliance by volunteers.

    Hardy, E.; Kumar, S; Peaker, S; Feely, M; Pullar, T

    1990-01-01

    1. Although, long half-life compounds appear to be more appropriate pharmacological indicators of compliance with treatment, short half-life markers or measurements of short half-life therapeutic drugs are frequently used. 2. We have compared the usefulness of low-dose phenobarbitone (a long half-life indicator), low dose isoniazid (a short half-life marker) and controlled release metoprolol (Metros) (a controlled release formulation of a short half-life 'therapeutic' drug) in seven volunteer...

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

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

    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...

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

    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

  4. A Therapeutic Dose of Ketoprofen Causes Acute Gastrointestinal Bleeding, Erosions, and Ulcers in Rats

    Shientag, Lisa J; Wheeler, Suzanne M; Garlick, David S.; Maranda, Louise S

    2012-01-01

    Perioperative treatment of several rats in our facility with ketoprofen (5 mg/kg SC) resulted in blood loss, peritonitis, and death within a day to a little more than a week after surgery that was not related to the gastrointestinal tract. Published reports have established the 5-mg/kg dose as safe and effective for rats. Because ketoprofen is a nonselective nonsteroidal antiinflammatory drug that can damage the gastrointestinal tract, the putative diagnosis for these morbidities and mortalit...

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

    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.)

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

    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.

  7. Predictor factors in the effectiveness of the therapeutic dose in the Graves diseases

    The treatment of the Graves diseases includes different options, between which are the antithyroid drugs, 131I and/or the surgery. Of all of them, the 131I, it has been increasing the use through the years, going to constitute the treatment of election for many authors, due to the big effectiveness to obtain a rapid healing of this illness. On the other hand, controversies exist about this use, related about the administration doses of 131I

  8. The Effect of Changing Technique, Dose, and PTV Margin on Therapeutic Ratio During Prostate Radiotherapy

    Purpose: To quantify the dosimetric and radiobiological changes seen when using intensity-modulated radiation therapy (IMRT) or planning target volume (PTV) margin reduction with consistent planning parameters in a representative sample of localized prostate cancer patients. Methods and Materials: Twenty patients were randomly selected from a cohort that received 79.8 Gy using six-field conformal radiotherapy. Using the clinical contours, PTV margin, planning system, and dose constraints, five-field IMRT plans were generated for 79.8, 83.8, and 88.0 Gy. The 88.0-Gy IMRT plan was then reoptimized with a PTV margin reduced to 3 mm. These plans were then compared using various dosimetric and radiobiological endpoints calculated for various α/β. Results: Intensity-modulated RT resulted in greater conformity to the PTV (p mod) was largely unchanged between six-field conformal and IMRT for the majority of the patients. When IMRT was used to escalate dose, NTCPrw increased by 9% at each 5% prescription increase (p mod(p = 0.005). Changes in TRmod between conformal and IMRT planning or PTV reduction showed large interpatient variability. Conclusions: Changing from conformal to IMRT, or from PTV10-7 to PTV3, did not produce a uniform interpatient increase in TRmodwhen the CTV contained the prostate alone. Radiobiological benefits of these two methods seem to be dependent on the particular anatomy of individual patients, supporting the use of patient-specific margin, planning, and dose prescription strategies

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

    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

  10. Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

    Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

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

    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...

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

    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.

  13. MCNP dose calculations in a CT phantom for therapeutic external photon beam

    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. (authors)

  14. Lateral spread of dose distribution by therapeutic proton beams in liquid water

    Abril, Isabel, E-mail: ias@ua.es [Departament de Física Aplicada, Universitat d’Alacant, E-03080 Alacant (Spain); Vera, Pablo de [Departament de Física Aplicada, Universitat d’Alacant, E-03080 Alacant (Spain); Garcia-Molina, Rafael [Departamento de Física – Centro de Investigación en Óptica y Nanofísica, Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, E-30100 Murcia (Spain); Kyriakou, Ioanna; Emfietzoglou, Dimitris [Medical Physics Laboratory, University of Ioannina Medical School, GR-45110 Ioannina (Greece)

    2015-06-01

    We have calculated the lateral spread of the dose distribution of protons in liquid water by means of the SEICS (Simulation of Energetic Ions and Clusters through Solids) code, which properly accounts for the electronic stopping force (including energy-loss straggling), multiple elastic scattering with the target nuclei, dynamical electron charge-exchange processes and nuclear fragmentation reactions between the projectile and the nuclei of the target. Due to the multiple elastic scattering processes part of the proton energy may be deposited at a given lateral distance from the initial beam direction, which is quantified by the root mean square radius (r{sub rms}). We find in our simulations that the r{sub rms} follows a parabolic dependence as a function of the depth in the target and the quotient between the r{sub rms} at the Bragg peak and the depth of the Bragg peak is around 3% independently of the proton energy. A rather good agreement is obtained when comparing our results of r{sub rms} with experimental data and with other models.

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

    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

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

    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. ...

  17. 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

    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)

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

    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

  19. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Araujo, Francisco de; Santas, Bernardo Maranhao; Dantas, Ana Leticia Almeida; Lucena, Eder Augusto [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: faraujo@ird.gov.br; Melo, Rossana Corbo de; Rebelo, Ana Maria de Oliveira [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2007-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology to evaluate therapeutic doses through the determination of biokinetic parameters and the activity of {sup 131}I deposited in the thyroid of patients submitted to the treatment of hyperthyroidism with {sup 131}I. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The calculation of the calibration factor of the scintillation camera allows the determination of activities in the thyroid of patients in pre-established time periods through a 48-hours uptake curve. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were 39.3 {+-} 0.8 and 4.3 {+-} 0.2 respectively. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use

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

    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.

  1. 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

    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

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

    .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)

  3. Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

    Aloísio Sales da Cunha

    1987-10-01

    Full Text Available A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ and the quantitative Kato-Katz (K-K methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28% and K-K (80% became significative. When this number dropped to less than 2,000 the percentage of false negative

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

    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

  5. Dose-rate and the reciprocity law: the TL response of Ge-doped silica optical fibres at therapeutic radiation doses

    In the radiotherapy regime, the TL response of Ge-doped optical fibre is investigated with respect to photon and electron dose-rate. The flexible optical fibre dosimeter system has previously been shown by this group to provide sensitive dosimetry over a wide range of electron and photon dose, sufficient to provide for the needs of radiotherapy. The optical fibre also offers small physical size and hence high spatial resolution. While TL measurements reveal linear dose response over the useful range of absorbed dose from 1 - 5 Gy, we know of no previous measurements of response to dose rate. Herein, for the dose range 1 - 5 Gy, we explore dose rates of 100 - 1000 cGy min-1 using a 9 MeV electron beam and 100 - 600 cGy min-1 using a 6 MV photon beam. For fixed doses we examine flatness of response over the cited dose-rate ranges. For electron and photon beams respectively, the optical fibre detectors were found to give flat response to within 4% and 5%, being independent of dose rate to within 2% (1 S.D.) for both electron and photon beam therapy. (Authors)

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

    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

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

    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.

  8. Dose-rate and the reciprocity law: TL response of Ge-doped SiO2 optical fibers at therapeutic radiation doses

    An investigation has been made on commercially available Ge-doped SiO2 optical fibers as a novel thermoluminescence system for radiotherapy dosimetry. This dosimeter has previously been shown by the group to provide sensitive dosimetry over a wide range of electron and photon dose, suitable for the needs of radiotherapy. In addition the optical fiber offers small physical size (125 μm diameter) and hence high spatial resolution. The reciprocity between thermoluminescence (TL) yield of Ge-doped SiO2 optical fibers and dose has been investigated for fixed radiation dose for a range of photon and electron dose rates. For electron beams of nominal energies in the range of 9-20 MeV, we have investigated the TL response of these fibers for dose rates between 100 and 1000 cGy min-1. For photon beams of nominal energies in the range of 6-15 MV, we have used dose rates of 100-600 cGy min-1. Reproducibility and fading at fixed absorbed dose (3 Gy) and dose rate for the optical fibers were also investigated. At fixed dose rates, the TL optical fibers were found to produce a flat TL yield within 4% (1σ) and 3% (1σ) for electron and photon beams, respectively. The optical fibers demonstrated good reproducibility (±1.5%), low residual signal for a readout temperature of 300 oC and negligible fading. A weak dependence on dose-rate has been observed in the range of 3.4-3.9% for electrons (with an associated uncertainty of 4%) and 2.4-2.9% for photons (with an associated uncertainty of <4%). For electron and photon energies we note a consistent trend towards lower response in the TL yield of between 3.4-3.9% and 2.4-2.7%, respectively, at the higher dose rates in comparison with the response at lower dose rates. In addition we note an appreciable systematic energy dependence for both electron and photon beams. It is important to take such factors into account for providing precise and accurate radiotherapy dosimetry. It is also apparent that the optical fibers can be re

  9. Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent

    Samaneh Zolghadri

    2015-06-01

    Full Text Available Due to interesting therapeutic properties of 177Lu and tumor avidity of tetraphenyl porphyrins (TPPs, 177Lu-tetraphenyl porphyrin was developed as a possible therapeutic compound. 177Lu of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3sample with thermal neutron flux of 4 × 1013 n.cm-2.s-1. Tetraphenyl porphyrin was synthetized and labeled with 177Lu. Radiochemical purity of the complex was studied using Instant thin layer chromatography (ITLC method. Stability of the complex was checked in final formulation and human serum for 48 h. The biodistribution of the labeled compound in vital organs of wild-type rats was studied up to 7 d. The absorbed dose of each human organ was calculated by medical internal radiation dose (MIRD method. A detailed comparative pharmacokinetic study was performed for 177Lu cation and [177Lu]-TPP. The complex was prepared with a radiochemical purity: >97±1% and specific activity: 970-1000 MBq/mmol. Biodistribution data and dosimetric results showed that all tissues receive approximately an insignificant absorbed dose due to rapid excretion of the complex through the urinary tract. [177Lu]-TPP can be an interesting tumor targeting agent due to low liver uptake and very low absorbed dose of approximately 0.036 to the total body of human.

  10. 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.

    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

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

    Jagetic, Lydia J.; Newhauser, Wayne D.

    2015-06-01

    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. 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.

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

    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

  13. Chromosomal aberrations detected by chromosome painting in lymphocytes from cancer patients given high doses of therapeutic X-rays

    Chromosome painting by fluorescence in situ hybridization (FISH) with a whole chromosome-specific DNA probe was used to detect chromosomal aberrations in lymphocytes from cancer patients given partial-body fractionated X-ray therapy. Six male patients with cancer of the stomach, prostate, lung, or hepatocellular carcinoma, received X-rays in total doses of 40.5 to 70.08 Gy. Lymphocytes were cultured for 50 h with phytohemagglutinin. The mean frequency of aberrant cells detected by chromosome 4 painting varied from 1.57% to 14.34% in the patients and was markedly higher than in healthy controls (mean=0.12%). Chromosome painting effectively detected chromosomal aberrations in lymphocytes from cancer patients. Equivalent biological doses extrapolated from a dose-response curve obtained in an in vitro human lymphocyte X-ray irradiation study are discussed as an indicator of the cytogenetic damage inducible by radiotherapy in cancer patients. (author)

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

    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)

  15. Verification of the absorbed dose values determined with plane parallel ionization chambers in therapeutic electron beams using ferrous sulfate dosimetry

    Absolute and relative dosimetry measurements in clinical electron beams using different detectors were performed at a Philips SL18 accelerator. For absolute dosimetry, ionization chamber measurements with the PTW Markus and PTW Roos plane parallel chambers were performed in water following the recommendations of the TRS-381 Code of Practice, using different options for chamber calibration. The dose results obtained with these ionization chambers using the electron beam calibration method were compared with the dose response of the ferrous sulphate (Fricke) chemical dosimeter. The influence of the choice of detector type on the determination of physical quantities necessary for absolute dose determination was investigated and discussed. Results for dmax, R50 and Rp were in agreement within statistical uncertainties when using a diode, diamond or plane parallel chamber. The effective point of measurement for the Markus chamber is found to be shifted 0.5 mm from the front surface of the cavity. Fluence correction factors, hm, for dose determination in electron beams using a PMMA phantom were determined experimentally for both plane parallel chamber types. (author)

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

    Andersen, O; Nielsen, M K; Eriksen, P B; Fenger, M; Knudsen, P J

    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...... theophylline concentration....

  17. Electrospray LC-MS and the use of controlled isotope (12C : 14C) dosing for the structural elucidation of soil metabolites of a cereal herbicide

    DE-570 is a herbicide developed by Dow AgroSciences LLC for the control of broad leaf weeds in cereal crops. Laboratory metabolism studies to determine the route and rate of degradation of 14C labelled DE-570 in soil indicated the formation of a number of metabolites which required identification to satisfy European and North American regulatory guidelines. This paper describes the work carried out by Electrospray (ESI) LC-MS for the structural elucidation of these metabolites and discusses a novel approach of using controlled isotopic (12C/14C) dosing of the parent herbicide to aid the metabolite identification process

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

    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....

  19. Plasma and brain concentrations of oral therapeutic doses of methylphenidate and their impact on brain monoamine content in mice

    Balcioglu, Aygul; Ren, Jia-Qian; McCarthy, Deirdre; Spencer, Thomas J.; Biederman, Joseph; Bhide, Pradeep G

    2009-01-01

    Methylphenidate is a frequently prescribed stimulant for the treatment of attention deficit hyperactivity disorder (ADHD). An important assumption in the animal models that have been employed to study methylphenidate’s effects on the brain and behavior is that bioavailability of methylphenidate in the animal models reflects that in human subjects. From this perspective, the dose and route of administration of methylphenidate assume critical importance because both these factors likely influen...

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

    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

  1. Preparation of 14C-labelled urea for diagnosis of helicobacter pylori infection

    The preparation of 14C-urea from [14C]-barium carbonate is reported. The results show that chemical yield can reach 80% (average of 6 runs); melt point is 132 - 136 degree C; purity is 99.65% - 99.85%. After being analyzed by IR, UV, NMR, MS, and elemental analysis, the 14C-urea has the same molecular structure as that of standard urea. Animal trial indicates that clinical use is safe. Good stability is shown by stability testing under different luminous flux, temperature and relative humidity

  2. Simple syntheses of 3-substituted indoles and their application for high yield 14C-labelling

    Methods are described which allow the synthesis of several plant indole alkaloids and their metabolites at different scales. Compounds synthesized include gramine (1) (3-dimethylaminomethylindole) which is directly derived from indole, while its biosynthetic precursors 3-aminomethylindole (3) and 3-methylaminomethylindole (2) as well as indole3-carboxylic acid (7) are synthesized via indole-3-aldehyde (6). Slight changes of the experimental conditions allow syntheses with high yields not only at the molar but also at the μmolar level. This is extremely useful when isotope labelled compounds of high specific radioactivity are required for studies of plant metabolism. (orig.)

  3. Penetration of 14C-labelled methyl parathion in Tribolium castaneum (Herbst)

    Studies on the rate of penetration of radioactive methyl parathion (14C-ri ng labelled) were conducted under laboratory conditions, by applying 5 ng toxicant in 1μl acetone/insect on the thoracic sternum of rust red flour beetle, Tribolium castaneum (Herbst). Results revealed that the penetration of this toxicant was non-linear with two distinct phases. The earlier phase was faster and lasted upto 60 min from the time of application (half-life:14±3 min) followed by a slower phase from 60 min to 24 hr with longer half-life (909± 313 min). It was further observed that at the end of the faster phase i.e., 1 hr after treatment, nearly 68 per cent of the applied insecticide was absorbed by the beetle whereas the maximum quantity of the toxicant absorbed by the insect at the end of the experiment (24 hr after treatment) was 89 per cent. (author). 27 refs

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

    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)

  5. Investigations on the uptake of 14C-labelled chlorhexidine diglutonate through dental enamel

    In this dissertation it was shown using radioactively labelled 14C tracer molecules that chlorhexidine is adsorbed on the dental surface of extracted teeth. Evidence for this was provided by the three following methods: a) back diffusion and release in rinses; b) thin layer chromatography of the adsorbed substance, and c) autoradiography. (orig./MG)

  6. Metabolic fate of the (14)C-labeled herbicide clodinafop-propargyl in soil.

    Jaquet, Jasmin; Weitzel, Pascal; Junge, Thorsten; Schmidt, Burkhard

    2014-01-01

    The metabolic fate of (14)C-phenyl-labeled herbicide clodinafop-propargyl (CfP) was studied for 28 days in lab assays using a soil from Germany (Ap horizon, silt loam, and cambisol). Mineralization amounted to 12.40% of applied (14)C after 28 days showing a distinct lag phase until day 7 of incubation. Portions of radioactivity extractable by means of 0.01 M CaCl2 solution (bioavailable fraction) decreased rapidly and were 4.41% after 28 days. Even immediately after application, only 57.31% were extracted with the aqueous solvent. Subsequent extraction using accelerated solvent extraction (ASE; acetonitrile/water 4:1, v/v) released 39.91% of applied (14)C with day 0 and 26.16% with day 28 of incubation from the samples. Non-extractable portions of radioactivity thus, increased with time amounting to 11.99% (day 0) and 65.00% (day 28). A remarkable increase was observed between 14 and 28 days correlating with the distinct increase of mineralization. No correlation was found throughout incubation with general microbial activity as determined by DMSO reduction. Analysis of the CaCl2 and ASE extracts by radio-TLC, radio-HPLC and GC/MS revealed that CfP was rapidly cleaved to free acid clodinafop (Cf), which was further (bio-) transformed; DT50 values (based on radio-TLC detection of the parent compound) were far below 1 day (CfP) and about 7 days (Cf). TLC analysis pointed to 2-(4-hydroxyphenoxy)-propionic acid as further metabolite. Due to fractionation of non-extractable residues, most of the (14)C was associated with fulvic and humic acids, portions in humin fractions and non-humics were moderate and low, respectively. Using a special strategy, which included pre-incubation of the soil with CfP and then mineralization of (14)C-CfP as criterion, a microorganism was isolated from the soil examined. The microorganism grew using CfP as sole carbon source with concomitant evolution of (14)CO2. The bacterium was characterized by growth on commonly used carbon sources and by 16S rDNA sequence analysis. The sequence exhibited high similarity with that of Rhodococcus wratislaviensis (99.56%; DSM 44107, NCIMB 13082). PMID:24502211

  7. A method for monitoring mineralization of 14C-labeled compounds in aqueous samples

    Previously reported laboratory methods for measuring the rate of 14CO2 release from an aqueous sample require a series of replicate growth flasks. At chosen times, some of these are sacrificed in order to quantitate the 14CO2 released. The method presented here requires only one culture flask containing 200 ml of sample with labeled substrate, and one control-replacement flask containing 200 ml of sterile sample with labeled substrate. At each sampling time, 1/40th of the liquid and headspace gas is removed from the modified 500 ml Erlenmeyer culture flask for 14CO2 recovery. This method was used to study the mineralization of labeled amino acids, starch, n-hexadecane and anthracene by micro-organisms in river water, and of n-hexadecane and n-hexadecanoic acid by microorganisms in sewage effluent. (author)

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

    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. Studies on the distribution of 14C-labelled PCB in the body, 4

    This paper is a report of 14C-PCB distribution series in animals. We reported the results of the distribution of 14C-PCB from birds, fish and shell in the previous experiments, and we have obtained some results from present experiment. This time interperito neal injection of 14C-PCB solution was carried to mice, and the results were as follows; Excretion of 14C-PCB as radioactivity was at its maximum about 6 hr. after medication. Excretive ratio was 87.20% for 24 hr, but 72.43% of radioactivity was excreted within 12hr. The result of radiopaperchromatography showed that 14C-PCB was not changeable in the fecus after medication, being Rf = 0.92 in comparison with standard 14C-PCB. 14C-PCB distributed throughout the body of mice in 24 hr. and at least remained over till 480 hr. in adipose tissues of mice after single medication. (auth.)

  10. Transport of 14C-labeled indoleacetic acid in Vicia root segments

    IAA transport in Vicia root segments was investigated for comparison with that in intact roots. Lanolin paste (1-mm-wide ring) or agar blocks (3 x 3 x 1.5 mm), both containing IAA-2-14C, were applied to the surface or a cut end of the root segments, respectively; transported 14C was collected in receiver agar blocks placed on the cut end of the segments. When lanolin paste was applied to 5-mm segments, basipetal transport of IAA redominated over acropetal transport. When agar blocks were applied to 1- and 2-mm segments, the same was true; in longer segments (3 and 5 mm long), however, basipetal movement occurred predominantly at first but was surpassed by acropetal movement after 2 - 3 hr. Among the segments tested (regions 2 - 4, 4 - 6 and 8 - 10 mm from the tip), the most apical one showed the distinctest predominancy of basipetal movement. The velocities of the acropetal and basipetal movement of the 14C were estimated at 3 - 3.8 and 8 - 12 mm/hr, respectively. Autoradiographic study and the experiment in which wire was inserted longitudinally through the central part of the segments showed that basipetal movement occurred mainly through the outer part of the roots and acropetal movement mainly through the central cylinder. The present results were compatible with those obtained previously with intact roots. Some properties of polar movement, such as its specificity, inhibition by TIBA, and dependency on temperature are described. (author)

  11. Some metabolic pathways in the blue - green alga micro cystis aeruginosa using 14 C - Labelled compounds

    Blue - green algae (cyanobacteria) are of world Wied distribution in fresh water, their toxic and nontoxic strains are forming heavy blooms regularly in eutrophic natural water. They grow rapidly under many physicochemical stresses even in many domestic sewage (Skulberg et al., 1984). The toxic and nontoxic strains are morphologically indistin - guishable, so extensive toxicity testing must be taken into consideration and is so much essential because some species are marketed to human consumption as a food. From the toxicological point of view, at least five genera are now known as toxic strains, these are anabaena, nostoc, oscillator, aphanizomenon, micro cystis (Carmichael, 1981; Carmichael and Mahmood, 1984, and carmichael et al, 1985). The toxicity levels of these species are varied widely with regard to site, season, week or even day of collection (Carmichael and Gorham, 1981). Such variability may be correlated to the changes in species composition. The intensive growth of toxin producing organisms in municipal and recreational water supplies affect human health both wild and domestic animals, Livestock, pets, fish and birds in many countries and are suspected to cause the last and smell of drinking water to be unpleasant (Beasley et al, 1983 and carmichael et al, 1985)

  12. Radio photosynthesis of some 14 C-labelled sugars using the unicellular green alga scenedesmus ACUTUS

    Radiosynthesis has been carried out using the unicellular green alga scenedesmus acutus together with Na H 14 CO3 solution as a carbon-14 source, in an ordinary photosynthesis chamber. The process is more easier and less laborious than the techniques involving the use of gaseous 14 CO2 in a tight photosynthesis chamber. Uniformly labelled 14 C-glucose, 14 C-fructose and 14 C-sucrose have been prepared with specific activities of several micro curies per milli mole. The specific activity of the products was found to increase on increasing the photosynthesis time or the initial activity of the Na H 14 CO3 solution used. 3 tabs

  13. Radioimmunoassay for antigliadin-antibodies using 14C-labelled gliadin

    A sensitive radioimmunoassay for antibodies to gliadin has been developed. Gliadin from wheat gluten was labelled with [1-14C]acetic anhydride to a specific activity of 2.6 x 106 dpm/mg. Immunological evidence is presented that the antigen was not essentially altered by the labelling procedure. Experimentally-induced antigliadin antibodies or sera of patients with coeliac disease (CD) were reacted with labelled gliadin and the immune complexes formed precipitated by antiglobulin. Precipitating antibodies were determined by incubating CD sera with labelled gliadin and measuring the radioacticity in precipitates formed without the addition of second antibody. Comparison with other methods for the detection of antigliadin antibodies, including immunoelectrophoresis, immunodiffusion and passive hemagglutination indicated that total and precipitating antibodies were determined only by RIA. The assay also provides information on the immunoglobulin class of antigliadin-antibodies present in sera of patients with coeliac disease

  14. Improved Double-Vial Radiorespirometric Technique for Mineralization of 14C-Labeled Substrates †

    Coveney, Michael F.; Wetzel, Robert G.

    1984-01-01

    New procedures which simplify sample preparation and improve counting efficiency were developed for double-vial radiorespirometry. Under certain conditions, efficiency of fluor-NaOH-impregnated wicks was not stable, but was adversely affected by water vapor, NaOH concentration, and CO2 loading. Glass fiber wick material treated with a methanolic fluor-NaOH solution showed improved 14C counting efficiency (58%) compared with previous methods.

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

    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

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

    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.)

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

    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.)

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

    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.)

  19. Synthesis of 14C-labeled levamisole and 13C-labeled tetramisole

    The syntheses of 14C-ring labeled levamisole ([-]-2,3,5,6-tetrahydro-6-phenyl [14C]-UL]imidazo[2,1-b]thiazole) from acetophenone-ring-UL-14C in 5 steps plus resolution with a 7.5% overall yield, and 13C6-ring labeled tetramisole ([±]-2,3,5,6-tetrahydro-6-phenyl [13C6]imidazo[2,1-b]thiazole) from benzene-13C6 in 6 steps with a 9.0% overall yield are described. (author)

  20. Measurement of phagocytic activity in porcine blood by means of 14C-labelled glucose

    The methodological and biological variability of the 14C tracer technique was part of the problem, and the results revealed a high accuracy (s/sub %/ = 10%). Comparative studies concerning the modified opsonocytophague test were performed. The effects of pre-incubation periods, age of germ suspension, quantitative changes in the chemical samples, and aspects relating to data recording were also studied. The conclusions drawn from the results are presented in form of an instruction. (author)

  1. 3H- and 14C-labelling of the aromatase inhibitor ZK 138723

    It has been known for several years that the growth of certain neoplastic disorders - especially breast cancer in women -depends on the serum level of estrogen. One strategy of lowering the estrogen formation is to inhibit the action of the enzyme aromatase, which catalyzes the final step in estrogen biosynthesis in humans. For this purpose nonsteroidal compounds seem to offer advantages as compared to the classical steroid derivatives regarding intensity and duration of effect as well as selectivity to other cytochrome P450 enzymes. The competitive aromatase inhibitor ZK138723 is such a nonsteroidal compound. It was labelled with 3H and 14C to be used for further pharmacological investigations. (author)

  2. Determination of the migration of a plasticizer by 14C-labelled compounds

    The migration rate of a plasticizer (dioctyl phthlate 14C) from a P.V.C. film, with different media in contact with it, was determined by measurements of radioactivity in the extraction liquids. Mineral oil, vegetal, oil aliphatic hidrocarbon and detergent solution were used for this purpose. The resulting figures were compared to those obtained from weight loss determinations and in some cases the percentage of ''swelling'' of the plastic could be established. (author)

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

    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)

  4. Dynamics of penetration of 14C-labelled parathion in desert locust, Schistocerca gregaria Forskal

    Studies on the rate of disappearance of 14C ring labelled parathion, after topical application on the mesosternum of desert locust, Schistocerca gregaria Forskal, indicated that penetration of the toxicant was linear and followed first order kinetics. The first order constant (k) for parathion on desert locust was 18.42x10-2 per hr and half-life (Tsub(0.5)) was about 226 min. (author). 26 refs ., 1 fig

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

    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

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

    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

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

    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

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

    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

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

    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...

  10. Development of a methodology to determine optimized therapeutic doses of 131I for the treatment of hyperthyroidism

    Several methods can be used to determine the activity of 131I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with 131I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of 131I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and Instituto de Medicina Nuclear - IMEN, of Goiania. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were (39.3 ± 0.78), (58.1 ± 2.38) to uptake probe SCT-13004 e 13002, respectively and 4.3 ± 0.17 to scintillation camera. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use of diagnose equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable procedure in terms of effectiveness, simplicity and cost. (author)

  11. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Araujo, F.; Moura, M.B.; Pereira, A.C., E-mail: faraujo@ird.gov.br [Instituto de Medicna Nuclear (IMEN), Goiania, GO (Brazil); Dantas, B.M.; Dantas, A.L.A.; Lucena, E.A. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Melo, R.C.; Rebelo, A.M.O. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2008-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with {sup 131}I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and Instituto de Medicina Nuclear - IMEN, of Goiania. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were (39.3 ± 0.78), (58.1 ± 2.38) to uptake probe SCT-13004 e 13002, respectively and 4.3 ± 0.17 to scintillation camera. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use of diagnose equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable procedure in terms of effectiveness, simplicity and cost

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

    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

  13. 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

    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.

  14. 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

    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

  15. Therapeutic Nanodevices

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

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

    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

  17. Negative correlation between therapeutic success in radioiodine therapy and TcTUs: are TcTUs-adapted dose concepts the only possible answer?

    Gotthardt, Martin; Nowack, Miriam; Behe, Martin P.; Schipper, Meike L.; Schlieck, Anja; Hoeffken, Helmut; Behr, Thomas M. [Department of Nuclear Medicine, Philipps-University of Marburg, 35043, Marburg (Germany)

    2003-08-01

    Calculation of iodine-131 activities for radioiodine treatment (RIT) in patients with disseminated thyroid autonomy may be difficult because of uncertainties in the determination of the autonomous volume (vol{sub aut}). The algorithm established by Emrich is used for calculation of the vol{sub aut} based on the TcTUs (technetium thyroid uptake under TSH suppression) (vol{sub aut}= 5 x TcTUs+0.6). Clinical experience using this approach has shown that there is a negative correlation between increasing TcTUs and the results of RIT. Our aim was to identify the reasons for this observation as well as to assess the relation between TcTUs and sonographic vol{sub aut}. Furthermore, we intended to find an alternative algorithm for the TcTUs-based calculation of the vol{sub aut}. Data from 100 patients with unifocal autonomy who met strict inclusion criteria were used to evaluate the correlation between TcTUs and sonographic vol{sub aut}. Using Marinelli's algorithm, we calculated the therapeutic activities for a standardised patient at a target dose of 300 Gy. The vol{sub aut} was determined based on the TcTUs using the four published algorithms [Emrich 1993 (vol{sub aut}= 5 x TcTUs+0.6), Kreisig 1992 (vol{sub aut}=10 x TcTUs-9.3), Joseph 1977 (vol{sub aut}=8.33 x TcTUs-6.67) and 1994 (vol{sub aut}=2.88 x TcTUs+0.09)]. We then compared the results of the calculation of therapeutic activities obtained using Emrich's algorithm (with known success rates) with those obtained by the other algorithms in order to determine which algorithm would lead to better results in RIT. Only a weak correlation was found between the TcTUs and the sonographic vol{sub aut} (r{sup 2}=0.39). The calculated therapeutic activities of {sup 131}I were similar for all algorithms at a TcTUs of around 2% but Joseph's (1977) and Kreisig's (1992) algorithms resulted in clearly higher activities than Emrich's algorithm at a TcTUs above 2%. The need for target doses to increase with

  18. Pre-therapeutic radiobiological experiments performed at Cyclone with d(50)-Be neutrons. Comparison of RBE/absorbed dose relationships obtained for several biological criteria

    The RBE/absorbed dose relationships for d(50)-Be neutrons were determined for several biological criteria. Irradiations were performed with the isochronous cyclotron Cyclone at Louvain-la-Neuve. Neutrons are produced by bombarding a thick beryllium target with 50MeV deuterons. This energy is to be used for the clinical applications. As first biological criterion, early intestinal tolerance was assessed in BALB/c mice from LD50 determination. Abdomen only was irradiated in order to avoid interference from the bone marrow syndrome. For single fraction irradiation, an RBE value of 1.8+-0.2 was observed (LD50 neutron absorbed dose: 525 rad). Fractionated irradiation had to be used to study smaller doses per fraction. The RBE increases progressively with decreasing dose and reaches 2.8 for a neutron absorbed dose of 80 rad (i.e. for a gamma absorbed dose of about 225 rad). A further RBE increase is unlikely since, for smaller absorbed doses, the survival curve for gamma rays nearly coincides with its initial tangent. The RBE/absorbed dose relationships observed for several mammalian cell lines in vitro, although they have a rather similar shape, show significant differences. For a neutron absorbed dose of 100 rad, the RBE is about 3 for EMT6 mouse cancer cells and 2 for HF19 human fibroblasts. For chromosome aberrations in Allium cepa onion roots, observed RBE values are much higher than for mammalian cell lethality. The RBE increases regularly from 7 to 12 with decreasing neutron dose from 40 to 10 rad. Two criteria were selected: (i) the mean number of aberrations (mainly breaks) per cell in anaphase and telophase, and (ii) the fraction of cells in anaphase and telophase having at least one aberration. For growth delay in Vicia faba, the RBE increases from 2.8 to 4.4 when the neutron absorbed dose decreases from 90 to 20 rad. (author)

  19. 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

    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

  20. 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

    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

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

    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.

  2. 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

    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

  3. Measurements of Dose-Averaged Linear Energy Transfer Distributions in Water Using CR-39 Plastic Nuclear Track Detector for Therapeutic Carbon Ion Beams

    Kohno, Ryosuke; Yasuda, Nakahiro; Takeshi, Himukai; Kase, Yuki; Ochiai, Keiko; Komori, Masataka; Matsufuji, Naruhiro; Kanai, Tatsuaki

    2005-12-01

    A CR-39 plastic nuclear track detector was used as a linear energy transfer (LET) detector for carbon ion radiotherapy. We compared dose-averaged LET distributions in water obtained using the CR-39 detector for a monoenergetic beam and spread-out Bragg peak beam by calculations using the one-dimensional heavy-ion transport code used in the current heavy-ion treatment planning. We confirmed that the CR-39 detector could measure the high LET particles that are dominant contributors to dose-averaged LET. On the other hand, the CR-39 result was overestimated in the tail region of the distal edge in depth-dose distributions, due to its detection limit for lower LET particles. However, physical dose in the region is quite small. Namely, the effect of this difference on the biological dose distribution is also small. These results demonstrate that the CR-39 detector is a useful detector for measuring the LET distribution in carbon ion radiotherapy.

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

    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...

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

    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)

  6. Simple syntheses of 3-substituted indoles and their application for high yield /sup 14/C-labelling

    Schallenberg, J.; Meyer, E.

    1983-01-01

    Methods are described which allow the synthesis of several plant indole alkaloids and their metabolites at different scales. Compounds synthesized include gramine (1) (3-dimethylaminomethylindole) which is directly derived from indole, while its biosynthetic precursors 3-aminomethylindole (3) and 3-methylaminomethylindole (2) as well as indole-3-carboxylic acid (7) are synthesized via indole-3-aldehyde (6). Slight changes of the experimental conditions allow syntheses with high yields not only at the molar but also at the ..mu..molar level. This is extremely useful when isotope labelled compounds of high specific radioactivity are required for studies of plant metabolism.

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

    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)

  8. Metabolic fate of the (14)C-labeled herbicide clodinafop-propargyl in a sediment-water system.

    Yuan, Ye; Weitzel, Pascal; Schäffer, Andreas; Schmidt, Burkhard

    2015-01-01

    The metabolic fate of (14)C-phenyl-labeled herbicide clodinafop-propargyl ((14)C-CfP) was studied for 28 days in lab assays using a sediment-water system derived from a German location. Mineralization was 5.21% of applied (14)C after 28 days exhibiting a distinct lag phase until day 14 of incubation. Portions of radioactivity remaining in water phases decreased at moderate rate to 18.48% after 28 days; 62.46% were still detected in water after 14 days. Soxhlet extraction of the sediment using acetonitrile released 35.56% of applied (14)C with day 28, while 33.99% remained as non-extractable residues. A remarkable increase of bound (14)C was observed between 14 and 28 days correlating with the distinct increase of mineralization. No correlation was found throughout incubation with microbial activity of the sediment as determined by dimethyl sulfoxide reduction. Dissolved oxygen and pH value of water phases remained almost constant for 28 days. Analyses of Soxhlet extracts of the sediment and ethyl acetate extracts of water phases by radio-TLC and radio-HPLC revealed that CfP was rapidly cleaved to free acid clodinafop (Cf), which was further (bio-) transformed. DT50 values (based on radio-HPLC) were below 1 day (CfP) and slightly above 28 days (Cf). Further metabolites were not detected. Fractionation of humic and non-humic components of the sediment demonstrated that CfP's non-extractable residues were predominantly associated with fulvic acids up to 14 days of incubation (3.36%), whereas after 28 days, the majority of radioactivity was found in the humin/mineral fraction (13.30% of applied (14)C). Due to high-performance size-exclusion chromatography of the fulvic acids fraction derived from assays incubated for 28 days, this portion of (14)C was firmly, possibly covalently bound to fulvic acids and did not consist of CfP or Cf. Using an isolation strategy comprising preincubation of sediment with CfP and mineralization of (14)C-CfP as criterion, a microorganism was isolated from the sediment examined. It grew on (14)C-CfP as sole carbon source with evolution of (14)CO2. The bacterium was characterized by growth on commonly used carbon sources and 16S rDNA sequence analysis. Its sequence exhibited high similarity with that of Nocardioides aromaticivorans strain H-1 (98.85%; DSM 15131, JCM 11674). PMID:26065513

  9. Synthesis of 14C labelled acrylic derivatives: diethyl [3-14C] methylidenemalonate and isobutyl [3-14C] cyanoacrylate

    Isobutyl [3-14C] cyanoacrylate and diethyl [3-14C] methylidenemalonate were synthesized by the intermediate of their protective Diels-Alder adduct with anthracene. These adducts were obtained in a one-pot procedure by Knoevenagel condensation of [14C] paraformaldehyde with isobutyl cyanoacetate and diethyl malonate respectively in the presence of a basic catalyst and anthracene. The adducts are stable crystalline compounds easily purified by recrystallization. The olefinic target compounds were obtained in high chemical and radiochemical purity (>99%) by thermolysis at 2200C in mineral oil in the presence of maleic anhydride. (author)

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

    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

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

    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)

  12. An improved method for 14C-labeling of L-DOPS, a norepinephrine precursor amino acid

    (2S,3R)-2-Amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropionic acid (L-DOPS) (1) was efficiently labeled with carbon-14 at the 3-position of the propionic acid moiety for use in mammalian metabolic studies. Condensation of 3,4-bis(benzyloxy) =carbonyl-14C=-benzaldehyde (7) with the optically active 5-oxazolidinone (8) gave the optically active alcohol (9). Catalytic hydrogenation of 9 under acidic condition afforded 1. The overall yield of 1 was 74% from 7. (author)

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

    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.)

  14. 14 C labelled compound Laboratory of Radiochemical Research and Production Department in IFIN-HH. Forty years of experience

    The first experiments with 14 C in Romania took place in the Institute of Atomic Physics (IFA) in Bucharest. The laboratory for C-14 labelled compounds, with its current structure was conceived by IFA in co-operation with GEC and AERE - England, and designed by IFA and I.P. Carpati. It was built between 1975-1977. The way it was conceived makes it the only laboratory in Romania which can offer various specialized services to interested organizations. The laboratory is able to develop the following types of activity: - primary processing of row materials with 14 C; - chemical syntheses and biosyntheses of labelled organic and inorganic compounds; - production of 14 C tracers; - specific chemical analyses involving 14 C processing. Till now among the most important results the following could be mentioned: over 60 C-14 labelled organic and inorganic compounds; over 20 publications; about 50 certified products and technologies; delivery of C-14 labelled products all over the country, in over 20 research institutes, hospitals and universities; - experiments with tracers for food industry, agriculture and livestock farms; - solutions with C-14 - calibration standards for internal use. Presently the Laboratory is conducting in cooperation with the Institute for Nuclear Research, Pitesti works for recovering of 14 C from gaseous effluents of CANDU-600 Reactor of NNP-Cernavoda. Also, works are done concerning the synthesis with 13 C and 14 C of miscellaneous organic compounds, i.e., 3N-[1-13 C] Capronylphenylthiourea, trans-derma pharmaceutic systems and N -[1 - 13 C,T] pentadecyl pyridinium bromide (both doubly labelled with T and 14 C with high specific activities at known positions); the last two compounds was certified too. The path ways for labelling and analyses are in agreement with the international techniques adopted in this field. (authors)

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

    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.)

  16. Whole-body distribution of 14C-labeled silica nanoparticles and submicron particles after intravenous injection into Mice

    We analyzed the whole-body distribution of 14C–ADP-labeled silica nanoparticles (14C–ADP–SiO2 nanoparticles) and submicron particles (14C–ADP–SiO2 submicron particles) after intravenous injection into ICR mice. The 14C–ADP–SiO2 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 14C–ADP–SiO2 nanoparticles or the 14C–ADP–SiO2 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 14C–ADP–SiO2 nanoparticles-exposed mice, whereas the retention percentage in the kidney was statistically higher in the 14C–ADP–SiO2 submicron particles-exposed mice. Both types of 14C–ADP–SiO2 particles mainly translocated to the muscle, bone, skin, and liver, but hardly translocated to the brain and olfactory bulb. Furthermore, the 14C–ADP–SiO2 nanoparticles had a higher retention percentage (62.4 %) in the entire body at 24-h post-injection than did the 14C–ADP–SiO2 submicron particles (50.7 %). Therefore, we suggested that the 14C–ADP–SiO2 nanoparticles might be more likely than the 14C–ADP–SiO2 submicron particles to be retained in the body, and consequently they might be gradually accumulated by chronic exposure.

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

    Bruun, S.; Christensen, B.T.; Thomsen, I.K.; Jensen, Erik Steen; Jensen, L.S.

    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 and...... advective movement. The model was used to interpret the distribution of C-14 in the soil profile 41 years after the labeling event. The model fitted the observed distribution of C-14 well (R-2 = 0.988, AIC(c) = -82.6), with a dispersion constant of D = 0.71 cm(2) yr(-1) and an advection constant of v = 0.......0081 cm yr(-1). However, the model consistently underestimated the amount of OM in the soil layers from 27 to 37 cm depth. A possible explanation for this is that different fractions of OM are transported by different mechanisms. For example, particulate OM, organomineral colloids and dissolved OM are not...

  18. Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate

    Purpose: To evaluate the optimal dose of methotrexate (MTX) and the efficacy of other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary brain lymphomas. Methods and Materials: Two hundred eighty-eight immunocompetent patients with histologically documented, previously untreated primary brain lymphomas, receiving CHT containing high-dose MTX (≥1 g/m2) with or without RT were selected from 19 prospective series. The impact on survival of the MTX dose (2 vs.≥3 g/m2), the main drugs, intrathecal CHT, and combination CHT (mono-CHT vs. poly-CHT) was assessed, according to the intention-to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT) was evaluated in 119 patients with a complete response to CHT. The whole brain and tumor bed dose (2 (p=0.04), thiotepa (p=0.03), and intrathecal CHT (p=0.03) improved the OS, and nitrosoureas (p 0.01) correlated with a worse survival. In multivariate analysis, limited to patients receiving MTX ≥3 g/m2, only the addition of cytarabine improved the OS; nitrosoureas reduced MTX efficacy. Of the 119 complete responders, 70 received immediate RT. A RT dose of ≥40 Gy to the whole brain or tumor bed did not improve OS. The 3-year OS was similar between the immediate and delayed RT groups. In multivariate analysis, RT delay had no negative impact on survival. Conclusions: MTX ≥3 g/m2 seems to improve survival in primary brain lymphoma patients. The efficacy of additional drugs, except for cytarabine, remains unproved. Randomized trials are needed to confirm that RT withdrawal yields no detrimental effect in complete responders

  19. 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

    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

  20. Determination of dose coefficients and urinary excretion function for inhalation of carbon-14-labelled benzene

    Based on existing pharmacokinetic models for benzene, the distribution and retention of activity after inhalation of 14C-labelled benzene in humans were studied. Six different benzene concentrations from 0.1 to 10,000 ppm (corresponding to activity concentrations between 9.6 x 106 and 9.6 x 1011 Bq m-3) and five exposure times from 0.1 to 1000 min were considered. The cumulated activities in the different organs and tissues and the urinary excretion rates were observed to depend non-linearly on the activity intake. The fraction of activity removed via urine varies between 52 and 10% of the intake. Nevertheless, for times that are long compared to the exposure duration the urinary excretion rate is determined by the activity clearance from adipose tissue and thus decreases at a constant rate. This decrease is common for all exposure conditions examined and thus allowed determining a mean urinary excretion rate and corresponding dose coefficients for committed equivalent doses as well as for the effective dose. The uncertainty of the dose coefficients is estimated to be about 50% for the exposure range covered. A 14-day interval for the incorporation monitoring by urine activity counting seems to be reasonable. (author)

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

    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. PMID:25502612

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

    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.)

  3. Late Relapses Following High-Dose Autologous Stem Cell Transplantation (HD-ASCT) for Hodgkin Lymphoma (HL) in the ABVD Therapeutic era

    Keller, Sarah F.; Kelly, Jennifer L.; Sensenig, Elizabeth; Andreozzi, Jennifer; Oliva, Jamie; Rich, Lynn; Constine, Louis; Becker, Michael; Phillips, Gordon; Liesveld, Jane; Fisher, Richard I.; Bernstein, Steven H.; Friedberg, Jonathan W.

    2011-01-01

    Salvage chemotherapy followed by high dose autologous stem cell transplantation (HD-ASCT) is the standard of care for patients who have relapsed or refractory Hodgkin Lymphoma (HL). Few trials have had long-term follow-up post HD-ASCT in the ABVD era of treatment. We reviewed 95 consecutive patients who received HD-ASCT for relapsed or refractory HL following ABVD failure between 1990 and 2006 at the University of Rochester. Median follow-up for survivors was 8.2 years. All patients received HD-ASCT following up-front ABVD (or equivalent) failure. At 5 years, overall survival (OS) and event-free survival (EFS) were 54% and 37%, respectively. In total, 54 patients have died; 37 of these patients died directly of HL. Notably, there were 19 deaths > 3 years post HD-ASCT and 13 of these late deaths are directly attributable to HL. Furthermore, there were 51 documented relapses, 9 of which occurred >3 years post HD-ASCT. In contrast to other studies, we did not observe a plateau in EFS following transplantation. Patients appear to be at continuous risk of recurrence beyond 3 years after HD-ASCT. Our results emphasize the importance of long-term follow-up for both toxicity and recurrence, and have important implications in defining success of post-transplant maintenance strategies. PMID:21871246

  4. Decreased uptake of therapeutic doses of iodine-131 after 185-MBq iodine-131 diagnostic imaging for thyroid remnants in differentiated thyroid carcinoma

    We performed a prospective random study to assess possible thyroid stunning by a 185-MBq iodine-131 dose used to diagnose thyroid remnants. Patients with differentiated thyroid carcinoma were included after total or near-total thyroidectomy. They were randomly assigned to two groups. In group 0 (G0, 32 patients), iodine-123 administration only was used to diagnose thyroid remnants and/or metastasis, so that no thyroid stunning by 131I would occur. In group 1 (G1, 19 patients), diagnostic imaging was performed with 123I and 185 MBq 131I. 123I imaging was less sensitive than 131I imaging in identifying thyroid remnants in both groups (94%). Thyroid uptake of 123I was measured in both groups (at 2 h) and was not significantly different between the groups. Patients with thyroid remnants who remained in the study (28/32 in G0, 17/19 in G1) were treated with 370 MBq 131I, 5 weeks after treatment (mean time, range 12-84 days). In 12/17 G1 patients thyroid uptake measurement was repeated immediately before treatment. Uptake was equal to 1.97%±0.71% and significantly lower (P131I decreases thyroid uptake for several weeks after administration and can impair immediate subsequent 131I therapy; (2) 123I is slightly less sensitive than 131I in identifying thyroid remnants; and (3) the need to scan for thyroid remnants remains to be confirmed, since only 2/51 patients enrolled in this study were not treated with 131I. (orig.)

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

    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.

  6. Therapeutic applications of radiopharmaceuticals

    Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

  7. Feedlot therapeutics.

    Apley, M D; Fajt, V R

    1998-07-01

    This article discusses therapeutic approaches to conditions commonly encountered in feedlots. Challenges discussed include bovine respiratory complex, tracheal edema, atypical interstitial pneumonia, footrot, toe abscesses, mycoplasma arthritis, cardiovascular disease, lactic acidosis, bloat, coccidiosis, central nervous system diseases, abscesses and cellulitis, pregnancy management and abortion, and ocular disease. PMID:9704416

  8. Correlation between γ-ray-induced DNA double-strand breakage and cell killing after biologically relevant doses: analysis by pulsed-field gel electrophoresis

    We examined the degree of correlation between γ-ray-induced lethality and DNA double-strand breaks (dsbs) after biologically relevant doses of radiation. Radiation lethality was modified by treating 14C-labelled Chinese hamster ovary cells with either of two aminothiols (WR-1065 or WR-255591) and the associated effect on dsb induction was determined by pulsed-field gel electrophoresis (PFGE). The use of phosphorimaging to analyse the distribution of 14C-activity in the gel greatly improved the low-dose resolution of the PFGE assay. Both WR-1065 and WR-255591 protected against dsb induction and lethality to a similar extent after low doses of radiation. although this correlation broke down when supralethal doses were used to induce dsbs. Thus, the level of dsbs induced in these cells as measured by PFGE after survival-curve doses of γ-radiation is consistently predictive of the degree of lethality obtained, implying a cause-effect relationship between these two parameters and confirming previous results obtained using the neutral filter elution assay for dsbs. (author)

  9. 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

    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.

  10. Therapeutic ultrasound

    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)

  11. Therapeutic alliance.

    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

  12. Therapeutic ultrasound

    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)

  13. 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

    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.

  14. 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

    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.

  15. Prenatal radiation doses from radiopharmaceuticals

    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)

  16. Diagnostic and therapeutic radiation exposure

    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.)

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

    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%...

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

    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.

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

    Ingerslev, F.; Nyholm, Niels

    2000-01-01

    ) concentrations in surface water systems. The basic principle of measurement was to determine evolved CO2 indirectly from measurements of total organic activity in subsamples after stripping off their content of CO2, Used with surface water alone the test simulates a pelagic environment and amended with sediments......A simple shake-flask surface water biodegradability die away test with C-14-labeled chemicals added to microgram per liter concentrations (usually 1-100 mu g/L) is described and evaluated. The aim was to provide information on biodegradation behavior and kinetic rates at environmental (low...... (0.1-1 dry weight/L) the test is intended to simulate a water environment with suspended solids (e.g., resuspended sediments). A protocol of the test used with the C-14 technique or with specific chemical analysis was recently developed by the International Organization for Standardization. Practical...

  20. 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.

    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

  1. Fumigation of Folia belladonnae with 14C-labelled ethylene oxide to reduce the germ number - activity distributions in the drug and preparations made from it

    The study described here provided evidence to prove that considerable quantities of ethylene oxide, ethylene chlorhydrin and ethylene glycol are retained, when a drug is fumigated with ethylene oxide under standard fumigation conditions in order to reduce the germ number. Ethylene oxide bound by adsorption may be eliminated from the drug by repeated aeration. If an aqueous-ethanolic percolate is prepared from a drug showing very high levels of ethylene chlorhydrin and then carefully distilled at 40 C using only little pressure, a dry extract can be obtained that contains no such residue. (orig.)

  2. Adrenal androgen 11β- and 19-hydroxylation: a study on kinetic isotope effect and metabolic switching of 3H and 14C labeled substrates

    Monooxygenations at 11β and 19 are two main metabolic pathways of androstenedione (A) by sheep and dog adrenals and could be catalyzed by a single cytochrome P-450 as observed for deoxycorticosterone metabolism with the bovine adrenal cytochrome P-450/sub 11β/. They found an unusually high apparent kinetic isotope effect (k/sub H//k/sub T/ = 11.7) on the 19-hydroxylation of [19-3H3, 4-14C]A with sheep and dog adrenal homogenates. They therefore attempted to assess the inverse secondary kinetic isotope effect of the simultaneously occurring 11β-hydroxylation. The substrate (16.1μM and 14.7μM, 3H/14C = 15.1 and 21.9 for sheep and dog, respectively) was incubated with adrenal tissue homogenate in the presence of NADPH for 1-10 min. The products were mixed with carrier standards and purified through TLC, acetylation, and countercurrent distribution to show constant 3H/14C ratio. The 3H/14C ratios of the major [19-3H3, 4-14C]-11β-OHA were found to be elevated 1.1-1.2 fold whereas those of [19-3H2, 4-14C]-19-OHA were decreased to 0.06 and the recovered A showed 0.95-0.99 of the initial ratio. While they observed a metabolic switching between the 2β- and 19-hydroxylations of [19-3H3, 4-14C]A with human placental aromatase (Fronckowiak and Osawa), it is suggested that adrenal non-aromatizing androgen 19-hydroxylation operates a metabolic switching with the 11β-hydroxylation

  3. 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

    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)

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

    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

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

    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 Hi Safe 3, Ultima-GoldTM AB (biodegradable) and Insta-Gel-XF (non-biodegradable), in terms of [14 C]-glucose and [3 H]-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 14 C and 3 H 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 3 H and 14 C 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. (author)

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

    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)

  7. Bioconcentration and depuration of (14) C-labeled 17α-ethinyl estradiol and 4-nonylphenol in individual organs of the marine bivalve Mytilus edulis L. .

    Ricciardi, Karen L; Poynton, Helen C; Duphily, Brian J; Blalock, Bonnie J; Robinson, William E

    2016-04-01

    Endocrine-disrupting compounds (EDCs), including 17α-ethinyl estradiol (EE2) and 4-nonylphenol (4-NP), enter coastal environments primarily in effluents of wastewater treatment facilities and have become ubiquitous in marine surface waters, sediments, and biota. Although EE2 and 4-NP have been detected in marine shellfish, the kinetics of bioconcentration and their tissue distribution have not been thoroughly investigated. The authors performed bioconcentration and depuration experiments in the blue mussel, Mytilus edulis, with 3.37 nM EE2 (0.999 μg/L) and 454 nM 4-NP (100.138 µg/L). Mussels and seawater were sampled throughout a 38-d exposure and a 35-d depuration period, and 6 tissues were individually assayed. Uptake of EE2 and 4-NP was curvilinear throughout exposure and followed a similar uptake pattern: digestive gland > gill ≥ remaining viscera > gonad > adductor > plasma. Depuration varied, however, with half-lives ranging from 2.7 d (plasma) to 92 d (gill) for EE2 and 15 d (plasma) to 57 d (gill) for 4-NP. An innovative modeling approach, with 3 coupled mathematical models, was developed to differentiate the unique roles of the gill and plasma in distributing the EDCs to internal tissues. Plasma appears pivotal in regulating EDC uptake and depuration within the whole mussel. Environ Toxicol Chem 2016;35:863-873. © 2015 SETAC. PMID:26126666

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

    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.

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

    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...

  10. Effect of feeding levels on the milk yield and on the incorporation of 14C labelled Volatile Fatty Acids in rumen into the milk

    It has been known that milk production was influenced by the feeding schedule, such as hay vs silage and ratio or concentrate to roughage, which have an important effect upon the VFA (volatile fatty acid) production in the rumen. This experiment were conducted using acetate-1-14C, propionate-1-14C, and butylate-1-14C, to examine the effect of nutritional feeding levels on the milk yield and on the incorporation rate of ruminal VFA-1-14C into the milk components. The experiment using six Holstein cows, had two periods, with different levels of concentrate feeding. In the first period, the concentrate fed was a half of 4%-FCM and in the second period, its level was a half of the first one. As a roughage, corn silage and grass hay were fed. Following the reduced feeding level of the concentrate, nutrient intake, milk yield, milk component yield and the lactose percentage were all lowered, but the fat percentage was slightly increased and the casein percentage was constant while the incorporation rates of each ruminal VFA-1-14C into the milk components were also lowered, remarkably for the lactose. (auth.)

  11. Incorporation of 4-14C labeled cholesterol into the cholesterol ester fractions of plasma lipoproteins in patients with cirrhosis of the liver

    In vivo incorporation studies with 4-14C-cholesterol were performed in five patients cirrhosis of the liver. All patients showed low concentrations of total cholesterol, esterified cholesterol, and a low activity of the lecithin:cholesterol acyltransferase activity (LCAT). The pattern of incorporation corresponded to the results known from hypercholesterolemic, normocholesterolemic and hypertriglyceridemic patients. Low cholesterol ester concentrations and low LCAT activity do not modify the pattern of incorporation into the lipoprotein ester fractions. (orig.)

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

    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

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

    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.

  14. Convenient method for 14C-labelling of a series of (E)-Styrylamidines as NR2B-selective NMDA receptor antagonist

    A series of (E)-Styrylamidines labeled with carbon-14 in the 1-position, were prepared from (E)-3-aryl-acrylonitrile-[cyano-14C] as a key synthetic intermediate which has been synthesized from E-β-aryl-vinyl iodides and zinc [14C]-cyanide in the presence of tetrakis(triphenylphosphine)palladium. (author)

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

    Ingerslev, F.; Nyholm, Niels

    2000-01-01

    A simple shake-flask surface water biodegradability die away test with C-14-labeled chemicals added to microgram per liter concentrations (usually 1-100 mu g/L) is described and evaluated. The aim was to provide information on biodegradation behavior and kinetic rates at environmental (low......) concentrations in surface water systems. The basic principle of measurement was to determine evolved CO2 indirectly from measurements of total organic activity in subsamples after stripping off their content of CO2, Used with surface water alone the test simulates a pelagic environment and amended with sediments...... regular reinoculation with freshly collected surface water could, however, overcome the problems of false-negative results. (C) 2000 Academic Press....

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

    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)

  17. Therapeutical uses of 131I

    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

  18. [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].

    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

  19. Therapeutic performances of some selected aqua drugs

    Rasheduzzaman Khan Dipu; Md. Bazlur Rashid Chowdhury; Mohammad Abdullah Al Imran; Md. Abdul Quaiyum; Md. Tareq-Uz-Zaman

    2014-01-01

    This study was carried out at the Disease Laboratory of the Faculty of Fisheries, Bangladesh Agricultural University, Mymensingh, Bangladesh to verify the therapeutic performances of six commercial aqua drugs; three doses were selected as less than recommended, recommended and more than recommended to assess their performances. Before starting therapeutic experimental nine climbing perch (Anabas testudineus) and six stinging catfish (Heteropneustes fossilis) were confirmed as diseased ones by...

  20. Synergistic drug combinations improve therapeutic selectivity

    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 ...

  1. The Pharmacokinetics of Once-Daily Dosing With Gentamicin in Women With Postpartum Endometritis

    Sunyecz, J A; Wiesenfeld, H. C.; Heine, R. P.

    1998-01-01

    Conclusions: Once-daily dosing with gentamicin in women with postpartum endometritis achieves therapeutic peak levels without drug accumulation. Substantial cost savings are realized with this dosing regimen.

  2. Radiopharmaceuticals: therapeutic applications

    Radiopharmaceuticals are chemical compounds incorporating appropriate radionuclides, which are rendered suitable for human administration. It is the artificial production of radionuclide that laid the foundation of nuclear medicine. The basic principle in designing radiolabeled compounds for therapy is to achieve a high concentration of radioactivity in the target tissue which would be capable of delivering a desirable radiation dose with minimal exposure to the critical organ (usually bone marrow). With the availability of artificially produced radionuclides, therapeutic applications were initiated. Iodine-131 for the treatment of thyroid disorders has remained the most important one. Recent advances over the past 10 years are quite dramatic. There are three important areas where considerable research work is in progress. Intraarticular administration radiocolloids appear to be valuable for the management of synovitis in patients with rheumatoid arthritis. Palliative treatment of bone metastases and total-body bone marrow irradiation seem to be feasible with bone-seeking radiopharmaceuticals. Design and development of radiolabeled compounds for targeted delivery is important, such as (a) monoclonal antibodies for specific antigens, (b) peptides for specific receptors and (c) conjugated drugs for specific tumours. Radionuclide therapy is still in its infancy and present research activities reflect future potentials. (author). 76 refs., 4 figs., 2 tabs

  3. American Therapeutic Recreation Association

    ... Remember Me I forgot my password American Therapeutic Recreation Association Promoting Health & Wellness Services Annual Conference 2016 ... and leave your opinion Join thousands of Therapeutic Recreation specialists today Join Now Renew your membership today ...

  4. 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

    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.

  5. Dose determination with plane-parallel ionization chambers in therapeutic electron and photon beams. Report of the 2nd research co-ordinated meeting (326-E2-RC-641.2), March 30 - April 3, 1998, Barcelona, Spain

    In 1987, the IAEA published a report entitled 'Absorbed Dose Determination in Photon and Electron Beams: An International Code of Practice' (IAEA Technical Reports Series No. 277) to advise users how to obtain the absorbed dose in water from the measurements made with an ionization chamber, calibrated in terms of air kerma. For high-energy photons (energies above 1 MeV) the chamber calibration was at a single photon quality (Cobalt-60 gamma rays). The scientific scope of the Co-ordinated Research Project is to investigate the accuracy of the new data and procedures included in the Code of Practice IAEA TRS-381. Differences with existing recommendations, published by national organizations, are to be evaluated to analyze the possible impact on patient dosimetry. The second Research Co-ordination Meeting (RCM) was organized to revise the activities in the Co-ordinated Research Project (CRP) and the status of the various projects. The status of the on-going work under the frame of the CRP was presented by the participants in the RCM during the first two days and each contribution discussed in detail. During the following days, plans were made on the work left for each participant to complete the project and the feasibility of preparing a report describing in detail the work done in the project

  6. [Therapeutic drug monitoring of felbamate].

    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

  7. [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].

    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

  8. 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

    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)

  9. 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

    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.

  10. 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

    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.

  11. Dose limits

    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

  12. Therapeutic Recreation Practicum Manual.

    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…

  13. Chicanoizing the Therapeutic Community

    Aron, William S.; And Others

    1974-01-01

    Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

  14. Cytokines and therapeutic oligonucleotides.

    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

  15. Controllable dose

    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)

  16. Therapeutic postprostatectomy irradiation.

    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

  17. 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

    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.

  18. Antiviral Polymer Therapeutics

    Smith, Anton Allen Abbotsford

    2014-01-01

    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...... the examples of polymer therapeutics being applied as an antiviral treatment are few and far in-between. This work aims to explore antiviral therapeutics, specifically in context of hepatitis virus C (HCV) and HIV. The current treatment of hepatitis C consists of a combination of drugs, of which ribavirin...

  19. Therapeutic performances of some selected aqua drugs

    Rasheduzzaman Khan Dipu

    2014-08-01

    Full Text Available This study was carried out at the Disease Laboratory of the Faculty of Fisheries, Bangladesh Agricultural University, Mymensingh, Bangladesh to verify the therapeutic performances of six commercial aqua drugs; three doses were selected as less than recommended, recommended and more than recommended to assess their performances. Before starting therapeutic experimental nine climbing perch (Anabas testudineus and six stinging catfish (Heteropneustes fossilis were confirmed as diseased ones by their clinical signs. The backswimmers (Notonecta glauca were collected from faculty of fisheries pond and fish louses (Argulus sp. were collected from tilapia fishes. Effective doses and their performances were determined on the basis of desired water quality change and clinical signs. It was found that all the drugs performed better at more than recommended doses as follows Aqua Ox performed better at the rate of 0.2 mg/l, GR Plus, 0.0005 ml/l, ID Plus (5%, 0.00026 ml/l; Active Blue, 0.0002 ml/l; Hashpoka Killer, 0.0001 ml/l; and Para Control, 0.001 ml/l. So these doses were suggested as recommended doses.

  20. Therapeutic potential of atmospheric neutrons

    Background: Glioblastoma multiform (GBM) is the most common and most aggressive type of primary brain tumour in humans. It has a very poor prognosis despite multi-modality treatments consisting of open craniotomy with surgical resection, followed by chemotherapy and/or radiotherapy. Recently, a new treatment has been proposed - Boron Neutron Capture Therapy (BNCT) - which exploits the interaction between Boron-10 atoms (introduced by vector molecules) and low energy neutrons produced by giant accelerators or nuclear reactors. Methods: The objective of the present study is to compute the deposited dose using a natural source of neutrons (atmospheric neutrons). For this purpose, Monte Carlo computer simulations were carried out to estimate the dosimetric effects of a natural source of neutrons in the matter, to establish if atmospheric neutrons interact with vector molecules containing Boron-10. Results: The doses produced (an average of 1 micro Gy in a 1 g tumour) are not sufficient for therapeutic treatment of in situ tumours. However, the non-localised yet specific dosimetric properties of 10B vector molecules could prove interesting for the treatment of micro-metastases or as (neo)adjuvant treatment. On a cellular scale, the deposited dose is approximately 0.5 Gy/neutron impact. Conclusion: It has been shown that BNCT may be used with a natural source of neutrons, and may potentially be useful for the treatment of micro-metastases. The atmospheric neutron flux is much lower than that utilized during standard NBCT. However the purpose of the proposed study is not to replace the ordinary NBCT but to test if naturally occurring atmospheric neutrons, considered to be an ionizing pollution at the Earths surface, can be used in the treatment of a disease such as cancer. To finalize this study, it is necessary to quantify the biological effects of the physically deposited dose, taking into account the characteristics of the incident particles (alpha particle and Lithium

  1. Engineering antibody therapeutics.

    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

  2. Review of data and methods recommended in the international code of practice for dosimetry IAEA Technical Reports Series No. 381, The Use of Plane Parallel Ionization Chambers in High Energy Electron and Photon beams. Final report of the co-ordinated research project on dose determination with plane parallel ionization chambers in therapeutic electron and photon beams

    In 1987 the IAEA published a Code of Practice entitled ''Absorbed Dose Determination in Photon and Electron Beams: An International Code of Practice'' (IAEA Technical Reports Series No. 277), to advise users on how to obtain the absorbed dose in water from measurements made with an ionization chamber, calibrated in terms of air kerma. The Code of Practice described procedures and provided data for the use of ionization chambers to obtain the absorbed dose in high energy photon and electron beams. It was so designed that a variety of cylindrical chambers could be used, which represented the existing conditions worldwide. However, most national and international dosimetry protocols recognized the advantages of plane parallel ionization chambers, explicitly for electron beams and especially for low energy electron beams (below 10 MeV). Although this was acknowledged in TRS-277, recommended procedures for the calibration and use of these chambers were not fully developed. Another Code of Practice entitled ''The Use of Plane Parallel Ionization Chambers in High Energy Electron and Photon Beams: An International Code of Practice for Dosimetry'' (IAEA Technical Reports Series No. 381) was published in 1997 to update TRS-277 and complement it with respect to the area of parallel plate ionization chambers. TRS-381 describes options on how to calibrate plane parallel chambers, against air kerma or absorbed dose to water standards at 60Co gamma ray energies, in order to determine the absorbed dose to water in reference conditions. The use of these chambers to calibrate therapy electron beams, as well as to perform relative dose measurements for photon and electron beams, is included in the Code of Practice which also updates some of the data and concepts in TRS-277. It is considered that the Code of Practice TRS-381 fills the gaps that existed in TRS-277 with respect to plane parallel chambers and will result in improved accuracy in radiotherapy dosimetry when these chambers

  3. Patient dose in interventional radiology

    This paper presents the estimation of dose-area product (DAP) received by 128 patients during different interventional radiological procedures in the Hospital Universitario de Salamanca, analyzing the differences between procedures classified as either vascular, non vascular, diagnostic or therapeutic. These differences can be assessed and reference dose levels can be established as a function of the variation of those parameters. Comparisons between dose-area product values obtained from this study are made with the data from nine other patient dose surveys, although explanations for some of the differences could not be obtained in some cases. The reference values in these procedures in our centre are very high due to a great number of images, so the clinical protocol should be changed to avoid this problem. (author)

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

    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...

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

    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.

  6. Dose and dose rate monitor

    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.)

  7. Optimizing lithium dosing in hemodialysis

    Bjarnason, N H; Munkner, R; Kampmann, J P; Tornoe, C W; Ladefoged, Susanne; Dalhoff, K

    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...... loading dose 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...

  8. Predictive performance of gentamicin dosing nomograms

    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

  9. Dependence of therapeutic gain factor on stage of oral cancer

    To achieve therapeutic gain, unconventional dose per fraction has been employed in radiotherapy, in addition to the conventional dose per fraction of 2 Gy. Dose fractionation factor (DFF) and therapeutic gain factor (TGF) have been utilised to test the efficiency of such unconventional fractionation schedules. In this study, isoeffective dose for 100% tumour regression and mucosal and skin reactions were estimated. CRE, TDF and ERD values for tumour and normal tissue reactions were evaluated. DEF and TGF values have been determined on the basis of dose, CRE, TDF and ERD, in order to understand the influence of these bioeffect models and stage of cancer on TGF associated with differing fractionation schedules. There was a noticeable difference in TGF values determined on the basis of four criteria, which is in agreement with radiobiological phenomenon, that tissues with different α/β values differ in their responsiveness. (author)

  10. Ondansetron. Therapeutic use as an antiemetic

    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.

  11. Ondansetron. Therapeutic use as an antiemetic

    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

  12. Lymphedema and Therapeutic Lymphangiogenesis

    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.

  13. Therapeutic HIV Peptide Vaccine

    Fomsgaard, Anders

    2015-01-01

    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...... 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...

  14. 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

    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

  15. Therapeutic Recombinant Monoclonal Antibodies

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  16. Emerging therapeutic options for asthma.

    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

  17. Acompanhamento laboratorial da função renal de cães sadios tratados experimentalmente com doses terapêuticas de anfotericina B Laboratorial accompaniment of kidney funtion of health dogs experimentally treated with therapeutic dosages of amphotericin B

    Flávia Santin

    2006-12-01

    Full Text Available O presente trabalho objetivou avaliar a função renal de dez cães adultos saudáveis submetidos à administração de doses terapêuticas do antifúngico anfotericina B, cuja utilização tem sido limitada pelo seu elevado potencial nefrotóxico, e avaliar o método laboratorial mais sensível e precoce de diagnóstico de lesão renal. Foram realizadas, diariamente, urinálise, excreção fracionada de sódio e potássio, dosagem sérica de creatinina e uréia e atividade urinária de gama-glutamiltransferase (GGT. Concluiu-se que a anfotericina B provoca lesões nos túbulos proximal e distal, induzindo acidose tubular renal do tipo I e Diabetes insipidus nefrogênico em cães. Avaliação da função renal, preferencialmente por dosagens de creatinina, uréia e potássio séricos, é recomendada antes de cada aplicação do fármaco. A densidade urinária foi o parâmetro mais precocemente alterado pela lesão renal. A GGT urinária não foi eficaz para o diagnóstico precoce de lesão induzida por anfotericina B.The objective of this experiment was to assess the renal function of ten healthy male adult dogs submitted to therapeutic doses of amphotericin B, whose use has been limited due to its high nephrotoxic potential, as well as to evaluate the more sensitive and early method to diagnose kidney lesions. The renal function was evaluated through daily urinalysis, fractioned excretion of sodium and potassium, serum concentration of creatinine and blood urea nitrogen (BUN and urinary activity of gamma-glutamyltransferase (GGT. It was concluded that amphotericin b provokes lesions in both proximal and distal tubules, inducing type I renal tubular acidosis and nephrogenic Diabetes insipidus in dogs. Renal function evaluation, preferably by serum creatinine, BUN and potassium dosage is recommended before each drug application. Urinalysis proved to diagnose kidney lesions in its earliest stage through a modification of the density parameters

  18. Dose Adjustment- An Important Issue in Critical Care

    Dr. M. C. Joshi

    2006-01-01

    Full Text Available There is at times marked variability in drug responsiveness especially in critically ill patients admitted in the Intensive care units. In order to obtain therapeutic effectiveness with in pharmacokinetic parameters related to therapeutic dose, it is always desirable to monitor and to maintain drug dose adjustment in such a way especially in presence of organ failure like renal failure, hepatic failure or any other clinical situation necessitating Therapeutic Drug Monitoring (TDM so that one can use safe and effective drug therapy with least toxicity due to inaccurate and invalid drug doses.

  19. 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

    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:

  20. Personal dosimetry of staff involved with I-131 therapeutic procedures

    Full text: Introduction: Therapeutic doses of liquid 131l (370 MBq) and 131l MIBG (3700 MBq) are frequently used in the treatment of patients with hyperthyroidism and neuroblastoma respectively. 131l is volatile and can be inhaled and accumulate in the thyroid of personnel responsible for the dispensing and administration of doses. The aim of this study was to report and assess the radiation doses to personnel involved with liquid 131l therapeutic procedures. Materials and methods: 131l liquid dispensing and administration: The uptake of 131l in the thyroid of the physicists responsible for dispensing, and medical doctors for administration of therapeutic doses was determined with a whole body counter. 131l MIBG dispensing and administration: The radiation doses received by the subjects have been monitored using calibrated lithium fluoride thermo luminescent dosimetry (TLD) discs and a direct reading pocket dosimeter. The TLD discs have been issued and worn by the physicists and the dedicated nurses doing duty at the patient. The dedicated nurses and voluntarily comforters of the patients were also issued with pocket dosimeters to measure the whole body dose received. Results: 131l liquid dispensing and administration: The activities in the thyroid of the personnel handling the therapeutic doses of liquid 131l varied from 49Bq -1466Bq. The activity that was handled varied from 370 - 3182 MBq / week. The limit set by the ICRP for 131l uptake in the thyroid is 2 MBq. 131l MIBG dispensing and administration: The whole body radiation doses received by the caregivers of 131l MIBG therapy patients varied from 0,13-.12 mSv. The ICRP whole body limit to the public is 1 mSv per year. The physicists' whole body radiation doses varied from 0.20 - 1.18 mSv per treatment. Their hand doses varied from 0.67 - 8.85 mSv. The ICRP whole body limit for radiation workers is 20 mSv per year (- 0.4 mSv per week) while the dose to the skin (hands) should not exceed 5O0mSv per year (10m

  1. Therapeutic targeting of replicative immortality.

    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

  2. Multistage vector (MSV) therapeutics.

    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

  3. Strategies for therapeutic hypometabothermia

    Liu, Shimin; Chen, Jiang-Fan

    2012-01-01

    Although therapeutic hypothermia and metabolic suppression have shown robust neuroprotection in experimental brain ischemia, systemic complications have limited their use in treating acute stroke patients. The core temperature and basic metabolic rate are tightly regulated and maintained in a very stable level in mammals. Simply lowering body temperature or metabolic rate is actually a brutal therapy that may cause more systemic as well as regional problems other than providing protection. Th...

  4. Lymphedema and Therapeutic Lymphangiogenesis

    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...

  5. PEGylation of therapeutic proteins

    Jevsevar, Simona; Kunstelj, Menci; Gaberc Porekar, Vladka

    2010-01-01

    Abstract PEGylation has been widely used as a post-production modification methodology for improving biomedical efficacy and physicochemical properties of therapeutic proteins since the first PEGylated product was approved by Food and Drug Administration in 1990. Applicability and safety of this technology have been proven by use of various PEGylated pharmaceuticals for many years. It is expected that PEGylation as the most established technology for extension of drug residence in ...

  6. DELIVERY OF THERAPEUTIC PROTEINS

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2010-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanop...

  7. Leech Therapeutic Applications

    Abdualkader, A. M.; A M Ghawi; M Alaama; Awang, M.; Merzouk, A.

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproduct...

  8. Polycyclic peptide therapeutics.

    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

  9. Boron dose enhancement for Cf-252 brachytherapy

    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

  10. [Therapeutic activity of gemcitabine in intracranial tumors].

    Stukov, A N; Filatova, L V; Latipova, D Kh; Bespalov, V G; Belyaeva, O A; Kireeva, G S; Vasilieva, I N; Alexandrov, V A; Maidin, M A; Semenov, A L; Vershinina, S F; Markochev, A B; Abduloeva, N Kh; Chubenko, V A; Semiglazova, T Yu

    2015-01-01

    Gemcitabine is known to exert a therapeutic effect on brain tumors despite the limited permeability of the blood-brain barrier (BBB). In our experimental research single intraperitoneal (i.p.) injection of gemcitabine 25 mg/kg provided increase in median survival of mice with intracranially transplanted Ehrlich carcinoma by 41-89% (p < 0.001). In this experimental model i.p. administration of gemcitabine (permeability of the BBB of less than 10%), carmustine (good permeability of the BBB), cyclophosphamide (poor permeability of the BBB) and cisplatin (doesn't penetrate through the BBB) increased median survival of mice by 88% (p < 0.001), 59% (p = 0.001), 35% (p = 0.005) and 18% (p = 0.302) respectively. Considering strong correlation between antitumor activity of the drugs (carmustine, cyclophosphamide and cisplatin) and their permeability of the BBB, efficacy of gemcitabine in intracranial tumors could be due to its wide range of therapeutic doses. PMID:26087611

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

    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)

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

    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

  13. 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

    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.

  14. Therapeutic cloning in the mouse

    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...

  15. Person-centered Therapeutics

    Cloninger, C. Robert; Cloninger, Kevin M.

    2011-01-01

    A clinician’s effectiveness in treatment depends substantially on his or her attitude toward -- and understanding of -- the patient as a person endowed with self-awareness and the will to direct his or her own future. The assessment of personality in the therapeutic encounter is a crucial foundation for forming an effective working alliance with shared goals. Helping a person to reflect on their personality provides a mirror image of their strengths and weaknesses in adapting to life’s many c...

  16. AMUM LECTURE: Therapeutic ultrasound

    Crum, Lawrence A.

    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.

  17. Therapeutic nuclear medicine

    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.

  18. Pneumothorax following therapeutic thoracentesis

    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

  19. Mechanisms of Plasma Therapeutics

    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.

  20. Engineering therapeutic protein disaggregases

    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

  1. Therapeutic nuclear medicine

    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.

  2. Dose-dependent galactorrhea with quetiapine

    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.

  3. New horizons for therapeutic nuclear medicine in 1981

    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).

  4. New horizons for therapeutic nuclear medicine in 1981

    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.

  5. 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

    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

  6. Homocystinuria: Therapeutic approach.

    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

  7. Peripheral dose measurement with a MOSFET detector

    Butson, Martin J. [Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong (China) and Department of Medical Physics, Illawarra Cancer Care Centre, Crown St., Wollongong, NSW 2500 (Australia)]. E-mail: butsonm@iahs.nsw.gov.au; Cheung, Tsang [Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong (China); Yu, Peter K.N. [Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong (China)

    2005-04-01

    The accuracy of a MOSFET dosimetry system with respect to peripheral therapeutic doses from high-energy X-rays has been evaluated . The results have been compared with ionisation chamber measurements in the same peripheral regions of the beam. For 6 MV and 18 MV X-ray beams, the MOSFET system in the high-sensitivity mode produces reproducibility of dose measurement with relative standard deviations within 1% of the maximal dose in the beam{sub ,} if the measurement is made upto 15 cm away from the beam edge. The results have shown that the MOSFET device can adequately measure peripheral doses, which would be beneficial for in vivo dose assessments in radiotherapy.

  8. Peripheral dose measurement with a MOSFET detector

    The accuracy of a MOSFET dosimetry system with respect to peripheral therapeutic doses from high-energy X-rays has been evaluated . The results have been compared with ionisation chamber measurements in the same peripheral regions of the beam. For 6 MV and 18 MV X-ray beams, the MOSFET system in the high-sensitivity mode produces reproducibility of dose measurement with relative standard deviations within 1% of the maximal dose in the beam, if the measurement is made upto 15 cm away from the beam edge. The results have shown that the MOSFET device can adequately measure peripheral doses, which would be beneficial for in vivo dose assessments in radiotherapy

  9. Therapeutic Strategies in HCC: Radiation Modalities

    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.

  10. Radiobiological speculations on therapeutic total body irradiation

    Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or therapeutic TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.77 references

  11. Optimizing lithium dosing in hemodialysis

    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...... loading dose 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...... lithium administrated immediately postdialysis. Further observations are necessary to obtain robust long-term safety data and to optimize the monitoring schedule....

  12. Optimizing Pediatric Esmolol Dosing Using Computerized Practitioner Order Entry

    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.

  13. Dosing dilemmas in obese children.

    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. FAQ about Recreational Therapy/Therapeutic Recreation

    ... 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 ...

  15. Immunogenicity to Therapeutic Proteins: Impact on PK/PD and Efficacy

    Chirmule, Narendra; Jawa, Vibha; Meibohm, Bernd

    2012-01-01

    The development of therapeutic proteins requires the understanding of the relationship between the dose, exposure, efficacy, and toxicity of these molecules. Several intrinsic and extrinsic factors contribute to the challenges for measuring therapeutic proteins in a precise and accurate manner. In addition, induction of an immune response to therapeutic protein results in additional complexities in the analysis of the pharmacokinetic profile, toxicity, safety, and efficacy of this class of mo...

  16. New therapeutics for osteoporosis.

    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

  17. Cochlear implants: response to therapeutic irradiation

    Purpose: To determine the response of cochlear implants ('bionic ears') to therapeutic irradiation. Methods and Materials: A patient with a cochlear implant was referred for palliative cranial irradiation. As there were no published or manufacturer's data available regarding the response to radiation, implants were tested for functional changes following irradiation. Cochlear implants were supplied by Cochlear Ltd. Two units each of models CI22M, CI22M (with the second generation integrated circuit) and CI24M were irradiated with 4 MV X-rays, and an unirradiated unit of each model was used as a control. The implants were irradiated initially with 25 daily fractions to 50 Gy. To determine the response at higher doses, 10 Gy fractions were delivered to the same implants to 100 Gy, followed by a final fraction of 50 Gy (total dose 150 Gy). The implants were tested after each 10 Gy, up to 100 Gy, and at 150 Gy. Several indicators of functionality were assessed, including RF (radio frequency) link range, and stimulator output current. The radiation shielding effect of the implants was also assessed. Results: Within the dose range ≤ 50 Gy, the stimulator output current of the CI22M units was the only parameter to change. At higher doses (to 150 Gy), changes in current output continued, and gradual loss of RF link range occurred in the CI22M units. The CI24M units showed changes in output current to 100 Gy, and large changes at 150 Gy. Dose attenuation by the implants was measured at 6% for ipsilateral single field 4 MV X-rays. Conclusion: Our results suggest that patients with these cochlear implants can receive cranial irradiation with a low risk of implant failure. Changes in stimulator output current can be compensated simply by re-programming the speech map after the course of radiation treatment

  18. Clinical applications of therapeutic phlebotomy

    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

  19. Therapeutic cloning: The ethical limits

    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

  20. Leech therapeutic applications

    A M Abdualkader

    2013-01-01

    Full Text Available Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin, antiplatelet (calin, saratin, factor Xa inhibitors (lefaxin, antibacterial (theromacin, theromyzin and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20 th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial.

  1. Molecularly targeted therapeutic radiopharmaceuticals

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  2. Plasmids encoding therapeutic agents

    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.

  3. Therapeutic Cancer Vaccines.

    Ye, Zhenlong; Li, Zhong; Jin, Huajun; Qian, Qijun

    2016-01-01

    Cancer is one of the major leading death causes of diseases. Prevention and treatment of cancer is an important way to decrease the incidence of tumorigenesis and prolong patients' lives. Subversive achievements on cancer immunotherapy have recently been paid much attention after many failures in basic and clinical researches. Based on deep analysis of genomics and proteomics of tumor antigens, a variety of cancer vaccines targeting tumor antigens have been tested in preclinical and human clinical trials. Many therapeutic cancer vaccines alone or combination with other conventional treatments for cancer obtained spectacular efficacy, indicating the tremendously potential application in clinic. With the illustration of underlying mechanisms of cancer immune regulation, valid, controllable, and persistent cancer vaccines will play important roles in cancer treatment, survival extension and relapse and cancer prevention. This chapter mainly summarizes the recent progresses and developments on cancer vaccine research and clinical application, thus exploring the existing obstacles in cancer vaccine research and promoting the efficacy of cancer vaccine. PMID:27240458

  4. [Liver metastasis: therapeutic strategy].

    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

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

    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)

  6. Degradation of /sup 14/C-labelled cyfluthrin in soil and incorporation of /sup 14/C in to humus fractions as affected by wheat straw amendment and moisture conditions

    An incubation experiment was conducted in the laboratory to study the effect of moisture and wheat straw amendment on the mineralization and transformation of phenyl-/sup 14/C cyfluthrin (active ingredient of Baythroid, an insecticide manufactured by Bayer AG, Leverkusen, Germany) into different soil fractions. The treated soil was incubated at 40, 60 or 100% water holding capacity (WHC) moisture and with or without wheat straw amendment. After 18 weeks of incubation 44-58% of the cyfluthrin- /sup 14/C was lost from the soil as CO/sub 2/. Mineralization of cyflutrin was more rapid in unamended soil and lower moisture regime; the maximum being at 40% WHC. In unamended soil a higher proportion of the applied /sup 14/C was found in forms extractable with methanol (an efficient solvent of cyfluthrin). In amended soil, on the other hand, a greater proportion of the added /sup 14/C was found in bound forms i.e., fulvic acid, humic acid and humins. Transformation of cyfluthrin-/sup 14/C into stable humic compounds was more intense at lower moisture regimes. However, in all treatments, a higher proportion of bound residues extractable with alkali was present in fulvic acid fraction

  7. 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

    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)

  8. Study of effective application of 2,4-D on corn in order to control of red root Pig weed and common lambs quarters, by using of 14 C labeled Herbicide Tracer technique

    One of the suitable way to control the perennial weeds in the corn production is the application of selective herbicides. In order to study the best application time of 2,4-D to control red root weed and common lambs quarters an experiments was carried out at the Nuclear Research Center for agriculture and medicine in Karaj (2001-2002). Based on our research study, different growth stages of corn and two weeds were produced under the activity of 0.05-0.12μCi (in each 10 ml of solution), through the ad axial surface. The plants were harvested 48 hours after the treatment and divided into inoculated leaf, plant above and under the inoculated leaf. This study shows that 2-3 leaf stages of corn is the best application time of selective control of red root pig weed and common lambs quarters

  9. 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

    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).

  10. Use of radioactive glucosamine in the perfused rat liver to prepare α1-acid glycoprotein (orosomucoid) with 3H- or 14C-labelled sialic acid and N-acetylglucosamine residues

    A method was developed whereby [1-14C]glucosamine was used in a perfused rat liver system to prepare over 2 mg of α1-acid glycoprotein with highly radioactive sialic acid and glucosamine residues. The liver secreted radioactive α1-acid glycoprotein over a 4-6 h period, and this glycoprotein was purified from the perfusate by chromatography on DEAE-cellulose at pH3.6. The sialic acid on the isolated glycoprotein had a specific radioactivity of 3.1 Ci/mol, whereas the glucosamine-specific radioactivity was 4.3 Ci/mole. The latter amino-sugar residues on the isolated protein were only 13-fold less radioactive than the initially added [1-14C]glucosamine. Orosomucoid with a specific radioactivity of 31.3 μCi/mg of protein was obtainable by using [6-3H]glucosamine. Many other radioactive glycoproteins were found to be secreted into the perfusate by the liver. Thus this experimental system should prove useful for obtaining other serum glycoproteins with highly radioactive sugar moieties. (author)

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

    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

  12. Therapeutics in Huntington's Disease.

    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

  13. Human Factor in Therapeutic Relationship

    AKDOĞAN, Ramazan; Esra CEYHAN

    2011-01-01

    Therapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides\\' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynam...

  14. Clinical applications of therapeutic phlebotomy

    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

  15. Metrics for antibody therapeutics development.

    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

  16. Increase of Cisplatinum therapeutic index through optical irradiation

    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.

  17. Human Factor in Therapeutic Relationship

    Ramazan Akdogan

    2011-03-01

    Full Text Available herapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynamic/deterministic tendency also take therapist-client relationship into account seriously and stress uniqueness of interaction between two people. Being a person and a human naturally sometimes may negatively influence the relationship between the therapist and client and result in a relationship going out of the theoretical frame at times. As effective components of a therapeutic process, the factors that stem from being human include the unique personalities of the therapist and the client, their values and their attitude either made consciously or subconsciously. Literature has shown that the human-related factors are too effective to be denied in therapeutic relationship process. Ethical and theoretical knowledge can be inefficient to prevent the negative effects of these factors in therapeutic process at which point a deep insight and supervision would have a critical role in continuing an acceptable therapeutic relationship. This review is focused on the reflection of some therapeutic factors resulting from being human and development of counter transference onto the therapeutic process.

  18. Exubera. Inhale therapeutic systems.

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  19. Concept for quantifying the dose from image guided radiotherapy

    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

  20. Radiosensitizers action on Iodine 131 therapeutical effect

    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)

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

    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...

  2. Radiopharmaceuticals as therapeutic agents in medical care and treatment

    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

  3. Therapeutic Applications of Monte Carlo Calculations in Nuclear Medicine

    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 ...

  4. Attachment theory and therapeutic relationships

    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. Bioengineering Beige Adipose Tissue Therapeutics

    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 physiolog...

  6. Therapeutic Vaccines for Chronic Infections

    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.

  7. Therapeutic cloning: promises and issues

    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. Metrics for antibody therapeutics development

    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...

  9. [Therapeutic touch and anorexia nervosa].

    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

  10. Antibody Engineering and Therapeutics Conference

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A.; Burton, Dennis R.; Adams, Gregory P; Weiner, Louis M.; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Bi...

  11. From cellular doses to average lung dose

    Sensitive basal and secretory cells receive a wide range of doses in human bronchial and bronchiolar airways. Variations of cellular doses arise from the location of target cells in the bronchial epithelium of a given airway and the asymmetry and variability of airway dimensions of the lung among airways in a given airway generation and among bronchial and bronchiolar airway generations. To derive a single value for the average lung dose which can be related to epidemiologically observed lung cancer risk, appropriate weighting scenarios have to be applied. Potential biological weighting parameters are the relative frequency of target cells, the number of progenitor cells, the contribution of dose enhancement at airway bifurcations, the promotional effect of cigarette smoking and, finally, the application of appropriate regional apportionment factors. Depending on the choice of weighting parameters, detriment-weighted average lung doses can vary by a factor of up to 4 for given radon progeny exposure conditions. (authors)

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

    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. 

  13. Regulatory requirements for marketing fixed dose combinations

    B G Jayasheel

    2010-01-01

    The development of fixed-dose combinations (FDCs) is becoming increasingly important from a public health perspective. FDCs have advantages when there is an identifiable patient population for whom treatment with a particular combination of actives in a fixed ratio is safe and effective and when all of the actives contribute to the overall therapeutic effect. Such combinations of drugs are particularly useful in the management of chronic diseases. In addition, there can be real clinical benef...

  14. Effect of radioimmunoassay procedures on therapeutic drug monitoring

    Methods for the measurement of therapeutic drugs have covered every aspect of analysis from extraction to derivatization. In general, published methods were modified to shorten drug extractions and overall analysis time. The use of different standards, as well as the frequent omission of internal standards, often produced large and clinically unacceptable analytical variations. As a result, physicians would adjust drug dosages according to the physiological response to a standard dose. The introduction of radioimmunoassay techniques for the quantitation of therapeutic drugs have made a significant impact on the clinical chemistry laboratory. The similarities of the various assay methods and the technologists' familiarity with the assay protocols have produced clinically relevant results. Clinical laboratories are now able to frequently analyze a large number of samples with acceptable accuracy and precision. The esoteric test once performed infrequently is today a routine analytical assay often performed STAT. Therapeutic drug monitoring has become a major activity in many clinical laboratories

  15. Dose from radiological examinations

    Relatively high gonad doses, several hundred to one thousand mR, have been observed in case of pelvis, hip-joint, coccyx, lower abdomen and lumber examination. Dose to the ovary is especially high in barium enema and I.V.P. examinations. About 12 per cent of the 4-ray examination are high-dose. The gonad dose is relatively high in examination of abdomen and lower extremities, in infants. The dose to the eyes is especially high, 1.0 to 2.5R per exposure, in temporal bone and nasal sinuses tomography. X-ray doses have been compared with dose limits recommended by ICRP and with the gonad dose from natural radiations. The gonad dose in lumbar examination, barium enema, I.V.P. etc. is as high as the maximum permissible dose per year recommended by ICRP. Several devices have been made for dose reduction in the daily examinations: (1) separating the radiation field from the gonad by one centimeter decreases the gonad dose about one-half. (2) using sensitive screens and films. In pelvimetry and in infant hip-joint examination, the most sensitive screen and film are used. In the I.V.P. examination of adult, use of MS screen in place of FS screen decreases the dose to one-third, in combination with careful setting of radiation field, (3) use of grid increases the dose about 50 percent and the lead rubber protection (0.1mm lead equivalent) decreases the gonad dose to one-thirtieth in the spinal column examination of infant, (4) A lead protector, 1mm thickness and 2.5cm in diameter, on the eyes decreases the dose to about one-eighth in the face and nead examinations. These simple and effective methods for dose reduction. Should be carried out in as many examinations as possible in addition to observing dose limits recommended by ICRP. (Evans, J.)

  16. Microdosimetry of high LET therapeutic beams

    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)

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

    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.)

  18. Radiation dose assessment in nuclear medicine

    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)

  19. [Physiopathology of ALS: therapeutic approach].

    Bruneteau, G; Demeret, S; Meininger, V

    2004-02-01

    The finding in 1993 of a mutation of the copper zinc super oxyde dismutase (SOD1) provides a major breakthrough in the understanding of the etiopathogenic mechanism of amyotrophic lateral sclerosis. Various mechanisms are commonly implied in the motor neurons degeneration. Excitotoxicity and calcium metabolism abnormalities are one of the most frequently confirmed hypotheses. It allowed proposing riluzole which remains the only one drug proved to be active in the disease. The role of growth factors remains controversial and all therapeutic trials performed with these molecules remained negative. Oxidative stress abnormalities are demonstrated by number of studies but their direct therapeutic application remains to be demonstrated. Apoptosis and the role of mitochondria has been definitely confirmed and open a new therapeutic avenue for the next few years. PMID:15034483

  20. Therapeutic hypothermia for acute stroke

    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 of...

  1. Conflicts in the therapeutic field

    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.

  2. Reactor-produced therapeutic radioisotopes

    The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

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

    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)

  4. Dose conversion factors

    The following is discussed in this report: concepts and quantities used in calculating radiation dose from internal and external exposure. Tabulations of dose conversion factor for internal and external exposure to radionuclides. Dose conversion factors give dose per unit intake (internal) or dose per unit concentration in environment (external). Intakes of radionuclides for internal exposure and concentrations of radionuclides in environment for external exposure are assumed to be known. Intakes and concentrations are obtained, e.g., from analyses of environmental transport and exposure pathways. differences between dosimetry methods for radionuclides and hazardous chemicals are highlighted

  5. Therapeutic hypothermia for acute stroke

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

    2003-01-01

    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 of...

  6. Prediction of formulation effects on dermal absorption of topically applied ectoparasiticides dosed in vitro on canine and porcine skin using a mixture-adjusted quantitative structure permeability relationship.

    Riviere, J E; Brooks, J D; Collard, W T; Deng, J; de Rose, G; Mahabir, S P; Merritt, D A; Marchiondo, A A

    2014-10-01

    Topical application of ectoparasiticides for flea and tick control is a major focus for product development in animal health. The objective of this work was to develop a quantitative structure permeability relationship (QSPeR) model sensitive to formulation effects for predicting absorption and skin deposition of five topically applied drugs administered in six vehicle combinations to porcine and canine skin in vitro. Saturated solutions (20 μL) of (14) C-labeled demiditraz, fipronil, permethrin, imidacloprid, or sisapronil were administered in single or binary (50:50 v/v) combinations of water, ethanol, and transcutol (6 formulations, n = 4-5 replicates per treatment) nonoccluded to 0.64 cm(2) disks of dermatomed pig or dog skin mounted in flow-through diffusion cells. Perfusate flux over 24 h and skin deposition at termination were determined. Permeability (logKp), absorption, and penetration endpoints were modeled using a four-term Abrahams and Martin (hydrogen-bond donor acidity and basicity, dipolarity/polarizability, and excess molar refractivity) linear free energy QSPeR equation with a mixture factor added to compensate for formulation ingredient interactions. Goodness of fit was judged by r(2) , cross-validation coefficient, coefficients (q(2) s), and Williams Plot to visualize the applicability domain. Formulation composition was the primary determinant of permeation. Compounds generally penetrated dog skin better than porcine skin. The vast majority of permeated penetrant was deposited within the dosed skin relative to transdermal flux, an attribute for ectoparasiticides. The best QSPeR logKp model for pig skin permeation (r(2) = 0.86, q(2) s = 0.85) included log octanol/water partition coefficient as the mixture factor, while for dogs (r(2) = 0.91, q(2) s = 0.90), it was log water solubility. These studies clearly showed that the permeation of topical ectoparasiticides could be well predicted using QSPeR models that account for both the physical

  7. Patient doses in interventional cardiology

    Cardiovascular diseases are the first cause of death in Spain. The most usual procedures in interventional cardiology are coronariography and PTCA. The first is a diagnostic technique, and the second one is interventional. Our goal has been to study procedures made during the first six months in the Interventional Cardiology Unit of the Juan Ramon Jimenez Hospital (Huelva-Spain), taking into account radiation protection issues. We have studied 178 patients; 145 of them underwent coronariography, and 33 of the patients had PTCA too. Every case was analyzed taking into account technical and dosimetric parameters. We show parameters values gathered: Diagnostic techniques (valvular and non-valvular patients), and interventional techniques (coronariography and PTCA in different or in the same intervention). Higher doses were obtained with valvular patients, although the number of frames was similar. Attending to therapeutic procedures, the highest values were gotten with the 'double' interventions. Interventional procedures exceed in 60% doses gotten in diagnostic studies: this is because of the number of series and number of frames per series. Similar values obtained by other authors have been gotten. (author)

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

    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. Human Factor in Therapeutic Relationship

    Ramazan Akdogan; Esra Ceyhan

    2011-01-01

    herapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynamic...

  10. Therapeutic Drug Monitoring of Lithium

    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), an...

  11. THERAPEUTIC APPLICATIONS IN NUCLEAR MEDICINE

    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.

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

    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...

  13. Enjebi Island dose assessment

    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

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

    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.

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

    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...

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

    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...

  17. Self-Microemulsifying Drug Delivery Systems: An Attractive Strategy for Enhanced Therapeutic Profile

    Akula, Samatha; Gurram, Aravind Kumar; Devireddy, Srinivas Reddy

    2014-01-01

    Ease of administration and painless approach made oral route the most preferred. Poor oral bioavailability is pronounced with the majority of recent active ingredients because of dissolution rate limited absorption. Failure to attain intended therapeutic effect of the poor water soluble drugs by this route led to development of novel drug delivery systems which will fulfill therapeutic needs with minimum dose. Although many formulation approaches like solid dispersions, complexation, pH modif...

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

    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...

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

    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...

  20. Relationship of doses and bone uptake with dosimetric results in bone pain treatment with 188Rhenium - HEDP

    Bone pain paliation in metastases by means of bone seeking β-emitters is an accepted option and 188Rhenium - HEDP has several advantages already communicated. Increased doses and multiple doses put emphasis on dosimetric considerations, although this radiopharmaceutical is estimated to deliver comparatively low absorbed doses to bone marrow. The dosimetric results of 29 therapeutic 188Re-HEDP doses in patients with painful bone metastases are presented in comparison to administered dose amount and to bone uptake

  1. Dose-painting IMRT optimization using biological parameters

    Kim, Yusung (Dept. of Radiation Oncology, Univ. of Iowa, Iowa City (United States)); Tome, Wolfgang A. (Dept. of Human Oncology Univ. of Wisconsin, Madison (United States)), E-mail: tome@humonc.wisc.edu

    2010-11-15

    Purpose. Our work on dose-painting based on the possible risk characteristics for local recurrence in tumor subvolumes and the optimization of treatment plans using biological objective functions that are region-specific are reviewed. Materials and methods. A series of intensity modulated dose-painting techniques are compared to their corresponding intensity modulated plans in which the entire PTV is treated to a single dose level, delivering the same equivalent uniform dose (EUD) to the entire PTV. Iso-TCP and iso-NTCP maps are introduced as a tool to aid the planner in the evaluation of the resulting non-uniform dose distributions. Iso-TCP and iso-NTCP maps are akin to iso-dose maps in 3D conformal radiotherapy. The impact of the currently limited diagnostic accuracy of functional imaging on a series of dose-painting techniques is also discussed. Results. Utilizing biological parameters (risk-adaptive optimization) in the generation of dose-painting plans results in an increase in the therapeutic ratio as compared to conventional dose-painting plans in which optimization techniques based on physical dose are employed. Conclusion. Dose-painting employing biological parameters appears to be a promising approach for individualized patient- and disease-specific radiotherapy

  2. Dose-painting IMRT optimization using biological parameters

    Purpose. Our work on dose-painting based on the possible risk characteristics for local recurrence in tumor subvolumes and the optimization of treatment plans using biological objective functions that are region-specific are reviewed. Materials and methods. A series of intensity modulated dose-painting techniques are compared to their corresponding intensity modulated plans in which the entire PTV is treated to a single dose level, delivering the same equivalent uniform dose (EUD) to the entire PTV. Iso-TCP and iso-NTCP maps are introduced as a tool to aid the planner in the evaluation of the resulting non-uniform dose distributions. Iso-TCP and iso-NTCP maps are akin to iso-dose maps in 3D conformal radiotherapy. The impact of the currently limited diagnostic accuracy of functional imaging on a series of dose-painting techniques is also discussed. Results. Utilizing biological parameters (risk-adaptive optimization) in the generation of dose-painting plans results in an increase in the therapeutic ratio as compared to conventional dose-painting plans in which optimization techniques based on physical dose are employed. Conclusion. Dose-painting employing biological parameters appears to be a promising approach for individualized patient- and disease-specific radiotherapy

  3. Comparative evaluation of therapeutic radiopharmaceuticals

    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

  4. 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

    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

  5. Registration of radiation doses

    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

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

    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

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

    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

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

    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)

  9. [Therapeutic use of cannabis derivatives].

    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

  10. Translating connexin biology into therapeutics.

    Becker, David L; Phillips, Anthony R; Duft, Bradford J; Kim, Yeri; Green, Colin R

    2016-02-01

    It is 45 years since gap junctions were first described. Universities face increasing commercial pressures and declining federal funding, with governments and funding foundations showing greater interest in gaining return on their investments. This review outlines approaches taken to translate gap junction research to clinical application and the challenges faced. The need for commercialisation is discussed and key concepts behind research patenting briefly described. Connexin channel roles in disease and injury are also discussed, as is identification of the connexin hemichannel as a therapeutic target which appears to play a role in both the start and perpetuation of the inflammasome pathway. Furthermore connexin hemichannel opening results in vascular dieback in acute injury and chronic disease. Translation to human indications is illustrated from the perspective of one connexin biotechnology company, CoDa Therapeutics, Inc. PMID:26688335

  11. Sinigrin and Its Therapeutic Benefits

    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.

  12. Evaluation of radiation doses from radioactive drugs

    Radioactive new drugs are regulated by the Food and Drug Administration (FDA) in the United States. Before a new drug can be marketed it must have an approved New Drug Application (NDA). Clinical investigations of a radioactive new drug are carried out under a Notice of Claimed Investigational Exemption for a New Drug (IND), submitted to the FDA. In the review of the IND, radiation doses are projected on the basis of experimental data from animal models and from calculations based upon radiation characteristics, predicted biodistribution of the drug in humans, and activity to be administered. FDA physicians review anticipated doses and prevent clinical investigations in humans when the potential risk of the use of a radioactive substance outweighs the prospect of achieving beneficial results from the administration of the drug. In the evaluation of an NDA, FDA staff attempt to assure that the intended diagnostic or therapeutic effect is achievable with the lowest practicable radiation dose. Radiation doses from radioactive new drugs are evaluated by physicians within the FDA. Important radioactive new drugs are also evaluated by the Radiopharmaceuticals Advisory Committee. FDA also supports the Center for Internal Radiation Dosimetry at Oak Ridge, to provide information regarding in vivo distribution and dosimetry to critical organs and the whole body from radioactive new drugs. The process for evaluation of radiation doses from radioactive new drugs for protection against use of unnecessary radiation exposure by patients in nuclear medicine procedures, a

  13. Therapeutic approach to sexual abuse.

    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...

  14. Therapeutic advances in muscular dystrophy

    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. Pathogenesis and new therapeutic targets

    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...

  16. Therapeutics aspects of music education

    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...

  17. Brain plasticity-based therapeutics

    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...

  18. Brain Plasticity-Based Therapeutics

    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...

  19. DNA as Therapeutics; an Update

    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...

  20. Therapeutic options for severe asthma

    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...