Sample records for half-life effective

  1. Effect of parent and daughter deformation on half-life time in exotic decay

    K P Santhosh; Antony Joseph


    Taking Coulomb and proximity potential as interacting barrier for post-scission region we calculated half-life time for different modes of exotic decay treating parent and fragments as spheres and these values are compared with experimental data. We studied the effect of deformation of parent and daughter on half-life time treating emitted cluster as spherical. When deformations are included half-life time values are found to decrease, though slightly. It is found that parent deformation alone will not produce appreciable change in half-life time since it affects relatively small pre-scission part of the barrier.

  2. Effect of parent and daughter deformation on half-life time in exotic decay

    Santhosh, K P


    Taking Coulomb and proximity potential as interacting barrier for post-scission region we calculated half-life time for different modes of exotic decay treating parent and fragments as spheres and these values are compared with experimental data. We studied the effect of deformation of parent and daughter on half-life time treating emitted cluster as spherical. When deformations are included half-life time values are found to decrease, though slightly. It is found that parent deformation alone will not produce appreciable change in half-life time since it affects relatively small pre-scission part of the barrier. (author)

  3. Liposomal Formulation of Bevasizuamb for Intravitreal Administration: Increased Half-Life, Decreased Side Effects

    Siamak Zarei Ghanavati


    Full Text Available Intravitreal injection is the common method for treatment of the posterior segment eye diseases. The advantage of intravitreal injection is achieving the desired concentration of drug inside the eye and reduction of drug side effects. Unfortunately, repeated intravitreal injections can cause several ocular complications including; vitreous hemorrhage, endophthalmitis, retinal detachment and cataract. For this reason, it seems the usage of sustained release drug delivery systems is helpful. Bevacizumab (Avastin®, antivascular endothelial growth factor (VEGF monoclonal antibody, is used for the treatment of different ocular diseases such as neovascular age-related macular degeneration, neovascular glaucoma, diabetic retinopathy, retinal vein occlusions, etc. For reduction of drug side effects and improvement of drug half-life after intravitreal administration, we suggest preparation of liposomal bevacizumab as novel drug delivery system and comparison of this new formulation with conventional formulation in the market.

  4. Effective Half-Life of Caesium-137 in Various Environmental Media at the Savannah River Site

    Paller, M. H.; Jannik, G. T.; Baker, R. A.


    During the operational history of the Savannah River Site (SRS), many different radionuclides have been released from site facilities into the SRS environment. However, only a relatively small number of pathways, most importantly 137Cs in fish and deer, have contributed significantly to doses and risks to the public. The “effective” half-lives (Te) of 137Cs (which include both physical decay and environmental dispersion) in Savannah River floodplain soil and vegetation and in fish and white-tailed deer from the SRS were estimated using long-term monitoring data. For 1974–2011, the Tes of 137Cs in Savannah River floodplain soil and vegetation were 17.0 years (95% CI = 14.2–19.9) and 13.4 years (95% CI = 10.8–16.0), respectively. These Tes were greater than in a previous study that used data collected only through 2005 as a likely result of changes in the flood regime of the Savannah River. Field analyses of 137Cs concentrations in deer collected during yearly controlled hunts at the SRS indicated an overall Te of 15.9 years (95% CI = 12.3–19.6) for 1965–2011; however, the Te for 1990–2011 was significantly shorter (11.8 years, 95% CI = 4.8–18.8) due to an increase in the rate of 137Cs removal. The shortest Tes were for fish in SRS streams and the Savannah River (3.5–9.0 years), where dilution and dispersal resulted in rapid 137Cs removal. Long-term data show that Tes are significantly shorter than the physical half-life of 137Cs in the SRS environment but that they can change over time. Therefore, it is desirable have a long period of record for calculating Tes and risky to extrapolate Tes beyond this period unless the processes governing 137Cs removal are clearly understood.

  5. Direct Deposition Effect on the Distribution of Radiocesium in Persimmon Trees and the Effective Half-life

    Tagami, Keiko; Uchida, Shigeo [National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-7444 (Japan)


    Radiocesium ({sup 137}Cs) concentrations in persimmon tree tissues collected at Chiba, about 220 km south from Fukushima Daiichi nuclear power plant (FDNPP), were measured to obtain half-life of radiocesium in the trees. Persimmon (Diospyros kaki) is a deciduous tree and bears edible fruits in autumn. There were no leaves when the sampling area was received the radioactive fallout in March 2011 due to the FDNPP accident; the amount of {sup 137}Cs radioactivity in this area was ca. 13 kBq/m{sup 3} Both {sup 137}Cs and {sup 134}Cs were found in the newly emerged shoots of the persimmon trees collected at 26 April 2011 mainly due to foliar uptake. The concentrations were 1.1 kBq/kg-dry for {sup 137}Cs and 1.3 kBq/kg-dry for {sup 134}Cs. After that, continuous sampling of leaves, branches and fruits of the persimmon trees had been carried out for two years. Immediately after the collection, samples were transferred to our laboratory and weighed to obtain fresh weight. Leaf samples were usually separated into two portions; one portion was washed with tap water to remove dust from the surface and the other portion was not treated. For fruit samples, if it is possible, fruit flesh, peal and non-edible part were separated. All the samples were oven-dried at 80 deg. C for three days at least. Each dried sample was chopped into fine pieces, mixed well, and then transferred into plastic vessels separately. Radioactivity concentration was measured by a Ge-detecting system (Seiko EG and G Ortec) using 3000-40000 s counting intervals. By August 14, 2013, about 140 samples were collected from the trees; about 60 samples were leaves (both washed and untreated). Radiocesium concentrations in tree leaves decreased with time, and the effective half-life was about 190 d; the value was similar to those in branches (160 d for new branches, and 250 d for 1-2 y.o. branches) and fruits (250 d for fruit flesh and 230 d for peals). Thus we concluded that the half-life of radiocesium in

  6. Improved in vivo anti-tumor effects of IgA-Her2 antibodies through half-life extension and serum exposure enhancement by FcRn targeting.

    Meyer, Saskia; Nederend, Maaike; Jansen, J H Marco; Reiding, Karli R; Jacobino, Shamir R; Meeldijk, Jan; Bovenschen, Niels; Wuhrer, Manfred; Valerius, Thomas; Ubink, Ruud; Boross, Peter; Rouwendal, Gerard; Leusen, Jeanette H W


    Antibody therapy is a validated treatment approach for several malignancies. All currently clinically applied therapeutic antibodies (Abs) are of the IgG isotype. However, not all patients respond to this therapy and relapses can occur. IgA represents an alternative isotype for antibody therapy that engages FcαRI expressing myeloid effector cells, such as neutrophils and monocytes. IgA Abs have been shown to effectively kill tumor cells both in vitro and in vivo. However, due to the short half-life of IgA Abs in mice, daily injections are required to reach an effect comparable to IgG Abs. The relatively long half-life of IgG Abs and serum albumin arises from their capability of interacting with the neonatal Fc receptor (FcRn). As IgA Abs lack a binding site for FcRn, we generated IgA Abs with the variable regions of the Her2-specific Ab trastuzumab and attached an albumin-binding domain (ABD) to the heavy or light chain (HCABD/LCABD) to extend their serum half-life. These modified Abs were able to bind albumin from different species in vitro. Furthermore, tumor cell lysis of IgA-Her2-LCABD Abs in vitro was similar to unmodified IgA-Her2 Abs. Pharmacokinetic studies in mice revealed that the serum exposure and half-life of the modified IgA-Her2 Abs was extended. In a xenograft mouse model, the modified IgA1 Abs exhibited a slightly, but significantly, improved anti-tumor response compared to the unmodified Ab. In conclusion, empowering IgA Abs with albumin-binding capacity results in in vitro and in vivo functional Abs with an enhanced exposure and prolonged half-life.

  7. A novel exendin-4 human serum albumin fusion protein, E2HSA, with an extended half-life and good glucoregulatory effect in healthy rhesus monkeys

    Zhang, Ling; Wang, Lin; Meng, Zhiyun; Gan, Hui; Gu, Ruolan; Wu, Zhuona; Gao, Lei; Zhu, Xiaoxia; Sun, Wenzhong; Li, Jian; Zheng, Ying; Dou, Guifang, E-mail:


    Highlights: • E2HSA has an extended half-life and good plasma stability. • E2HSA could improve glucose-dependent insulin secretion. • E2HSA has excellent glucoregulatory effects in vivo. • E2HSA could potentially be used as a new long-acting GLP-1 receptor agonist for type 2 diabetes management. - Abstract: Glucagon-like peptide-1 (GLP-1) has attracted considerable research interest in terms of the treatment of type 2 diabetes due to their multiple glucoregulatory functions. However, the short half-life, rapid inactivation by dipeptidyl peptidase-IV (DPP-IV) and excretion, limits the therapeutic potential of the native incretin hormone. Therefore, efforts are being made to develop the long-acting incretin mimetics via modifying its structure. Here we report a novel recombinant exendin-4 human serum albumin fusion protein E2HSA with HSA molecule extends their circulatory half-life in vivo while still retaining exendin-4 biological activity and therapeutic properties. In vitro comparisons of E2HSA and exendin-4 showed similar insulinotropic activity on rat pancreatic islets and GLP-1R-dependent biological activity on RIN-m5F cells, although E2HSA was less potent than exendin-4. E2HSA had a terminal elimation half-life of approximate 54 h in healthy rhesus monkeys. Furthermore, E2HSA could reduce postprandial glucose excursion and control fasting glucose level, dose-dependent suppress food intake. Improvement in glucose-dependent insulin secretion and control serum glucose excursions were observed during hyperglycemic clamp test (18 h) and oral glucose tolerance test (42 h) respectively. Thus the improved physiological characterization of E2HSA make it a new potent anti-diabetic drug for type 2 diabetes therapy.

  8. The effective and environmental half-life of {sup 137}Cs at Coral Islands at the former US nuclear test site

    Robison, William L. E-mail:; Conrado, Cynthia L.; Bogen, Kenneth T.; Stoker, A. Carol


    The United States (US) conducted nuclear weapons testing from 1946 to 1958 at Bikini and Enewetak Atolls in the northern Marshall Islands. Based on previous detailed dose assessments for Bikini, Enewetak, Rongelap, and Utirik Atolls over a period of 28 years, cesium-137 ({sup 137}Cs) at Bikini Atoll contributes about 85-89% of the total estimated dose through the terrestrial food chain as a result of uptake of {sup 137}Cs by food crops. The estimated integral 30, 50, and 70-year doses were based on the radiological decay of {sup 137}Cs (30-year half-life) and other radionuclides. However, there is a continuing inventory of {sup 137}Cs and {sup 90}Sr in the fresh water portion of the groundwater at all contaminated atolls even though the turnover rate of the fresh groundwater is about 5 years. This is evidence that a portion of the soluble fraction of {sup 137}Cs and {sup 90}Sr inventory in the soil is lost by transport to groundwater when rainfall is heavy enough to cause recharge of the lens, resulting in loss of {sup 137}Cs from the soil column and root zone of the plants. This loss is in addition to that caused by radioactive decay. The effective rate of loss was determined by two methods: (1) indirectly, from time-dependent studies of the {sup 137}Cs concentration in leaves of Pisonia grandis, Guettarda specosia, Tournefortia argentea (also called Messerschmidia), Scaevola taccada, and fruit from Pandanus and coconut trees (Cocos nucifera L.), and (2) more directly, by evaluating the {sup 137}Cs/{sup 90}Sr ratios at Bikini Atoll. The mean (and its lower and upper 95% confidence limits) for effective half-life and for environmental-loss half-life (ELH) based on all the trees studied on Rongelap, Bikini, and Enewetak Atolls are 8.5 years (8.0 years, 9.8 years), and 12 years (11 years, 15 years), respectively. The ELH based on the {sup 137}Cs/{sup 90}Sr ratios in soil in 1987 relative to the{sup 137}Cs/{sup 90}Sr ratios at the time of deposition in 1954 is less

  9. Effect of Truncating AUC at 12, 24 and 48 hr When Evaluating the Bioequivalence of Drugs with a Long Half-Life.

    Moreno, Isabel; Ochoa, Dolores; Román, Manuel; Cabaleiro, Teresa; Abad-Santos, Francisco


    Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalent.

  10. Half Life Measurements in {sup 155}Gd

    Malmskog, S.G.


    In the literature there exists a definite difference for the half life of the 86.5 keV level in Gd depending on whether {sup 155}Eu or {sup 155}Tb sources have been used. Using a good energy resolution electron-electron coincidence spectrometer and a {sup 155}Eu source, a half life of 6.48 {+-} 0.26 nsec was obtained for the 86.5 keV level. This is in agreement with the values previously measured with {sup 155}Tb sources. The half life of the 105.4 keV level was measured to be 1.12 {+-} 0.05 nsec.

  11. Half-life of {sup 44}Ti

    Ahmad, I.; Kutschera, W.; Castagnoli, G. [Instituto di Cosmogeofisica, Torino (Italy); Paul, M. [Hebrew Univ., Jerusalem (Israel)


    The measurement of the {sup 44}Ti half-life, started 3 years ago, is still continuing. The goal of this measurement is to determine the half-life of {sup 44}Ti, which is {approximately}52 y, to a precision of {approximately}5%. An accurate value of this half-life is of interest to cosmologists who need it to determine the production of heavy elements in supernova. Three sets of samples - a pure 200-nCi {sup 44}Ti sample, a pure 300-nCi {sup 60}Co source, and a mixed {sup 44}Ti-{sup 60}Co source of similar strength - were prepared and their spectra are being measured with Ge spectrometers at Argonne, Torino and Jerusalem. Each sample is counted for a period of 2 days, at approximate intervals of 4 months. The room background is also measured for the same length of time. We hope to start data analysis at the end of summer and obtain a value for the {sup 44}Ti half-life.

  12. Half-life of 51Mn

    Graves, Stephen A.; Ellison, Paul A.; Valdovinos, Hector F.; Barnhart, Todd E.; Nickles, Robert J.; Engle, Jonathan W.


    The half-life of 51Mn was measured by serial gamma spectrometry of the 511-keV annihilation photon following decay by β+ emission. Data were collected every 100 seconds for 100,000-230,000 seconds within each measurement (n =4 ). The 511-keV incidence rate was calculated from the 511-keV spectral peak area and count duration, corrected for detector dead time and radioactive decay. Least-squares regression analysis was used to determine the half-life of 51Mn while accounting for the presence of background contaminants, notably 55Co. The result was 45.59 ±0.07 min, which is the highest precision measurement to date and disagrees with the current Nuclear Data Sheets value by over 6 σ .

  13. Half-life of samarium-147

    Kinoshita, N; Nakanishi, T


    The alpha-decay half-life of sup 1 sup 4 sup 7 Sm has been reevaluated. Known amounts of natural Sm and an alpha-emitter standard ( sup 2 sup 1 sup 0 Po, sup 2 sup 3 sup 8 U, or sup 2 sup 4 sup 1 Am) were mixed well to prepare thin sources for the simultaneous counting of sup 1 sup 4 sup 7 Sm and the alpha-emitter standard by means of an alpha-spectrometer using a silicon surface barrier detector. The alpha-disintegration rate of known amounts of sup 1 sup 4 sup 7 Sm was determined by reference to the alpha activity of the standard. The source preparation and counting were repeated to establish the reproducibility of the present half-life determination, and supplementary alpha spectrometry was carried out by a liquid-scintillation spectrometer. The arithmetic mean of the experimental half-life values was obtained to be (1.17 +- 0.02) x 10 sup 1 sup 1 y. This value is about 10% longer than the currently adopted value, (1.06 +- 0.02) x 10 sup 1 sup 1 y, and the possible factors for this difference are discussed...

  14. The half-life of 18F.

    García-Toraño, Eduardo; Medina, Virginia Peyrés; Ibarra, Miguel Roteta


    The half-life of the positron-emitter (18)F has been measured by following the decay rate with three systems: ionization chambers, Ge detectors and coincidence with fast scintillators. The decay rate was measured for periods of time up to 9 half-lives. The combination of the results obtained with the three measuring systems gives a value of T(1/2)=1.82871 (18)h, in good agreement with recommended data and with an estimated uncertainty lower than any other previously reported value. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Half-life predictions for decay modes of superheavy nuclei

    Duarte, S.B.; Tavares, O.A.P. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Goncalves, M. [Instituto de Radioprotecao e Dosimetria (IRD), Rio de Janeiro, RJ (Brazil); Rodriguez, O.; Guzman, F. [Instituto Superior de Ciencias e Tecnologia Nucleares (InSTEC), La Habana (Cuba); Barbosa, T.N.; Garcia, F.; Dimarco, A. [Universidade Estadual de Santa Cruz, Ilheus, BA (Brazil). Dept. de Ciencias Exatas e Tecnologicas


    We applied the Effective Liquid Drop Model (ELDM) to predict the alpha-decay, cluster emission and cold fission half-life-values of nuclei in the region of Superheavy Elements (SHE). The present calculations have been made in the region of the ZN-plane defined by 155 <=N <=220 and 110<=Z<=135. Shell effects are included via the Q-value of the corresponding decay case. We report the results of a systematic calculation of the half-life for the three nuclear decay modes in a region of the ZN-plane where superheavy elements are expected to be found. Results have shown that, among the decay modes investigated here, the alpha decay is the dominant one. i.e, the decay mode of smallest half-lives. Half-life predictions for alpha decay, cluster emission and cold fission for the isotopic family of the most recent SHE detected of Z=115 and for the isotopic family of the already consolidated SHE of Z=111 are presented. (author)

  16. Meta-analysis of on-the-road experimental studies of hypnotics : effects of time after intake, dose, and half-life

    Roth, T; Eklov, S D; Drake, C L; Verster, J C


    BACKGROUND: The use of hypnotics is prevalent in the general population. Though these drugs have been shown to be effective, their residual effects may cause significant impairment to the user's driving ability. The objective of this meta-analysis is to determine whether there is a residual effect

  17. Meta-analysis of on-the-road experimental studies of hypnotics : effects of time after intake, dose, and half-life

    Roth, T; Eklov, S D; Drake, C L; Verster, J C


    BACKGROUND: The use of hypnotics is prevalent in the general population. Though these drugs have been shown to be effective, their residual effects may cause significant impairment to the user's driving ability. The objective of this meta-analysis is to determine whether there is a residual effect o

  18. Half-life of 31Si

    D'Agostino, Giancarlo; Mana, Giovanni; Oddone, Massimo


    Half-life values are widely used in nuclear chemistry to model the exponential decay of the quantified radionuclides. The analysis of existing data reveals a general lack of information on the performed experiments and an almost complete absence of uncertainty budgets. This is the situation for 31Si, the radionuclide produced via neutron capture reaction recently used to quantify trace amounts of 30Si in a sample of the silicon material highly enriched in 28Si and used for the determination of the Avogadro constant. In order to improve the quality of the now recommended 157.36(26) min value, we carried out repeated observations of the 31Si decay rate via gamma-ray spectrometry measurements. This paper reports the result we obtained, including details of the experiment and the evaluation of the uncertainty.

  19. Estimation of the Biological Half-Life of Methylmercury Using a Population Toxicokinetic Model

    Seongil Jo


    Full Text Available Methylmercury is well known for causing adverse health effects in the brain and nervous system. Estimating the elimination constant derived from the biological half-life of methylmercury in the blood or hair is an important part of calculating guidelines for methylmercury intake. Thus, this study was conducted to estimate the biological half-life of methylmercury in Korean adults. We used a one-compartment model with a direct relationship between methylmercury concentrations in the blood and daily dietary intake of methylmercury. We quantified the between-person variability of the methylmercury half-life in the population, and informative priors were used to estimate the parameters in the model. The population half-life of methylmercury was estimated to be 80.2 ± 8.6 days. The population mean of the methylmercury half-life was 81.6 ± 8.4 days for men and 78.9 ± 8.6 days for women. The standard deviation of the half-life was estimated at 25.0 ± 8.6 days. Using the direct relationship between methylmercury concentrations in blood and methylmercury intake, the biological half-life in this study was estimated to be longer than indicated by the earlier studies that have been used to set guideline values.

  20. Investigation of temperature effect on half-life periods of long-lived isomer sup 1 sup 8 sup 0 sup m Hf and sup 8 sup 7 sup m Sr

    Alpatov, V G; Davydov, A V; Isaev, Y N; Kartashov, G R; Korotkov, M M; Samojlov, V M


    The experiments on measuring the half-life periods of the sup 1 sup 8 sup 0 sup m Hf and sup 8 sup 7 sup m Sr long-lived isomers at the room temperature and at 77 K with application of the HfO sub 2 , Sr(NO sub 3) sub 2 and SrCO sub 3 massive samples are described. The isomer states of the corresponding nuclei were formed by the samples irradiation through neutrons from the Pu-Be source. According to the Vysotski theory and other authors the surrounding of the gamma-active nuclei by a large number of the same nuclei in the basic state should lead to the T sub 1 sub / sub 2 growth due to distortion of the zero electromagnetic vacuum oscillations near the nuclear energy level value. Decrease in the sample temperature leads to the narrowing of the gamma-lines, especially for the Moessbauer low-energy transitions, which increases the resonance effect on the zero oscillations spectrum. Increase in the T sub 1 sub / sub 2 by 2.99 +- 0.87% was observed by cooling the sup 1 sup 8 sup 0 sup m Hf isomer sample, in the ...

  1. PEGylation of antibody fragments for half-life extension.

    Jevševar, Simona; Kusterle, Mateja; Kenig, Maja


    Antibody fragments (Fab's) represent important structure for creating new therapeutics. Compared to full antibodies Fab' fragments possess certain advantages, including higher mobility and tissue penetration, ability to bind antigen monovalently and lack of fragment crystallizable (Fc) region-mediated functions such as antibody-dependent cell mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). The main drawback for the use of Fab's in clinical applications is associated with their short half-life in vivo, which is a consequence of no longer having the Fc region. To exert meaningful clinical effects, the half-life of Fab's need to be extended, which has been achieved by postproduction chemical attachment of polyethylene glycol (PEG) chain to protein using PEGylation technology. The most suitable approach employs PEG-maleimide attachment to cysteines, either to the free hinge cysteine or to C-terminal cysteines involved in interchain disulfide linkage of the heavy and light chain. Hence, protocols for mono-PEGylation of Fab via free cysteine in the hinge region and di-PEGylation of Fab via interchain disulfide bridge are provided in this chapter.

  2. Influence of sex and age on the biological half-life of cadmium in mice

    Taguchi, T. (Kochi Medical School, Nangoku-shi, Japan); Suzuki, S.


    The influence of age on the whole-body biological half-life of /sup 109/Cd was studied in male mice following ip injection. The influence of sex on whole-body and organ retention was ascertained after sc injection. The whole-body biological half-life of /sup 109/Cd of the older mice was more than twice that of the younger mice, and that of the female mice was longer than that of the males. These differences demonstrate a biological difference between males and females with respect to whole-body half-life of /sup 109/Cd. The effects of age and sex on the biological half-life of Cd in mice are assessed quantitatively.

  3. Calculation of half-life for 79Se decay


    The half-life for 79Se decay is calculated by using the Logf1ut systematics method. Based on the data analysis and comparison with experimental data the 79Se half-life is recommended. The scheme for 79Se decay is also shown and the radiation data are calculated in the text.

  4. The Result of Multiple I-131 Treatments on the Effective Half-Life of Retained Radioactivity in Patients Ablated for Differentiated Thyroid Cancer: Possible Evidence for Thyroid Remnant Function Impairment.

    Okkalides, Demetrios


    The ablation of differentiated thyroid cancer by ingested I-131 depends on the activity absorbed by the remnant. This depends on the function of the thyroid cells and on the rate that radioactivity is excreted from the blood. The reduction of radioiodine is described by the effective half-life (EHL), which is the time taken to half the retained radioactivity. If the tumor recurs, more treatments are prescribed, often with escalating activities. Patients may receive several treatments during the evolution of the disease, and the total radioactivity administered (TRA) is the sum of all such activities. The patients' archived information permitted the calculation of EHL and TRA. The patient cohort processed here comprised 274 females and 101 males treated during 1997 to 2015. The TRA to the patients ranged between 1.1 and 129.5 GBq (average = 7.93 ± 9.9 GBq) and the EHL varied between 5.06 and 43.87 hours (average = 14.13 ± 5.7 hours). The data were processed as follows: (a) the EHL corresponding to the last treatment of each patient was plotted against TRA to patients who were treated once and to those treated several times for comparison and (b) using a small subgroup of 16 patients who were treated at least 5 times, the EHL and TRA corresponding to each treatment of each patient were plotted. A function of the form y = p-k·ln(x) was fitted on the data in all graphs and k was calculated. For patients treated once, EHL was independent of TRA. A decrease was seen in (a) multitreated patients, with the gradient (k) ranging between -0.541 and -13.880 and (b) 13 out of 16 patients, with the gradient (k) ranging between -5.55 and -31.17, both indicating an impairment of the remnant function, perhaps identified as "stunning." Since this is not avoidable, the uptake may be boosted by splitting the prescribed activity into low radioactivity fractions, which will also reduce patient hospitalization.

  5. PEPlife: A Repository of the Half-life of Peptides

    Mathur, Deepika; Prakash, Satya; Anand, Priya; Kaur, Harpreet; Agrawal, Piyush; Mehta, Ayesha; Kumar, Rajesh; Singh, Sandeep; Raghava, Gajendra P. S.


    Short half-life is one of the key challenges in the field of therapeutic peptides. Various studies have reported enhancement in the stability of peptides using methods like chemical modifications, D-amino acid substitution, cyclization, replacement of labile aminos acids, etc. In order to study this scattered data, there is a pressing need for a repository dedicated to the half-life of peptides. To fill this lacuna, we have developed PEPlife (, a manually curated resource of experimentally determined half-life of peptides. PEPlife contains 2229 entries covering 1193 unique peptides. Each entry provides detailed information of the peptide, like its name, sequence, half-life, modifications, the experimental assay for determining half-life, biological nature and activity of the peptide. We also maintain SMILES and structures of peptides. We have incorporated web-based modules to offer user-friendly data searching and browsing in the database. PEPlife integrates numerous tools to perform various types of analysis such as BLAST, Smith-Waterman algorithm, GGSEARCH, Jalview and MUSTANG. PEPlife would augment the understanding of different factors that affect the half-life of peptides like modifications, sequence, length, route of delivery of the peptide, etc. We anticipate that PEPlife will be useful for the researchers working in the area of peptide-based therapeutics.

  6. Beta Decay Half-Life of 84Mo

    Stoker, J. B.; Mantica, P. F.; Bazin, D.; Bickley, A.; Becerril, A.; Crawford, H.; Cruse, K.; Estrade, A.; Mosby, M.; Guess, C. J.; Hitt, G. W.; Lorusso, G.; Matos, M.; Meharchand, R.; Minamisono, K.; Montes, F.; Pereira, J.; Perdikakis, G.; Pinter, J. S.; Schatz, H.; Vredevoogd, J.; Zegers, R. G. T.


    The β-decay half-life ^84Mo governs leakage out of the Zr-Nb cycle, a high temperature rp-process endpoint in x-ray binaries [1]. Treatment of the background and the poor statistics accumulated during the previous half-life measurement leave questions about statistical and systematic errors. We have remeasured the half-life of ^84Mo using a concerted setup of the NSCL β-Counting System [3] and 16 detectors from the Segmented Germanium Array [4]. We will report the half-life for ^84Mo, deduced using 40 times the previous sample size. The application of the NSCL RF Fragment Separator to remove unwanted isotopes, and hence reduce background for the half-life measurement, will also be discussed. [1] H. Schatz et al., Phys. Rep. 294, 167 1998 [2] P. Kienle et al., Prog. Part. Nuc. Phys. 46, 73 2001 [3] J. Prisciandaro et al., NIM A 505, 140 2003 [4] W. Mueller et al., NIM A 466, 492 2001 [5] D. Gorelov et al. PAC 2005, Knoxville, TN, May 16-20

  7. 18F half-life measurement using a high-purity germanium detector.

    Han, Jubong; Lee, K B; Park, T S; Lee, J M; Oh, P J; Lee, S H; Kang, Y S; Ahn, J K


    The half-life of (18)F has been measured using HPGe detectors with a (137)Cs reference source. The counting ratio of 511 keV γ-rays from (18)F to 622 keV γ-rays from (137)Cs was fitted for the half-life with a weighted least-square method. Uncertainties due to the systematic effects arising from the measurement of a high activity (18)F source were studied in detail. The half-life of (18)F was found to be (109.72±0.19) min. The result is in a good agreement with the recommended value of (109.728±0.019) min evaluated at the Laborotaire National Henri Becquerel (LNHB).

  8. $\\beta$-Decay Half-Life of the $rp$-Process Waiting Point Nuclide $^{84}$Mo

    Stoker, J B; Bazin, D; Becerril, A; Berryman, J S; Crawford, H L; Estrade, A; Guess, C J; Hitt, G W; Lorusso, G; Matos, M; Minamisono, K; Montes, F; Pereira, J; Perdikakis, G; Schatz, H; Smith, K; Zegers, R G T


    A half-life of 2.2 $\\pm$ 0.2 s has been deduced for the ground-state $\\beta$ decay of $^{84}$Mo, more than 1$\\sigma$ shorter than the previously adopted value. $^{84}$Mo is an even-even N = Z nucleus lying on the proton dripline, created during explosive hydrogen burning in Type I X-ray bursts in the rapid proton capture ($rp$) process. The effect of the measured half-life on $rp$-process reaction flow is explored. Implications on theoretical treatments of nuclear deformation in $^{84}$Mo are also discussed.

  9. Determination of the {sup 151}Sm half-life

    Be, Marie-Martine; Cassette, Philippe [CEA, LIST, Gif sur Yvette (France). LNE-Laboratoire National Henri Becquerel; Isnard, Helene [CEA-LANIE, Gif sur Yvette (France); and others


    New measurements have been undertaken to determine the half-life of {sup 151}Sm. A pure {sup 151}Sm solution was obtained after chemical separation from a samarium solution resulting from the dissolution of an irradiated samarium sample. The concentration of {sup 151}Sm in the solution was measured by mass spectrometry, combined with the isotope dilution technique. The activity of the solution was measured by liquid scintillation counting by six European laboratories as part of an international comparison. These combined results lead to a half-life of T{sub 1/2} = 94.6(6)a.

  10. Superior serum half life of albumin tagged TNF ligands

    Mueller, Nicole [Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wuerzburg, Roentgenring 11, 97070 Wuerzburg (Germany); Schneider, Britta; Pfizenmaier, Klaus [Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart (Germany); Wajant, Harald, E-mail: [Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wuerzburg, Roentgenring 11, 97070 Wuerzburg (Germany)


    Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

  11. The half-life of {sup 18}F

    Garcia-Torano, Eduardo, E-mail: e.garciatorano@ciemat.e [Ciemat, Laboratorio de Metrologia de Radiaciones Ionizantes, Avda. Complutense 22, Madrid 28040 (Spain); Medina, Virginia Peyres; Roteta Ibarra, Miguel [Ciemat, Laboratorio de Metrologia de Radiaciones Ionizantes, Avda. Complutense 22, Madrid 28040 (Spain)


    The half-life of the positron-emitter {sup 18}F has been measured by following the decay rate with three systems: ionization chambers, Ge detectors and coincidence with fast scintillators. The decay rate was measured for periods of time up to 9 half-lives. The combination of the results obtained with the three measuring systems gives a value of T{sub 1/2}=1.82871 (18) h, in good agreement with recommended data and with an estimated uncertainty lower than any other previously reported value.

  12. Experimental determination of the {sup 233}U half-life

    Pomme, S.; Altzitzoglou, T.; Van Ammel, R.; Sibbens, G.; Eykens, R.; Richter, S.; Camps, J. [European Commission, Joint Research Centre, Institute for Reference Materials and Measurements, Geel (Belgium); Kossert, K.; Janben, H. [Physikalisch-Technische Bundesanstalt (PTB), Braunschweig (Germany); Garcia-Torano, E.; Duran, T. [CIEMAT, Lab. de Metrologia de Radiaciones Ionizantes, Madrid (Spain); Jaubert, F. [CEA Saclay, LNE-LNHB, Lab. National Henri Becquerel 91 - Gif-sur-Yvette (France)


    The half-life of {sup 233}U was determined by a specific activity method, in the frame of an international collaboration project of four metrology institutes. A purified, highly enriched {sup 233}U solution was prepared with certified concentration of uranium isotopes. The isotopic composition of the uranium material was determined by thermal ionization mass spectrometry. The ingrowth of daughter nuclides was calculated and confirmed by {alpha}-particle and {gamma}-ray spectrometry measurements. Quantitative sources were prepared from aliquots of the {sup 233}U solution and their disintegration rate was determined by means of {alpha}-particle counting at a defined small solid angle, liquid-scintillation counting and 4{pi} counting in a pressurized proportional counter and in a CsI(Tl) sandwich spectrometer. A half-life value of 1.5867(14) * 10{sup 5} a was obtained, in which the relative standard uncertainty amounts to 0.09%. The result is lower than the currently recommended value of 1.592(2) * 10{sup 5} a and a new best estimate of T(1/2)({sup 233}U) = 1.5903(13) * 10{sup 5} a was calculated from a partially weighted mean of a set of published data. (authors)

  13. Half-life extended factor VIII for the treatment of hemophilia A.

    Tiede, A


    Prophylactic infusion of factor VIII (FVIII) prevents joint bleeding and other hemorrhages in patients with hemophilia A. Conventional FVIII concentrates have a short half-life, with an average of about 12 h in adults, ranging in individual patients between 6 and 24 h, and even shorter in younger children. Therefore, effective prophylaxis requires frequent intravenous injection, usually three times per week or every other day. Several technologies are currently under investigation to extend the half-life of FVIII, including Fc fusion (Eloctate, Elocta, efmoroctocog alfa), addition of polyethylene glycol (turoctocog alfa pegol [N8-GP], BAY 94-9027, BAX 855), and a single-chain construct (CSL627). This review summarizes characteristics of products in clinical development and discusses their potential benefits.

  14. A Calorimetric Determination of the Half Life of Polonium-210 (Final Report)

    Eichelberger, J. F.; Jordan, K. C.; Orr, S. R.; Parks, J. R.


    Six determinations have been made of the half life of polonium with four different steady-state, resistance-bridge calorimeters and five different samples of polonium. These six values of the half life have been weighted and combined to give a grand-mean value of the half life of 138.4005 + - 0.0051 days.

  15. A shorter 146Sm half-life measured and implications for 146Sm-142Nd chronology in the solar system.

    Kinoshita, N; Paul, M; Kashiv, Y; Collon, P; Deibel, C M; DiGiovine, B; Greene, J P; Henderson, D J; Jiang, C L; Marley, S T; Nakanishi, T; Pardo, R C; Rehm, K E; Robertson, D; Scott, R; Schmitt, C; Tang, X D; Vondrasek, R; Yokoyama, A


    The extinct p-process nuclide (146)Sm serves as an astrophysical and geochemical chronometer through measurements of isotopic anomalies of its α-decay daughter (142)Nd. Based on analyses of (146)Sm/(147)Sm α-activity and atom ratios, we determined the half-life of (146)Sm to be 68 ± 7 (1σ) million years, which is shorter than the currently used value of 103 ± 5 million years. This half-life value implies a higher initial (146)Sm abundance in the early solar system, ((146)Sm/(144)Sm)(0) = 0.0094 ± 0.0005 (2σ), than previously estimated. Terrestrial, lunar, and martian planetary silicate mantle differentiation events dated with (146)Sm-(142)Nd converge to a shorter time span and in general to earlier times, due to the combined effect of the new (146)Sm half-life and ((146)Sm/(144)Sm)(0) values.

  16. Semi-empirical formula for spontaneous fission half life time

    Santhosh, K.P., E-mail: [School of Pure and Applied Physics, Kannur University, Payyanur Campus 670 327 (India); Biju, R.K.; Sahadevan, Sabina [P G Department of Physics and Research Centre, Payyanur College, Payyanur 670 327 (India)


    A new semi-empirical formula is proposed for determining the spontaneous fission half lives, which works well for the mass region from {sup 232}Th to {sup 286}114. The computed spontaneous fission half life times are also compared with other semi-empirical formula predictions. The alpha decay half lives are systematically computed for heavy and super heavy region with proton numbers varying from 90<=Z<=122 using Coulomb and Proximity Potential Model. The comparison between computed alpha decay half lives and the present spontaneous fission semi-empirical formula predictions of even-even isotopes with Z=90-122 are studied. It is found that in super heavy region the isotopes {sup 270-274}Ds, {sup 272-278}112, {sup 272-282}114, {sup 274-292}116, {sup 276-298}118, {sup 276-308}120 and {sup 278-314}122 will survive fission and can be synthesized and identified via alpha decay.

  17. 63Ni, its half-life and standardization: revisited.

    Collé, R; Zimmerman, B E; Cassette, P; Laureano-Perez, L


    Recent liquid scintillation (LS) measurements at the National Institute of Standards and Technology (NIST) and at the Laboratoire National Henri Becquerel (LNHB) on a standardized (63)Ni solution that has been tracked for nearly 40 years have resulted in several important findings: (i) a (63)Ni half-life value of 101.2 +/- 1.5 a has been determined with the present decay data. This value is consistent with a previous specific activity determination and with an earlier value from decay measurements; and it appears to be more satisfactory than a recent data evaluator's recommended value of 98.7 a. (ii) All solution standards of (63)Ni as disseminated by NIST for the past 38(+) years are internally consistent with past and recent standardizations. (iii) Primary LS standardizations of (63)Ni by the triple-to-double coincidence ratio (TDCR) method and by CIEMAT/NIST (3)H-standard efficiency tracing (CNET) appear to be comparable, although the latter methodology is believed to be inherently inferior. (iv) There is excellent measurement agreement between NIST and LNHB for (63)Ni primary standardizations.

  18. β-decay half-life of the rp-process waiting-point nuclide Mo84

    Stoker, J. B.; Mantica, P. F.; Bazin, D.; Becerril, A.; Berryman, J. S.; Crawford, H. L.; Estrade, A.; Guess, C. J.; Hitt, G. W.; Lorusso, G.; Matos, M.; Minamisono, K.; Montes, F.; Pereira, J.; Perdikakis, G.; Schatz, H.; Smith, K.; Zegers, R. G. T.


    A half-life of 2.2 ± 0.2 s has been deduced for the ground-state β decay of Mo84, more than 1σ shorter than the previously adopted value. Mo84 is an even-even N=Z nucleus lying on the proton dripline, created during explosive hydrogen burning in type I x-ray bursts in the rapid proton capture (rp) process. The effect of the measured half-life on rp-process reaction flow is explored. Implications on theoretical treatments of nuclear deformation in Mo84 are also discussed.

  19. Precision measurement of the half-life and the decay branches of Ga-62

    Canchel, G; Blank, B; Chartier, N; Delalee, F; Dendooven, P; Dossat, C; Giovinazzo, J; Huikari, J; Lalleman, AS; Jimenez, MJL; Madec, [No Value; Pedroza, JL; Penttila, H


    In an experiment performed at the Accelerator Laboratory of the University of Jyvaskyla, the beta-decay half-life of Ga-62 has been studied with high precision rising the IGISOL technique. A half-life of T-1/2 = 116.09(17) ms was nieasured. Using beta-gamma coincidences, the gamma intensity of the 9

  20. Static and dynamic half-life and lifetime molecular turnover of enzymes.

    Miyawaki, Osato; Kanazawa, Tsukasa; Maruyama, Chika; Dozen, Michiko


    The static half-life of an enzyme is the half-life of a free enzyme not working without substrate and the dynamic half-life is that of an active enzyme working with plenty amount of substrate. These two half-lives were measured and compared for glucoamylase (GA) and β-galactosidase (BG). The dynamic half-life was much longer than the static half-life by one to three orders of magnitude for both enzymes. For BG, the half-life of the enzyme physically entrapped in a membrane reactor was also measured. In this case also, the half-life of BG in the membrane reactor was much longer than the free enzyme without substrate. These results suggest the large difference in stabilities between the free enzyme and the enzyme-substrate complex. This may be related to the natural enzyme metabolism. According to the difference in half-life, the lifetime molecular turnover (LMT), which is the number of product molecules produced by a single molecule of enzyme until it loses its activity completely, was much higher by one to four orders of magnitude for the active enzyme than the free enzyme. The concept of LMT, proposed here, will be important in bioreactor operations with or without immobilization. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Precision measurement of the half-life of $^{109}$In in large and small lattice environments

    We propose to undertake high precision measurements of the half-life of $^{109}$In in large and small lattice environments to study the effect of compression on the electron capture nuclear decay rate. Such studies are of general interest having implications in many areas ranging from astrophysics to geophysics. At present, very little data is available on the change of electron capture decay rate under compression and the available data seems to indicate that the observed increase of the electron capture decay rate under compression is much greater than the predictions of the best available density functional calculations as obtained from TB-LMTO or WIEN2K codes. The proposed experiment should generate more data thus clarifying the experimental situation.

  2. Q value and half-life of double-electron capture in Os-184

    Smorra, C; Beyer, T; Blaum, K; Block, M; Düllmann, Ch E; Eberhardt, K; Eibach, M; Eliseev, S; Langanke, K; Martinez-Pinedo, G; Nagy, Sz; Nörtershäuser, W; Renisch, D; Shabaev, V M; Tupitsyn, I I; Zubova, N A


    Os-184 has been excluded as a promising candidate for the search of neutrinoless double-electron capture. High-precision mass measurements with the Penning-trap mass spectrometer TRIGA-TRAP resulted in a marginal resonant enhancement with = -8.89(58) keV excess energy to the 1322.152(22) keV 0+ excited state in W-184. State-of-the-art energy density functional calculations are applied for the evaluation of the nuclear matrix elements to the excited states predicting a strong suppression due to the large deformation of mother and daughter states. The half-life of the transition in Os-184 exceeds T_{1/2} > 1.3 10^{29} years for an effective neutrino mass of 1 eV.

  3. PASylation of Murine Leptin Leads to Extended Plasma Half-Life and Enhanced in Vivo Efficacy.

    Morath, Volker; Bolze, Florian; Schlapschy, Martin; Schneider, Sarah; Sedlmayer, Ferdinand; Seyfarth, Katrin; Klingenspor, Martin; Skerra, Arne


    Leptin plays a central role in the control of energy homeostasis and appetite and, thus, has attracted attention for therapeutic approaches in spite of its limited pharmacological activity owing to the very short circulation in the body. To improve drug delivery and prolong plasma half-life, we have fused murine leptin with Pro/Ala/Ser (PAS) polypeptides of up to 600 residues, which adopt random coil conformation with expanded hydrodynamic volume in solution and, consequently, retard kidney filtration in a similar manner as polyethylene glycol (PEG). Relative to unmodified leptin, size exclusion chromatography and dynamic light scattering revealed an approximately 21-fold increase in apparent size and a much larger molecular diameter of around 18 nm for PAS(600)-leptin. High receptor-binding activity for all PASylated leptin versions was confirmed in BIAcore measurements and cell-based dual-luciferase assays. Pharmacokinetic studies in mice revealed a much extended plasma half-life after ip injection, from 26 min for the unmodified leptin to 19.6 h for the PAS(600) fusion. In vivo activity was investigated after single ip injection of equimolar doses of each leptin version. Strongly increased and prolonged hypothalamic STAT3 phosphorylation was detected for PAS(600)-leptin. Also, a reduction in daily food intake by up to 60% as well as loss in body weight of >10% lasting for >5 days was observed, whereas unmodified leptin was merely effective for 1 day. Notably, application of a PASylated superactive mouse leptin antagonist (SMLA) led to the opposite effects. Thus, PASylated leptin not only provides a promising reagent to study its physiological role in vivo but also may offer a superior drug candidate for clinical therapy.

  4. Stable isotope turnover and half-life in animal tissues: a literature synthesis.

    Vander Zanden, M Jake; Clayton, Murray K; Moody, Eric K; Solomon, Christopher T; Weidel, Brian C


    Stable isotopes of carbon, nitrogen, and sulfur are used as ecological tracers for a variety of applications, such as studies of animal migrations, energy sources, and food web pathways. Yet uncertainty relating to the time period integrated by isotopic measurement of animal tissues can confound the interpretation of isotopic data. There have been a large number of experimental isotopic diet shift studies aimed at quantifying animal tissue isotopic turnover rate λ (%·day(-1), often expressed as isotopic half-life, ln(2)/λ, days). Yet no studies have evaluated or summarized the many individual half-life estimates in an effort to both seek broad-scale patterns and characterize the degree of variability. Here, we collect previously published half-life estimates, examine how half-life is related to body size, and test for tissue- and taxa-varying allometric relationships. Half-life generally increases with animal body mass, and is longer in muscle and blood compared to plasma and internal organs. Half-life was longest in ecotherms, followed by mammals, and finally birds. For ectotherms, different taxa-tissue combinations had similar allometric slopes that generally matched predictions of metabolic theory. Half-life for ectotherms can be approximated as: ln (half-life) = 0.22*ln (body mass) + group-specific intercept; n = 261, plife can be approximated using simple allometric relationships for some taxa and tissue types, there is also a high degree of unexplained variation in our models. Our study highlights several strong and general patterns, though accurate prediction of isotopic half-life from readily available variables such as animal body mass remains elusive.

  5. Update of NIST half-life results corrected for ionization chamber source-holder instability.

    Unterweger, M P; Fitzgerald, R


    As reported at the ICRM 2011, it was discovered that the source holder used for calibrations in the NIST 4πγ ionization chamber (IC) was not stable. This has affected a large number of half-life measurement results previously reported and used in compilations of nuclear data. Corrections have been made on all of the half-life data based on the assumption that the changes to the ionization chamber response were gradual. The corrections are energy dependent and therefore radionuclide specific. This presentation will review our results and present the recommended changes in half-life values and/or uncertainties.

  6. Determination of (137)Cs half-life with an ionization chamber.

    Juget, Frédéric; Nedjadi, Youcef; Buchillier, Thierry; Bochud, François; Bailat, Claude


    The half-life of (137)Cs was measured with an ionization chamber by following the decay of 5 sources over a 30 years period between 1983 and 2013. The ratio between the ionization chamber current for the cesium sources and (226)Ra source was used for the half-life calculation. The value found for the (137)Cs half-life is 10,955.2±10.7 days, where the uncertainty evaluation combines type A and B for one standard deviation.

  7. Half-life of Si-32 from tandem-accelerator mass spectrometry

    Elmore, D.; Anantaraman, N.; Fulbright, H. W.; Gove, H. E.; Nishiizumi, K.; Murrell, M. T.; Honda, M.; Hans, H. S.


    A newly developed mass-spectrometry technique employing a tandem Van de Graaff accelerator together with a special beam-transport system and heavy-ion detector has been used to determine the half-life of Si-32. The result obtained, 108 plus or minus 18 yr, disagrees with the accepted value of 330 plus or minus 40 yr. The implications of the new half-life of Si-32, which is used for dating studies, are discussed.

  8. Dependence of the half-life of 221Fr on the implantation environment

    Olaizola, B.; Fraile, L.M.; Riisager, Karsten


    The possible dependence of the half-life of 221Fr on the solid-state environment has been investigated by the simultaneous measurement of implanted 221Fr ions in an insulator (Si) and a metallic substrate (Au) at the ISOLDE facility at CERN. Our results indicate that, if existing, the difference...... in half-life does not follow a systematic trend and it is well below 1%...

  9. Variation in absorption and half-life of hydrocortisone influence plasma cortisol concentrations.

    Hindmarsh, Peter C; Charmandari, Evangelia


    Hydrocortisone therapy should be individualized in congenital adrenal hyperplasia (CAH) patients to avoid over and under replacement. We have assessed how differences in absorption and half-life of cortisol influence glucocorticoid exposure. Forty-eight patients (21 M) aged between 6·1 and 20·3 years with CAH due to CYP21A2 deficiency were studied. Each patient underwent a 24-h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m(2) body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (Cmax ), time of maximum plasma concentration (tmax ), time to attaining plasma cortisol concentration cortisol. Mean half-life was 76·5 ± 5·2 (range 40-225·3) min, Cmax 780·7 ± 61·6 nmol/l and tmax 66·7 (range 20-118) min. Time taken to a plasma cortisol concentration less than 100 nmol/l was 289 (range 140-540) min. Those with a fast half-life and slow tmax took longest to reach a plasma cortisol concentration less than 100 nmol/l (380 ± 34·6 min), compared to those with a slow half-life and fast tmax (298 ± 34·8 min) and those with a fast half-life and fast tmax (249·5 ± 14·4 min) (One-way anovaF = 4·52; P = 0·009). Both rate of absorption and half-life of cortisol in the circulation play important roles in determining overall exposure to oral glucocorticoid. Dose regimens need to incorporate estimates of these parameters into determining the optimum dosing schedule for individuals. © 2014 John Wiley & Sons Ltd.

  10. Using gamma distribution to determine half-life of rotenone, applied in freshwater

    Rohan, Maheswaran, E-mail: [Department of Biostatistics and Epidemiology, Auckland University of Technology, Auckland (New Zealand); Fairweather, Alastair; Grainger, Natasha [Science and Capability, Department of Conservation, Hamilton (New Zealand)


    Following the use of rotenone to eradicate invasive pest fish, a dynamic first-order kinetic model is usually used to determine the half-life and rate at which rotenone dissipated from the treated waterbody. In this study, we investigate the use of a stochastic gamma model for determining the half-life and rate at which rotenone dissipates from waterbodies. The first-order kinetic and gamma models produced similar values for the half-life (4.45 days and 5.33 days respectively) and days to complete dissipation (51.2 days and 52.48 days respectively). However, the gamma model fitted the data better and was more flexible than the first-order kinetic model, allowing us to use covariates and to predict a possible range for the half-life of rotenone. These benefits are particularly important when examining the influence that different environmental factors have on rotenone dissipation and when trying to predict the rate at which rotenone will dissipate during future operations. We therefore recommend that in future the gamma distribution model is used when calculating the half-life of rotenone in preference to the dynamic first-order kinetics model. - Highlights: • We investigated the use of the gamma model to calculate the half-life of rotenone. • Physical and environmental variables can be incorporated into the model. • A method for calculating the range around a mean half-life is presented. • The model is more flexible than the traditionally used first-order kinetic model.

  11. Designing of peptides with desired half-life in intestine-like environment

    Sharma, Arun


    Background: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life.Results: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides.Conclusion: In summary, this study describes a web server \\'HLP\\' that has been developed for assisting scientific

  12. Re-measurement of the half-life of sup 7 sup 9 Se

    Jiang Song Sheng; Diao Li Jun; Li Chun Shen; GouJingRu; Wu Shao Yon


    A new attempt has been made for the re-measurement of the half-life of sup 7 sup 9 Se. We made two major improvements over our earlier sup 7 sup 9 Se half-life determination (Nucl. Instr. and Meth. B 123 (1997) 403). Firstly, the half-life of sup 7 sup 9 Se was measured relative to the precisely known half-life of sup 7 sup 5 Se, rather than an absolute measurement of sup 7 sup 9 Se/Se. Secondly, the Projectile X-ray Detection technique was used for the separation of sup 7 sup 9 Se from its isobar, sup 7 sup 9 Br, rather than measuring sup 8 sup 1 Br for the deduction of sup 7 sup 9 Br interference, and this technique was also used for separation of sup 7 sup 5 Se and its isobar, sup 7 sup 5 As. A detailed description of the sample preparations, experimental setup and measurements are given. The re-measured half-life of sup 7 sup 9 Se was (2.95+-0.38)x10 sup 5 a, about a factor of 3 lower than the previous value, 1.1x10 sup 6 a. The problems in the previous measurement are discussed.

  13. Measurement of the half-life of sup 7 sup 9 Se with PX-AMS

    He Ming; Jiang Shan; Diao Li Jun; Wu Shao Yon; Li Chun Shen


    The half-life of sup 7 sup 9 Se has been re-measured with projectile X-rays detection (PXD) in accelerator mass spectrometry after a new PXD system had been set up in China Institute of Atomic Energy (CIAE). The PXD technique has been used for separation of sup 7 sup 9 Se from its isobar, sup 7 sup 9 Br. The detection efficiency of sup 7 sup 9 Se K subalpha X-rays is obtained from that of sup 8 sup 0 Se after energy correction. The atom number of sup 7 sup 9 Se in each sample is deduced from the measured ratios of sup 7 sup 9 Se/Se. From the measured decay rates of each sample, the half-life is deduced to be (2.80+-0.36)x10 sup 5 a. In order to check the reliability of the result of sup 7 sup 9 Se half-life, the sup 7 sup 5 Se half-life is also measured with PX-AMS method. The measured half-life of sup 7 sup 5 Se is in good agreement with well-known literature value.

  14. Kinetic modeling and half life study on bioremediation of crude oil dispersed by Corexit 9500

    Zahed, Mohammad Ali [School of Civil Engineering, Universiti Sains Malaysia, Engineering Campus, 14300 Nibong Tebal, Penang (Malaysia); Aziz, Hamidi Abdul, E-mail: [School of Civil Engineering, Universiti Sains Malaysia, Engineering Campus, 14300 Nibong Tebal, Penang (Malaysia); Isa, Mohamed Hasnain [Civil Engineering Department, Universiti Teknologi PETRONAS, 31750 Tronoh, Perak (Malaysia); Mohajeri, Leila; Mohajeri, Soraya [School of Civil Engineering, Universiti Sains Malaysia, Engineering Campus, 14300 Nibong Tebal, Penang (Malaysia); Kutty, Shamsul Rahman Mohamed [Civil Engineering Department, Universiti Teknologi PETRONAS, 31750 Tronoh, Perak (Malaysia)


    Hydrocarbon pollution in marine ecosystems occurs mainly by accidental oil spills, deliberate discharge of ballast waters from oil tankers and bilge waste discharges; causing site pollution and serious adverse effects on aquatic environments as well as human health. A large number of petroleum hydrocarbons are biodegradable, thus bioremediation has become an important method for the restoration of oil polluted areas. In this research, a series of natural attenuation, crude oil (CO) and dispersed crude oil (DCO) bioremediation experiments of artificially crude oil contaminated seawater was carried out. Bacterial consortiums were identified as Acinetobacter, Alcaligenes, Bacillus, Pseudomonas and Vibrio. First order kinetics described the biodegradation of crude oil. Under abiotic conditions, oil removal was 19.9% while a maximum of 31.8% total petroleum hydrocarbons (TPH) removal was obtained in natural attenuation experiment. All DCO bioreactors demonstrated higher and faster removal than CO bioreactors. Half life times were 28, 32, 38 and 58 days for DCO and 31, 40, 50 and 75 days for CO with oil concentrations of 100, 500, 1000 and 2000 mg/L, respectively. The effectiveness of Corexit 9500 dispersant was monitored in the 45 day study; the results indicated that it improved the crude oil biodegradation rate.

  15. Measurement of the two neutrino double beta decay half-life of Zr-96 and search for associated neutrinoless processes with the NEMO-3 detector

    Argyriades, J; Augier, C; Baker, J; Barabash, A S; Bongrand, M; Broudin-Bay, G; Brudanin, V B; Caffrey, A J; Chapon, A; Chauveau, E; Daraktchieva, Z; Durand, D; Egorov, V G; Fatemi-Ghomi, N; Flack, R; Freshville, A; Guillon, B; Hubert, Ph; Jullian, S; Kauer, M; King, S; Kochetov, O I; Konovalov, S I; Kovalenko, V E; Lalanne, D; Lang, K; Lemiere, Y; Lutter, G; Mamedov, F; Marquet, Ch; Martín-Albo, J; Mauger, F; Nachab, A; Nasteva, I; Nemchenok, I B; Nova, F; Novella, P; Ohsumi, H; Pahlka, R B; Perrot, F; Piquemal, F; Reyss, J L; Ricol, J S; Saakyan, R; Sarazin, X; Simard, L; Shitov, Yu A; Smolnikov, A A; Snow, S; Söldner-Rembold, S; Stekl, I; Sutton, C S; Szklarz, G; Thomas, J; Timkin, V V; Tretyak, V I; Tretyak, Vl I; Umatov, V I; Vàla, L; Vanyushin, I A; Vasiliev, V A; Vorobel, V; Vylov, Ts


    Using 1221 days of data from the NEMO-3 detector, the measurement of Zr-96 2vbb decay half-life is [2.35 +/- 0.14(stat) +/- 0.19(syst)] x 10^19 yr. Different characteristics of the final state electrons have been studied, such as the energy sum, individual electron energy, and angular distribution. The 2v nuclear matrix element is extracted using the measured 2vbb half-life and is 0.049 +/- 0.003. A 90% CL limit is set on the 0vbb decay half-life of > 9.2 x 10^21 yr corresponding to a limit on the effective Majorana neutrino mass < 7.2 - 19.5 eV. Limits on other mechanisms of 0vbb decay have also been set.

  16. Determination of the half-life of 213Fr with high precision

    Fisichella, M.; Musumarra, A.; Farinon, F.; Nociforo, C.; Del Zoppo, A.; Figuera, P.; La Cognata, M.; Pellegriti, M. G.; Scuderi, V.; Torresi, D.; Strano, E.


    High-precision measurement of half-life and Qα value of neutral and highly charged α emitters is a major subject of investigation currently. In this framework, we recently pushed half-life measurements of neutral emitters to a precision of a few per mil. This result was achieved by using different techniques and apparatuses at Istituto Nazionale di Fisica Nucleare Laboratori Nazionali del Sud (INFN-LNS) and GSI Darmstadt. Here we report on 213Fr half-life determination [T1/2(213Fr) = 34.14±0.06 s] at INFN-LNS, detailing the measurement protocol used. Direct comparison with the accepted value in the literature shows a discrepancy of more than three sigma. We propose this new value as a reference, discussing previous experiments.

  17. β-decay half-life of V50 calculated by the shell model

    Haaranen, M.; Srivastava, P. C.; Suhonen, J.; Zuber, K.


    In this work we survey the detectability of the β- channel of 2350V leading to the first excited 2+ state in 2450Cr. The electron-capture (EC) half-life corresponding to the transition of 2350V to the first excited 2+ state in 2250Ti had been measured earlier. Both of the mentioned transitions are 4th-forbidden non-unique. We have performed calculations of all the involved wave functions by using the nuclear shell model with the GXPF1A interaction in the full f-p shell. The computed half-life of the EC branch is in good agreement with the measured one. The predicted half-life for the β- branch is in the range ≈2×1019 yr whereas the present experimental lower limit is 1.5×1018 yr. We discuss also the experimental lay-out needed to detect the β--branch decay.

  18. Three-Laboratory Measurement of the {sup 44}Ti Half-Life

    Ahmad, I.; Fischer, S.M.; Kutschera, W.; Paul, M. [Physics Division, Argonne National Laboratory, Argonne, Illinois 60439 (United States); Bonino, G.; Bonino, G.; Castagnoli, G.C.; Castagnoli, G.C. [Dipartimento di Fisica Generale dell`Universita, Via P. Giuria 1, I-10125 Torino (Italy); Kutschera, W. [Institut fuer Radiumforschung und Kernphysik der Universitaet Wien, Boltzmanngasse 3, A-1090 Vienna (Austria); Paul, M. [Racah Institute of Physics, Hebrew University, Jerusalem, Israel 91904] [University of Chicago, Chicago, Illinois 60637 (United States)


    We report on a measurement of the {sup 44}Ti half-life aimed at lowering existing systematic uncertainties in this value, which is important to astrophysics. The half-life was measured by following the decay of {sup 44}Ti relative to {sup 60}Co for about 5yr and the measurements were performed independently in three laboratories{emdash}Argonne, Jerusalem, and Torino. We suggest to combine our result, 59.0{plus_minus}0.6yr, with the one from the accompanying Letter by G{umlt o}rres {ital et al.,} 60.3{plus_minus}1.3yr, to obtain a current {open_quotes}best value{close_quotes} for the half-life of {sup 44}Ti of 59.2{plus_minus}0.6 yr (1{sigma} error). {copyright} {ital 1998} {ital The American Physical Society}

  19. Movement Complexity and Neuromechanical Factors Affect the Entropic Half-Life of Myoelectric Signals

    Emma F. Hodson-Tole


    Full Text Available Appropriate neuromuscular functioning is essential for survival and features underpinning motor control are present in myoelectric signals recorded from skeletal muscles. One approach to quantify control processes related to function is to assess signal variability using measures such as Sample Entropy. Here we developed a theoretical framework to simulate the effect of variability in burst duration, activation duty cycle, and intensity on the Entropic Half-Life (EnHL in myoelectric signals. EnHLs were predicted to be <40 ms, and to vary with fluctuations in myoelectric signal amplitude and activation duty cycle. Comparison with myoelectic data from rats walking and running at a range of speeds and inclines confirmed the range of EnHLs, however, the direction of EnHL change in response to altered locomotor demand was not correctly predicted. The discrepancy reflected different associations between the ratio of the standard deviation and mean signal intensity (Ist:It¯ and duty factor in simulated and physiological data, likely reflecting additional information in the signals from the physiological data (e.g., quiescent phase content; variation in action potential shapes. EnHL could have significant value as a novel marker of neuromuscular responses to alterations in perceived locomotor task complexity and intensity.

  20. Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life.

    Stabile, F; Barnett, C R; De Risio, L


    Estimated prevalence of canine idiopathic epilepsy is 0.6 per cent in the first-opinion canine population in the UK. Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60-93 per cent of idiopathic epileptic dogs (IEDs). The objective of this study was to evaluate safety and efficacy of the administration of phenobarbital orally every eight hours in IEDs with phenobarbital elimination half-life less than 20 hours. Medical records of 10 IEDs in which steady state trough serum phenobarbital levels were within the reference range and phenobarbital elimination half-life had become less than 20 hours following prolonged administration every 12 hours were reviewed. Side effects and seizure frequency when phenobarbital was administered every 12 hours or 8 hours were compared. In all dogs the side effects of the antiepileptic medication treatment improved. When phenobarbital was administered every eight hours, 9/10 dogs experienced improvement in seizure frequency and 8/10 dogs maintained seizure freedom for a period three times longer than the longest interictal interval period previously recorded. Reduction in the severity and number of clusters of seizures was recorded in one of the remaining two dogs. The administration of phenobarbital orally every eight hours in IEDs with decreased phenobarbital elimination half-life appears safe and can improve seizure management. The results of this study were presented in abstract form (poster) for the 28th symposium of the European Society of Veterinary Neurology - European College of Veterinary Neurology (ESVN), September 18-19, 2015, Amsterdam, Netherlands. British Veterinary Association.

  1. Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

    Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt


    BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

  2. Study on Radiochemical Separation and Measurement of Half-life of ~(88)Kr


    88Kr is one of the important gaseous fission products for determining the burn up of nuclear fuel with a short half-life, high fission yield and high branch ratio of γ-ray. Due to the more uncertainty of evaluated data and rare experimented data,

  3. Innovative methodology for intercomparison of radionuclide calibrators using short half-life in situ prepared radioactive sources

    Oliveira, P. A. [Centro de Investigação do Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto, Portugal and Departamento de Física e Astronomia, Faculdade de Ciências da Universidade do Porto (Portugal); Santos, J. A. M., E-mail: [Centro de Investigação do Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto (Portugal); Serviço de Física Médica do Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto (Portugal); Serviço de Medicina Nuclear do Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto (Portugal); Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto (Portugal)


    Purpose: An original radionuclide calibrator method for activity determination is presented. The method could be used for intercomparison surveys for short half-life radioactive sources used in Nuclear Medicine, such as{sup 99m}Tc or most positron emission tomography radiopharmaceuticals. Methods: By evaluation of the resulting net optical density (netOD) using a standardized scanning method of irradiated Gafchromic XRQA2 film, a comparison of the netOD measurement with a previously determined calibration curve can be made and the difference between the tested radionuclide calibrator and a radionuclide calibrator used as reference device can be calculated. To estimate the total expected measurement uncertainties, a careful analysis of the methodology, for the case of{sup 99m}Tc, was performed: reproducibility determination, scanning conditions, and possible fadeout effects. Since every factor of the activity measurement procedure can influence the final result, the method also evaluates correct syringe positioning inside the radionuclide calibrator. Results: As an alternative to using a calibrated source sent to the surveyed site, which requires a relatively long half-life of the nuclide, or sending a portable calibrated radionuclide calibrator, the proposed method uses a source preparedin situ. An indirect activity determination is achieved by the irradiation of a radiochromic film using {sup 99m}Tc under strictly controlled conditions, and cumulated activity calculation from the initial activity and total irradiation time. The irradiated Gafchromic film and the irradiator, without the source, can then be sent to a National Metrology Institute for evaluation of the results. Conclusions: The methodology described in this paper showed to have a good potential for accurate (3%) radionuclide calibrators intercomparison studies for{sup 99m}Tc between Nuclear Medicine centers without source transfer and can easily be adapted to other short half-life radionuclides.

  4. 89Rb半衰期测量%Half-life Measurement of 89 Rb

    郭晓清; 袁大庆; 徐利军; 陈克胜; 吴永乐; 郑艳明; 姚顺和


    89 Rb is an important fission product used for monitoring possible release of fission products from fuel element .The half-life is one of important nuclear parameters . The half-life of 89 Rb was determined using reference source method with two sets of HPGe detectors by place-relay way .In reference source method ,the ratio of net full-energy peak areas from the measure nuclide and the reference source was used to avoid the count correction caused by dead time and pileup .For the very short half-life of 89 Rb , the half-life iterative method was used in data analysis and the translation method was used in data unification .Finally ,the measured half-life of 89 Rb is (14.41 ± 0.04) min .%89 Rb是重要的裂变产物核素,半衰期是其一项非常重要的核参数。本文采用参考源法,运用双HPGe探头距离接续测定了89 Rb的半衰期。参考源法利用待测源和参考源的γ射线全能峰之比消除了测量过程中死时间和脉冲堆积带来的计数修正影响。由于89 Rb半衰期较短,数据分析运用了半衰期迭代法,并用平移法归一探头测量数据,最终实验测得89 Rb半衰期为(14.41±0.04) min。

  5. Determination of the 10Be half-life by multicollector ICP-MS and liquid scintillation counting

    Chmeleff, Jérôme; von Blanckenburg, Friedhelm; Kossert, Karsten; Jakob, Dieter


    A new method was designed and used for determining the half-life of the isotope 10Be. The method is based on (1) accurate 10Be/ 9Be measurements of 9Be-spiked solutions of a 10Be-rich master solution using multicollector ICP mass spectrometry (MC-ICP-MS) and (2) liquid scintillation counting (LSC) using the CIEMAT/NIST method for determining the activity concentrations of the solutions whose 10Be concentrations were determined by mass spectrometry. Important requirements for the success of this approach (a) was the previous coating of glass ampoules filled for counting experiments with 9Be, thereby reducing the risk of the adsorptive loss of 10Be; (b) the removal of Boron from solutions to be measured by MC-ICP-MS by cation chromatography without the introduction of mass fractionation and (c) the accurate determination of the mass bias of 10Be/ 9Be measurements by ICP-MS which are always affected by the space-charge effect. The mass bias factor was determined to be 1.1862 ± 0.071 for 10Be/ 9Be from careful fitting and error propagation of ratios of measured Li, B, Si, Cr, Fe, Cu, Sr, Nd, Hf, Tl and U standard solutions of known composition under the same measurement conditions. Employing this factor, an absolute 10Be/ 9Be ratio of 1.464 ± 0.014 was determined for a first dilution of the 10Be-rich master solution. This solution is now available as an absolute Be ratio standard in AMS measurements. Finally, a half-life of (1.386 ± 0.016) My (standard uncertainty) was calculated. This value is much more precise than previous estimates and was derived from a fully independent set of experiments. In a parallel, fully independent study using the same master solution, Korschinek et al. [35] have determined a half-life of (1.388 ± 0.018) My. The combined half-life and uncertainty amounts to (1.387 ± 0.012) My. We suggest the use of this value in nuclear studies and in studies that make use of cosmogenic 10Be in environmental and geologic samples.

  6. Half-life and rational drug use of paclitaxel%紫杉醇的半衰期与合理用药



    In this article,the author mainly discusses the relationship of paclitaxel drug metabolism in human body and its half-life to promote its rational drug use.Refer to the relevant medical literature at home and abroad in recent years,we have induction and summary.The relationship of paclitaxel half-life and pesticide effect is analyzed.The paclitaxel half-life can determine the metabolism degree of the drug in the body,so drug half-life plays a critical role in the process of rational drug use.%本文主要对紫杉醇药物在人体内的代谢与其半衰期的关系进行探讨,以促进其合理用药。笔者参阅近几年来国内外的相关医学文献,进行归纳、总结,分析紫杉醇半衰期与药效之间的关系。根据紫杉醇的半衰期可以判定药物在人体内的代谢程度,因此药物半衰期在合理用药的过程中发挥着至关重要的作用。

  7. A half-life the divided life of Bruno Pontecorvo, physicist or spy

    Close, Frank


    Bruno Pontecorvo dedicated his career to hunting for the Higgs boson of his day: the neutrino, a nearly massless particle considered essential to the process of nuclear fission. His work on the Manhattan project under Enrico Fermi confirmed his reputation as a brilliant physicist and helped usher in the nuclear age. He should have won a Nobel Prize, but late in the summer of 1950 he vanished. At the height of the Cold War, Pontecorvo had disappeared behind the Iron Curtain. In Half-Life, physicist and historian Frank Close offers a heretofore untold history of Pontecorvo’s life, based on unprecedented access to his friends, family, and colleagues. With all the elements of a Cold War thriller—classified atomic research, an infamous double agent, a kidnapping by Soviet operatives—Half-Life is a history of particle physics at perhaps its most powerful: when it created the bomb.

  8. Half-life and inner penetrability in the cold fission of {sup 248}Cm

    Kunhikrishnan, P.V. [Sree Narayana College, Department of Physics, Kannur (India); Santhosh, K.P. [Kannur University, School of Pure and Applied Physics, Payyanur (India); Joseph, Antony [University of Calicut, Department of Physics, Malappuram, Kerala (India)


    Using the Coulomb and proximity potential model (CPPM) with the nuclear surface tension improved by Reisdorf, the various fragmentations in the cold fission of {sup 248}Cm are studied as a cluster decay process within a fission model. The computed half-life values are compared with the values reported by Sandulescu et al. using the double-folding M3Y nuclear-nuclear potential model and are in agreement with CPPM values. The diffuseness width used in the proximity potential is found to be sensitive to the half-life. The inner penetrability is computed based on the formalism of Poenaru et al. (J. Phys. G: Nucl. Part. Phys. 17, 443 (1991)) and found that in the cold fission the contribution of the inner part (overlap region) of the barrier is significant compared to cluster decays. The variation of the inner penetrability with fragment mass is studied which emphasizes the fact that cold fission is an extension of cluster decay. (orig.)

  9. Precision half-life measurement of the 4-fold forbidden β decay of V50

    Dombrowski, H.; Neumaier, S.; Zuber, K.


    A sensitive search of the 4-fold forbidden nonunique decay of V50 has been performed. A total mass measuring time product of 186 kg d has been accumulated. A reliable half-life value with the highest precision so far of (2.29±0.25)×1017 years of the electron capture decay of V50 into the first excited state of Ti50 could be obtained. A photon emission line following the β decay into the first excited state of Cr50 could not be observed, resulting in a lower limit on the half-life of the β-decay branch of 1.7×1018 years. This is not in good agreement with a claimed observation of this decay branch published in 1989.

  10. Unified description of the proton, alpha, cluster decays and spontaneously fissions half- life

    Mavrodiev, Strachimir Cht


    Some time ago the possibility of classical (without Gamow tunneling) universal description of radioactive nuclei decay was demonstrated. Such possibility is basis on the classical interpretation of Bohmian Psi-field reality in Bohmian-Chetaev mechanics and the hypothesis for the presence of dissipative forces, generated from the Gryzinski translational precession of the charged particles spin, in Langevin- Kramers diffusion mechanism. In this paper is present an unified model of proton, alpha decay, cluster radioactivity and spontaneous fission half-life as explicit function which depends on the total decay energy and kinetic energy, the number of protons and neutrons of daughter product, the number of protons and neutrons of mother nuclei and from a set) unknown digital parameters. The Half- lifes of the 573 nuclei taken from NuDat database together with the recent experimental data from Oganessian provide a basis for discovering the explicit form of the Kramers solution of Langevin type equation in a framew...

  11. Theoretical half-life for beta decay of {sup 96}Zr

    Heiskanen, H; Mustonen, M T; Suhonen, J [Department of Physics, University of Jyvaeskylae, PO Box 35, FIN-40351, Jyvaeskylae (Finland)


    Highly forbidden {beta}{sup -} decay of the 0{sup +} ground state of {sup 96}Zr is studied. Partial half-lives to the lowest 6{sup +}, 5{sup +} and 4{sup +} states of {sup 96}Nb have been computed using the proton-neutron quasiparticle random-phase approximation (pnQRPA) with realistic two-body interactions in a large single-particle space. We find that the decay is dominated by the unique fourth-forbidden transition to the 5{sup +} state with the half-life 2.4 x 10{sup 20} y. This half-life is an order of magnitude longer than the one measured for the double beta decay of {sup 96}Zr.

  12. Precise Half-Life Measurement of the Superallowed beta emitter 10C

    Iacob, V E; Golovko, V; Goodwin, J; Nica, N; Park, H I; Trache, L; Tribble, R E


    The half-life of 10C has been measured to be 19.310(4)s, a result with 0.02% precision, which is a factor of three improvement over the best previous result. Since 10C is the lightest superallowed 0+ --> 0+ beta emitter, its ft value has the greatest weight in setting an upper limit on the possible presence of scalar currents.

  13. Discussions about whether radioactive half life can be changed by mechanic motion


    In this essay, some discussions and comments about the paper entitled "Can the decay rate of 32P be changed by mechanic motion?" (Ding et al., Science in China Series B:Chemistry (Chinese version), 2008, 38(11):1035-1037) are given. It was strongly suggested that its experimental methods, data calculations and conclusion should be reconsidered. After the data were recalculated, the new results supported that the chiral mechanic motion could induce the changes of radioactive half life.

  14. The half-life and exposure of cefuroxime varied in newborn infants after a Caesarean section

    Zachariassen, G.; Hyldig, N.; Joergensen, J.S.


    in normal adults and seemed to clear within 24 hours. The median area under the concentration–time curve was 65.0 hour μg/mL (range 31.7–162.4). Conclusion: We found that the cefuroxime half-life after a Caesarean section varied among infants and was longer than in normal adults but cleared within 24 hours....... Exposure to cefuroxime in newborn infants may influence the gut microbiota and should be investigated further....

  15. Measurement of the Two-Neutrino Double Beta Decay Half-life of $^{130}$Te with the CUORE-0 Experiment

    Alduino, C; Artusa, D R; Avignone, F T; Azzolini, O; Banks, T I; Bari, G; Beeman, J W; Bellini, F; Bersani, A; Biassoni, M; Branca, A; Brofferio, C; Bucci, C; Camacho, A; Caminata, A; Canonica, L; Cao, X G; Capelli, S; Cappelli, L; Carbone, L; Cardani, L; Carniti, P; Casali, N; Cassina, L; Chiesa, D; Chott, N; Clemenza, M; Copello, S; Cosmelli, C; Cremonesi, O; Creswick, R J; Cushman, J S; D'Addabbo, A; Dafinei, I; Davis, C J; Dell'Oro, S; Deninno, M M; Di Domizio, S; Di Vacri, M L; Drobizhev, A; Fang, D Q; Faverzani, M; Fernandes, G; Ferri, E; Ferroni, F; Fiorini, E; Franceschi, M A; Freedman, S J; Fujikawa, B K; Giachero, A; Gironi, L; Giuliani, A; Gladstone, L; Gorla, P; Gotti, C; Gutierrez, T D; Haller, E E; Han, K; Hansen, E; Heeger, K M; Hennings-Yeomans, R; Hickerson, K P; Huang, H Z; Kadel, R; Keppel, G; Kolomensky, Yu G; Leder, A; Ligi, C; Lim, K E; Liu, X; Ma, Y G; Maino, M; Marini, L; Martinez, M; Maruyama, R H; Mei, Y; Moggi, N; Morganti, S; Mosteiro, P J; Napolitano, T; Nones, C; Norman, E B; Nucciotti, A; O'Donnell, T; Orio, F; Ouellet, J L; Pagliarone, C E; Pallavicini, M; Palmieri, V; Pattavina, L; Pavan, M; Pessina, G; Pettinacci, V; Piperno, G; Pira, C; Pirro, S; Pozzi, S; Previtali, E; Rosenfeld, C; Rusconi, C; Sangiorgio, S; Santone, D; Scielzo, N D; Singh, V; Sisti, M; Smith, A R; Taffarello, L; Tenconi, M; Terranova, F; Tomei, C; Trentalange, S; Vignati, M; Wagaarachchi, S L; Wang, B S; Wang, H W; Wilson, J; Winslow, L A; Wise, T; Woodcraft, A; Zanotti, L; Zhang, G Q; Zhu, B X; Zimmermann, S; Zucchelli, S


    We report on the measurement of the two-neutrino double beta decay half-life of $^{130}$Te with the CUORE-0 detector. From an exposure of 33.4 kg$\\cdot$y of TeO$_2$, the half-life is determined to be $T_{1/2}^{2\

  16. A novel method to determine the half-life of 32Si

    Schnabel, C.; Beer, J.; Clausen, H. B.


    A novel method using high-resolution 10Be concentrations to correct 32Si data from independently dated depth profiles is presented. It is demonstrated that by correcting 32Si deposition rates for temporal changes based on production rate fluctuations the derived half-life of 32Si agrees with half-life determinations based on physical measurements of artificial samples. Currently, the half-life of 32Si is not accurately known. Moreover, results from physical measurements of artificial samples yielded much shorter half-lives (100-172 yr) than results based on depth profiles. For depth profiles most results were between 250 and 300 yr (Clausen, 1973), with the exception of a relatively recent work on a varved lake sediment which resulted in 178 yr (Nijampurkar et al., 1998). Using high-resolution 10Be concentrations from the Dye3 ice-core each data point of the Northern hemisphere ice-core 32Si concentrations is corrected for temporal variations in deposition rate. This means that we assume that temporal variations in 32Si and 10Be deposition are identical instead of using the assumption of constant deposition rates that resulted in the long half-lives. In the case of the varved lake sediment, 32Si/Si ratios are corrected in the same way as 32Si concentrations for the ice cores. We present our results that half-lives of longer than 180 yr can be ruled out for 32Si and propose using 10Be and 32Si concentrations from the same samples of independently dated profiles as a new method to apply 32Si for dating purposes. Preliminary results have been presented at the QRA meeting in Glasgow 2006 {schnabel et al., 2006]. HB Clausen, Journal of Glaciology 12 (1973) 411. VN Nijampurkar et al., Earth and Planetary Science Letters 163 (1998) 191. C. Schnabel, J. Beer, HB Clausen, QRA annual discussion meeting Glasgow, 2006.

  17. An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life.

    Kimishima, Atsushi; Wenthur, Cody J; Zhou, Bin; Janda, Kim D


    Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design. Administration of these vaccines resulted in a significant blockade of opioid analgesic activity, along with an unprecedented increase in drug serum half-life and protection against lethal overdose.

  18. Determination of the half-life of sup 1 sup 0 sup 5 sup m Rh

    Kronenberg, A K; Weber, R; Esterlund, R A; Patzelt, P


    Following a fast chemical separation of Ru isotopes from a fission-product mixture, sup 1 sup 0 sup 5 sup m Rh was periodically extracted from its precursor (4.44-h sup 1 sup 0 sup 5 Ru) for measurements of its half-life. The new value for the T sub 1 sub / sub 2 of sup 1 sup 0 sup 5 sup m Rh of (43.0+-0.3) s resolves the long-standing conflict in the literature between the two earlier measured values of 45 and 30 s.

  19. The Half Life of the 53 keV Level in {sup 197}Pt

    Malmskog, S.G.


    The half life of the recently proposed 53 keV level in {sup 197}Pt has been measured to 18.5 {+-} 1.5 nsec using the delayed coincidence technique. This level, which is identified with the f{sub 5/2} single particle state, decays directly to the p{sub 1/2} ground state in {sup 197}Pt. The reduced E2 transition probability for this 53 keV transition has been deduced and compared with the results obtained for the corresponding transitions in other Pt, Hg, and Pb isotopes and with the theoretical predictions by Sorensen and by Wahlborn and Martinson.

  20. Calculation of the Aluminosilicate Half-Life Formation Time in the 2H Evaporator

    Fondeur, F.F.


    The 2H Evaporator contains large quantities of aluminosilicate solids deposited on internal fixtures. The proposed cleaning operations will dissolve the solids in nitric acid. Operations will then neutralize the waste prior to transfer to a waste tank. Combining recent calculations of heat transfer for the 2H Evaporator cleaning operations and laboratory experiments for dissolution of solid samples from the pot, the authors estimated the re-formation rate for aluminosilicates during cooling. The results indicate a half-life formation of 17 hours when evaporator solution cools from 60 degrees C and 9 hours when cooled from 90 degrees C.

  1. Precise Half-Life Measurement of the Superallowed Beta+ Emitter 46V

    Park, H I; Iacob, V E; Chen, L; Goodwin, J; Nica, N; Simmons, E; Trache, L; Tribble, R E


    The half-life of 46V has been measured to be 422.66(6) ms, which is a factor of two more precise than the best previous measurement. Our result is also consistent with the previous measurements, with no repeat of the disagreement recently encountered with Q_{EC} values measured for the same transition. The Ft value for the 46V superallowed transition, incorporating all world data, is determined to be 3074.1(26) s, a result consistent with the average Ft value of 3072.08(79) s established from the 13 best-known superallowed transitions.

  2. The evolution of drug-resistant malaria: the role of drug elimination half-life.

    Hastings, Ian M.; Watkins, William M; White, Nicholas J


    This paper seeks to define and quantify the influence of drug elimination half-life on the evolution of antimalarial drug resistance. There are assumed to be three general classes of susceptibility of the malaria parasite Plasmodium falciparum to a drug: Res0, the original, susceptible wildtype; Res1, a group of intermediate levels of susceptibility that are more tolerant of the drug but still cleared by treatment; and Res2, which is completely resistant to the drug. Res1 and Res2 resistance ...

  3. Measurement of the half-life of sup 1 sup 7 sup 6 Lu

    Nir-El, Y


    The half-life of sup 1 sup 7 sup 6 Lu was determined by measuring the disintegration rate of a solution of lutetium oxide, using a calibrated HPGe detector, and found to be (3.69+-0.02)x10 sup 1 sup 0 y. It is recommended that the current adopted value be calculated from the grouping of three published values since 1983, including our value, the weighted mean of which is (3.73+-0.01)x10 sup 1 sup 0 y.

  4. Gamma-spectrometric determination of the sup 8 sup 9 Sr isotope half-life

    Popov, Y S; Markushin, M N; Kupriyanov, V N; Timofeev, G A


    Using the method of semiconductor [Ge(Li)-detector] gamma-spectroscopy by the results of measurements of 913 keV ( sup 8 sup 9 Sr) gamma-line intensity for 6000 h, using as internal reference the 661.7 keV ( sup 1 sup 3 sup 7 Cs) gamma-line, the value of sup 8 sup 9 Sr isotope half-life has been calculated, which proved to be 1208+-9 h or 50.34+-0.37 days. Error is provided for confidential probability P = 0.95


    Samuel Enahoro Agarry


    Full Text Available In this study, comparative potential effects of commercial activated carbon (CAC and plantain peel-derived biochar (PPBC of different particle sizes and dosage to stimulate petroleum hydrocarbon biodegradation in soil were investigated. Microcosms containing soil were spiked with weathered Bonny light crude oil (WBLCO (10% w/w and amended with different particle sizes (0.02, 0.07 and 0.48 mm and dosage (20, 30 and 40 g of CAC and PPBC, respectively. The bioremediation experiments were carried out for a period of 28 days under laboratory conditions. The results showed that there was a positive relationship between the rate of petroleum hydrocarbons reduction and presence of the CAC and PPBC in crude oil contaminated soil microcosms. The WBLCO biodegradation data fitted well to the first-order kinetic model. The model revealed that WBLCO contaminated-soil microcosms amended with CAC and PPBC had higher biodegradation rate constants (k as well as lower half-life times (t1/2 than unamended soil (natural attenuation remediation system. The rate constants increased while half-life times decreased with decreased particle size and increased dosage of amendment agents. ANOVA statistical analysis revealed that WBLCO biodegradation in soil was significantly (p = 0.05 influenced by the addition of CAC and biochar amendment agents, respectively. However, Tukey’s post hoc test (at p = 0.05 showed that there was no significant difference in the bioremediation efficiency of CAC and PPBC. Thus, amendment of soils with biochar has the potential to be an inexpensive, efficient, environmentally friendly and relatively novel strategy to mitigate organic compound-contaminated soil.

  6. Study of the dependence of 198Au half-life on source geometry

    Lindstrom, R M; Buncher, J B; Greene, G L; Jenkins, J H; Krause, D E; Mattes, J J; Yue, A; 10.1016/j.nima.2010.06.270


    We report the results of an experiment to determine whether the half-life of \\Au{198} depends on the shape of the source. This study was motivated by recent suggestions that nuclear decay rates may be affected by solar activity, perhaps arising from solar neutrinos. If this were the case then the $\\beta$-decay rates, or half-lives, of a thin foil sample and a spherical sample of gold of the same mass and activity could be different. We find for \\Au{198}, $(T_{1/2})_{\\rm foil}/(T_{1/2})_{\\rm sphere} = 0.999 \\pm 0.002$, where $T_{1/2}$ is the mean half-life. The maximum neutrino flux at the sample in our experiments was several times greater than the flux of solar neutrinos at the surface of the Earth. We show that this increase in flux leads to a significant improvement in the limits that can be inferred on a possible solar contribution to nuclear decays.

  7. Changing Paradigm of Hemophilia Management: Extended Half-Life Factor Concentrates and Gene Therapy.

    Kumar, Riten; Dunn, Amy; Carcao, Manuel


    Management of hemophilia has evolved significantly in the last century-from recognition of the causative mechanism in the 1950s to commercially available clotting factor concentrates in the 1960s. Availability of lyophilized concentrates in the 1970s set the stage for home-based therapy, followed by introduction of virally attenuated plasma-derived, and then recombinant factor concentrates in the 1980s and 1990s, respectively. The subsequent years saw a paradigm shift in treatment goals from on-demand therapy to prophylactic factor replacement starting at an early age, to prevent hemarthrosis becoming the standard of care for patients with severe hemophilia. In the developed world, the increasing use of home-based prophylactic regimens has significantly improved the quality of life, and life expectancy of patients with severe hemophilia. Seminal developments in the past 5 years, including the commercial availability of extended half-life factor concentrates and the publication of successful results of gene therapy for patients with hemophilia B, promise to further revolutionize hemophilia care over the next few decades. In this review, we summarize the evolution of management for hemophilia, with a focus on extended half-life factor concentrates and gene therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Half-life determination for {sup 108}Ag and {sup 110}Ag

    Zahn, Guilherme S.; Genezini, Frederico A. [Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP, P.O. Box 11049, São Paulo, 05422-970 (Brazil)


    In this work, the half-life of the short-lived silver radionuclides {sup 108}Ag and {sup 110}Ag were measured by following the activity of samples after they were irradiated in the IEA-R1 reactor. The results were then fitted using a non-paralizable dead time correction to the regular exponential decay and the individual half-life values obtained were then analyzed using both the Normalized Residuals and the Rajeval techniques, in order to reach the most exact and precise final values. To check the validity of dead-time correction, a second correction method was also employed by means of counting a long-lived {sup 60}Co radioactive source together with the samples as a livetime chronometer. The final half-live values obtained using both dead-time correction methods were in good agreement, showing that the correction was properly assessed. The results obtained are partially compatible with the literature values, but with a lower uncertainty, and allow a discussion on the last ENSDF compilations' values.

  9. HALO--a Java framework for precise transcript half-life determination.

    Friedel, Caroline C; Kaufmann, Stefanie; Dölken, Lars; Zimmer, Ralf


    Recent improvements in experimental technologies now allow measurements of de novo transcription and/or RNA decay at whole transcriptome level and determination of precise transcript half-lives. Such transcript half-lives provide important insights into the regulation of biological processes and the relative contributions of RNA decay and de novo transcription to differential gene expression. In this article, we present HALO (Half-life Organizer), the first software for the precise determination of transcript half-lives from measurements of RNA de novo transcription or decay determined with microarrays or RNA-seq. In addition, methods for quality control, filtering and normalization are supplied. HALO provides a graphical user interface, command-line tools and a well-documented Java application programming interface (API). Thus, it can be used both by biologists to determine transcript half-lives fast and reliably with the provided user interfaces as well as software developers integrating transcript half-life analysis into other gene expression profiling pipelines. Source code, executables and documentation are available at

  10. High-Precision Half-life Measurements for the Superallowed β+ Emitter 14O

    Laffoley A. T.


    Full Text Available The half-life of 14O, a superallowed Fermi β+ emitter, has been determined via simultaneous γ and β counting experiments at TRIUMF’s Isotope Separator and Accelerator facility. Following the implantation of 14O samples at the center of the 8π spectrometer, a γ counting measurement was performed by detecting the 2313 keV γ-rays emitted from the first excited state of the daughter 14N using 20 high-purity germanium (HPGe detectors. A simultaneous β counting experiment was performed using a fast plastic scintillator positioned directly behind the implantation site. The results, T½(γ = 70:632 ± 0:094 s and T½(β = 70:610 ± 0:030 s, are consistent with one another and, together with eight previous measurements, establish a new average for the 14O half-life of T½ = 70:619 ± 0:011 s with a reduced χ2 of 0.99.

  11. Protein HESylation for half-life extension: synthesis, characterization and pharmacokinetics of HESylated anakinra.

    Liebner, Robert; Mathaes, Roman; Meyer, Martin; Hey, Thomas; Winter, Gerhard; Besheer, Ahmed


    Half-life extension (HLE) is becoming an essential component of the industrial development of small-sized therapeutic peptides and proteins. HESylation(®) is a HLE technology based on coupling drug molecules to the biodegradable hydroxyethyl starch (HES). In this study, we report on the synthesis, characterization and pharmacokinetics of HESylated anakinra, where anakinra was conjugated to propionaldehyde-HES using reductive amination, leading to a monoHESylated protein. Characterization using size exclusion chromatography and dynamic light scattering confirmed conjugation and the increase in molecular size, while Fourier transform infrared spectroscopy showed that the secondary structure of the conjugate was not affected by coupling. Meanwhile, microcalorimetry and aggregation studies showed a significant increase in protein stability. Surface plasmon resonance and microscale thermophoresis showed that the conjugate retained its nanomolar affinity, and finally, the pharmacokinetics of the HESylated protein exhibited a 6.5-fold increase in the half-life, and a 45-fold increase in the AUC. These results indicate that HESylation(®) is a promising HLE technology.

  12. Determination of half-life and photon emission probabilities of (65)Zn.

    Luca, Aurelian; Amiot, Marie-Noëlle; Morel, Jean


    A (65) Zn radioactive solution standardized by an absolute measurement method at Laboratoire National Henri Becquerel (LNHB), was sent to Bureau International des Poids et Mesures (BIPM), in order to include the results in their database. The activity value determined at BIPM was in good agreement with that stated by LNHB (the difference was 0.3%). Additional measurements of (65) Zn activity and half-life were also carried out, by using a 4pigamma ionization chamber; the half-life value proposed by this work: 244.15 (10) days, is consistent to others reported in the literature. The spectra analysis was performed by gamma-ray spectrometry with high-purity germanium detectors, with the aim to improve the accuracy of the photon emission probabilities values of this nuclide. The determined photon emission probabilities are 0.498 for the 1115 ke V gamma-ray, 0.347 and 0.0479 for the X-rays Cu-K(alpha) and Cu-K(beta); the associated uncertainties are 0.4%, 0.9% and 1.1%, respectively.

  13. Isolation of human anti-serum albumin Fab antibodies with an extended serum-half life.

    Kang, Hyeon-Ju; Kim, Hye-Jin; Cha, Sang-Hoon


    The serum albumin (SA) has been exploited to generate long-acting biotherapeutics by taking advantage of the FcRn-mediated recycling mechanism in a direct or an indirect way. Since Fab fragments have been proven to be clinically safe for human usage, we assumed that human anti-SA Fab antibodies could have a great potential as a carrier molecule to extend the serum half-life of therapeutic proteins. We, herein, had attempted to isolate anti-SA Fab antibodies from HuDVFab-8L antibody library via a phage display technology, and identified eight discrete human Fab antibodies. One of the Fab antibodies, SL335, showed the strongest binding reactivity to human SA with nM range of affinity at both pH 6 and pH 7.4, and cross-reacted to SAs from various species including rat, mouse, canine and monkey. The in vivo pharmacokinetic assay using a rat model indicated that SL335 has approximately 10 fold longer serum half-life and 26 to 44-fold increase in AUC0 → ∞ compared to the negative control Fab molecule in both intravenous and subcutaneous administrations. Knowing that Fabs have proven to be safe in clinics for a long time, SL335 seems to have a great potential in generating long-acting protein drugs by tagging effector molecules with either chemical conjugation or genetic fusion.

  14. Estimating the biological half-life for radionuclides in homoeothermic vertebrates: a simplified allometric approach

    Beresford, N.A. [Lancaster Environment Centre, NERC Centre for Ecology and Hydrology, Lancaster (United Kingdom); Vives i Batlle, J. [Belgian Nuclear Research Centre, Mol (Belgium)


    The application of allometric, or mass-dependent, relationships within radioecology has increased with the evolution of models to predict the exposure of organisms other than man. Allometry presents a method of addressing the lack of empirical data on radionuclide transfer and metabolism for the many radionuclide-species combinations which may need to be considered. However, sufficient data across a range of species with different masses are required to establish allometric relationships and this is not always available. Here, an alternative allometric approach to predict the biological half-life of radionuclides in homoeothermic vertebrates which does not require such data is derived. Biological half-life values are predicted for four radionuclides and compared to available data for a range of species. All predictions were within a factor of five of the observed values when the model was parameterised appropriate to the feeding strategy of each species. This is an encouraging level of agreement given that the allometric models are intended to provide broad approximations rather than exact values. However, reasons why some radionuclides deviate from what would be anticipated from Kleiber's law need to be determined to allow a more complete exploitation of the potential of allometric extrapolation within radioecological models. (orig.)

  15. Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative Half-life Values and Characterizing Pesticide Degradation

    Results of the degradation kinetics project and describes a general approach for calculating and selecting representative half-life values from soil and aquatic transformation studies for risk assessment and exposure modeling purposes.

  16. Pile-up corrections for high-precision superallowed {beta} decay half-life measurements via {gamma}-ray photopeak counting

    Grinyer, G.F. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada)], E-mail:; Svensson, C.E.; Andreoiu, C. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Andreyev, A.N. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Austin, R.A.E. [Department of Astronomy and Physics, St. Mary' s University, Halifax, NS, B3H 3C3 (Canada); Ball, G.C. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Bandyopadhyay, D. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Chakrawarthy, R.S. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Finlay, P. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Garrett, P.E. [Department of Physics, University of Guelph, Guelph, Ont, Canada N1G 2W1 (Canada); TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Hackman, G. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Hyland, B. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Kulp, W.D. [School of Physics, Georgia Institute of Technology, Atlanta, GA 30332 0430 (United States); Leach, K.G. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Leslie, J.R. [Department of Physics, Queen' s University, Kingston, Ont., K7L 3N6 (Canada); Morton, A.C.; Pearson, C.J. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Phillips, A.A. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Sarazin, F. [Department of Physics, Colorado School of Mines, Golden, CO 80401 (United States); Schumaker, M.A. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada)] (and others)


    A general technique that corrects {gamma}-ray gated {beta} decay-curve data for detector pulse pile-up is presented. The method includes corrections for non-zero time-resolution and energy-threshold effects in addition to a special treatment of saturating events due to cosmic rays. This technique is verified through a Monte Carlo simulation and experimental data using radioactive beams of {sup 26}Na implanted at the center of the 8{pi}{gamma}-ray spectrometer at the ISAC facility at TRIUMF in Vancouver, Canada. The {beta}-decay half-life of {sup 26}Na obtained from counting 1809-keV {gamma}-ray photopeaks emitted by the daughter {sup 26}Mg was determined to be T{sub 1/2}=1.07167{+-}0.00055s following a 27{sigma} correction for detector pulse pile-up. This result is in excellent agreement with the result of a previous measurement that employed direct {beta} counting and demonstrates the feasibility of high-precision {beta}-decay half-life measurements through the use of high-purity germanium {gamma}-ray detectors. The technique presented here, while motivated by superallowed-Fermi {beta} decay studies, is general and can be used for all half-life determinations (e.g. {alpha}-, {beta}-, X-ray, fission) in which a {gamma}-ray photopeak is used to select the decays of a particular isotope.

  17. Development of a time-variable nuclear pulser for half life measurements

    Zahn, Guilherme S.; Domienikan, Claudio; Carvalhaes, Roberto P. M.; Genezini, Frederico A. [Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP. P.O. Box 11049, Sao Paulo, 05422-970 (Brazil)


    In this work a time-variable pulser system with an exponentially-decaying pulse frequency is presented, which was developed using the low-cost, open-source Arduino microcontroler plataform. In this system, the microcontroller produces a TTL signal in the selected rate and a pulse shaper board adjusts it to be entered in an amplifier as a conventional pulser signal; both the decay constant and the initial pulse rate can be adjusted using a user-friendly control software, and the pulse amplitude can be adjusted using a potentiometer in the pulse shaper board. The pulser was tested using several combinations of initial pulse rate and decay constant, and the results show that the system is stable and reliable, and is suitable to be used in half-life measurements.

  18. Half-life of each dioxin and PCB congener in the human body

    Ogura, Isamura [National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan)


    It is well known that dioxin and PCB congeners accumulate in the human body. For assessing their toxicological risk, it is important to know the half-life of each congener in the human body. This study summarizes the overall half-lives of congeners in humans as reported in the literature, and compares them with the half-lives due to fecal and sebum excretions, as estimated by data on the concentrations of congeners in feces and sebum in the literature. In addition, the overall half-lives of congeners for the general Japanese population were estimated from the data on dietary intakes and concentrations in the human body reported by the municipalities.

  19. Precise Half-Life Measurement of the Superallowed Beta+ Emitter 26Si

    Iacob, V E; Banu, A; Chen, L; Golovko, V V; Goodwin, J; Horvat, V; Nica, N; Park, H I; Trache, L; Tribble, R E


    We have measured the half-life of the superallowed 0+ -to- 0+ beta+ emitter 26Si to be 2245.3(7) ms. We used pure sources of 26Si and employed a high-efficiency gas counter, which was sensitive to positrons from both this nuclide and its daughter 26mAl. The data were analyzed as a linked parent-daughter decay. To contribute meaningfully to any test of the unitarity of the Cabibbo-Kobayashi-Maskawa (CKM) matrix, the ft value of a superallowed transition must be determined to a precision of 0.1% or better. With a precision of 0.03% the present result is more than sufficient to be compatable with that requirement. Only the branching ratio now remains to be measured precisely before a +/-0.1% ft value can be obtained for the superallowed transition from 26Si.

  20. Half-life measurement of neutron-rich isotope 237Th


    60 MeV/u 18O ions were used to bombard natural uranium targets, and the heavy neutron-rich isotope 237Th was produced via multi-nucleon transfer reaction and dissipative fragmentation of the heavy target. A relatively fast radiochcmical procedure was used to separate thorium from the mixture of uranium and complex reaction products. The chemically separated thorium fractions were studied by the γ-ray spectroscopic method. The behaviors of the growth and decay of 853.7 and 865.0 keV γ rays of 237pa decay were observed. Thc half-life of 237Th was determined to be 4.69±0.60 min.

  1. The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions.

    Glick, Matthew; Biddle, Perry; Jantzi, Josh; Weaver, Samantha; Schirch, Doug


    Clinical research is currently exploring the validity of the anti-tumor candidate 3-bromopyruvate (3-BP) as a novel treatment for several types of cancer. However, recent publications have overlooked rarely-cited earlier work about the instability of 3-BP and its decay to 3-hydroxypyruvate (3-HP) which have obvious implications for its mechanism of action against tumors, how it is administered, and for precautions when preparing solutions of 3-BP. This study found the first-order decay rate of 3-BP at physiological temperature and pH has a half-life of only 77 min. Lower buffer pH decreases the decay rate, while choice of buffer and concentration do not affect it. A method for preparing more stable solutions is also reported.

  2. ORIGEN-S Decay Data Library and Half-Life Uncertainties

    Hermann, O.W.


    The results of an extensive update of the decay data of the ORIGEN-S library are presented in this report. The updated decay data were provided for both the ORIGEN-S and ORIGEN2 libraries in the same project. A complete edit of the decay data plus the available half-life uncertainties are included in Appendix A. A detailed description of the types of data contained in the library, the format of the library, and the data sources are also presented. Approximately 24% of the library nuclides are stable, 66% were updated from ENDF/B-VI, about 8% were updated from ENSDF, and the remaining 2% were not updated. Appendix B presents a listing of percentage changes in decay heat from the old to the updated library for all nuclides containing a difference exceeding 1% in any parameter.

  3. Precise half-life values for two neutrino double beta decay

    Barabash, A S


    All existing "positive" results on two neutrino double beta decay in different nuclei were analyzed. Using the procedure recommended by the Particle Data Group, weighted average values for half-lives of $^{48}$Ca, $^{76}$Ge, $^{82}$Se, $^{96}$Zr, $^{100}$Mo, $^{100}$Mo - $^{100}$Ru ($0^+_1$), $^{116}$Cd, $^{130}$Te, $^{150}$Nd, $^{150}$Nd - $^{150}$Sm($0^+_1$) and $^{238}$U were obtained. Existing geochemical data were analyzed and recommended values for half-lives of $^{128}$Te, $^{130}$Te and $^{130}$Ba are proposed. Given the measured half-life values, nuclear matrix elements were calculated. I recommend the use of these results as the most currently reliable values for the half-lives and nuclear matrix elements.

  4. Average and recommended half-life values for two neutrino double beta decay

    Barabash, A S


    All existing positive results on two neutrino double beta decay in different nuclei were analyzed. Using the procedure recommended by the Particle Data Group, weighted average values for half-lives of $^{48}$Ca, $^{76}$Ge, $^{82}$Se, $^{96}$Zr, $^{100}$Mo, $^{100}$Mo - $^{100}$Ru ($0^+_1$), $^{116}$Cd, $^{130}$Te, $^{136}$Xe, $^{150}$Nd, $^{150}$Nd - $^{150}$Sm ($0^+_1$) and $^{238}$U were obtained. Existing geochemical data were analyzed and recommended values for half-lives of $^{128}$Te, and $^{130}$Ba are proposed. Given the measured half-life values, nuclear matrix elements were calculated using latest (more reliable and precise) values for phase space factor. Finally, previous results (PRC 81 (2010) 035501) were up-dated and results for $^{136}$Xe were added.

  5. Precise half-life measurements for $^{38}$Ca and $^{39}$Ca

    Blank, B; Demonchy, C-E; Borge, M J G; Matea, I; Munoz, F; Huikari, J; Dominguez-Reyes, R; Plaisir, C; Sturm, S; Canchel, G; Delahaye, P; Audirac, L; Fraile, L M; Serani, L; Lunney, D; Pedroza, J-L; Bey, A; Souin, J; Hui, Tran Trong; Delalee, F; Tengblad, O; Wenander, F


    The half-lives of Ca-38 and Ca-39 have been measured at ISOLDE of CERN. The REXTRAP facility was used to prepare ultra-clean samples of radioactive nuclei for precision decay spectroscopy. Ca-38 is one of the T-z = -1, 0(+). 0(+) beta-emitting nuclides used to determine the vector coupling constant of the weak interaction and the V-ud quark-mixing matrix element. The result obtained, T-1/2 = 443.8(19) ms, is four times more precise than the average of previous measurements. For Ca-39, a half-life of T-1/2 = 860.7(10) ms is obtained, a result in agreement with the average value from the literature.

  6. Alpha-decay half-life semiempirical relationships with self-improving parameters

    Poenaru, D.N.; Ivascu, M.; Mazilu, D. (Institutul Central de Fizica, Bucharest (Romania))


    From the alpha decay Q-values, the partial half-life T is estimated by using five semiempirical relationships. The parameters of these formulae have been obtained from a fit with a given set of experimental data on four groups of alpha emitters: even-even, even-odd, odd-even and odd-odd. For each nuclide only the strongest transition is considered and the data are automatically sorted into the four groups mentioned above. There are three options: one can use either the present set of parameter values, a new one given as input data, or new values computed by using a better set of experimental data (more accurate or more complete). For each group of nuclides, up to 8 (or 9) families of curves could be plotted, optionally, with the line printer.

  7. Measurement of the 135Cs half-life with accelerator mass spectrometry and inductively coupled plasma mass spectrometry

    MacDonald, C. M.; Cornett, R. J.; Charles, C. R. J.; Zhao, X. L.; Kieser, W. E.


    The isotope 135Cs is quoted as having a half-life of 2.3 Myr. However, there are three published values ranging from 1.8 to 3 Myr. This research reviews previous measurements and reports a new measurement of the half-life using newly developed accelerator mass spectrometry (AMS) and inductively coupled plasma mass spectrometry (ICPMS) techniques along with β and γ radiometric analysis. The half-life was determined to be (1.6 ±0.6 ) ×106 yr by AMS and (1.3 ±0.2 ) ×106 yr by ICPMS with 95% confidence. The two values agree with each other but differ from the accepted value by ˜40 % .

  8. Towards a Measurement of the Half-Life of {sup 60}Fe for Stellar and Early Solar System Models

    Ostdiek, K.; Anderson, T.; Bauder, W.; Bowers, M.; Collon, P.; Dressler, R.; Greene, J.; Kutschera, W.; Lu, W.; Paul, M.


    Radioisotopes, produced in stars and ejected into the Interstellar Medium, are important for constraining stellar and early Solar System (ESS) models. In particular, the half-life of the radioisotope, Fe-60, can have an impact on calculations for the timing for ESS events, the distance to nearby Supernovae, and the brightness of individual, non-steady-state Fe gamma ray sources in the Galaxy. A half-life measurement has been undertaken at the University of Notre Dame and measurements of the Fe-60/Fe-56 concentration of our samples using Accelerator Mass Spectrometry has begun. This result will be coupled with an activity measurement of the isomeric decay in Co-60, which is the decay product of Fe. Preliminary half-life estimates of (2.53 +/- 0.24) x 10(6) years seem to confirm the recent measurement by Rugel et al. (2009). (C) 2015 Elsevier B.V. All rights reserved.

  9. Half-life of the electron-capture decay of 97Ru: Precision measurement shows no temperature dependence

    Goodwin, J R; Iacob, V E; Hardy, J C; 10.1103/PhysRevC.80.045501


    We have measured the half-life of the electron-capture (ec) decay of 97Ru in a metallic environment, both at low temperature (19K), and also at room temperature. We find the half-lives at both temperatures to be the same within 0.1%. This demonstrates that a recent claim that the ec decay half-life for 7Be changes by $0.9% +/- 0.2% under similar circumstances certainly cannot be generalized to other ec decays. Our results for the half-life of 97Ru, 2.8370(14)d at room temperature and 2.8382(14)d at 19K, are consistent with, but much more precise than, previous room-temperature measurements. In addition, we have also measured the half-lives of the beta-emitters 103Ru and 105Rh at both temperatures, and found them also to be unchanged.

  10. Towards a measurement of the half-life of {sup 60}Fe for stellar and early Solar System models

    Ostdiek, K.; Anderson, T. [University of Notre Dame, Notre Dame, IN 46556 (United States); Bauder, W. [University of Notre Dame, Notre Dame, IN 46556 (United States); Argonne National Laboratory, 9700 South Cass Avenue, Lemont, IL 60439 (United States); Bowers, M.; Collon, P. [University of Notre Dame, Notre Dame, IN 46556 (United States); Dressler, R. [Paul Scherrer Institute – Laboratory for Radiochemistry and Environmental Chemistry, 5232 Villigen (Switzerland); Greene, J. [Argonne National Laboratory, 9700 South Cass Avenue, Lemont, IL 60439 (United States); Kutschera, W. [Vienna Environmental Research Accelerator Laboratory, Waehringer Strasse 17, 1090 Vienna (Austria); Lu, W. [University of Notre Dame, Notre Dame, IN 46556 (United States); Paul, M. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel); Robertson, D. [University of Notre Dame, Notre Dame, IN 46556 (United States); Schumann, D. [Paul Scherrer Institute – Laboratory for Radiochemistry and Environmental Chemistry, 5232 Villigen (Switzerland); Skulski, M. [University of Notre Dame, Notre Dame, IN 46556 (United States); Wallner, A. [The Australian National University, Canberra, ACT 0200 (Australia)


    Radioisotopes, produced in stars and ejected into the Interstellar Medium, are important for constraining stellar and early Solar System (ESS) models. In particular, the half-life of the radioisotope, {sup 60}Fe, can have an impact on calculations for the timing for ESS events, the distance to nearby Supernovae, and the brightness of individual, non-steady-state {sup 60}Fe gamma ray sources in the Galaxy. A half-life measurement has been undertaken at the University of Notre Dame and measurements of the {sup 60}Fe/{sup 56}Fe concentration of our samples using Accelerator Mass Spectrometry has begun. This result will be coupled with an activity measurement of the isomeric decay in {sup 60}Co, which is the decay product of {sup 60}Fe. Preliminary half-life estimates of (2.53 ± 0.24) × 10{sup 6} years seem to confirm the recent measurement by Rugel et al. (2009).

  11. New evaluation of alpha decay half-life of {sup 190}Pt isotope for the Pt-Os dating system

    Tavares, O.A.P.; Medeiros, E.L. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Terranova, M.L. [Universita degli Studi di Roma Tor Vergata (Italy). Dipt. di Scienze e Tecnologie Chimiche; Istituto Nazionale di Fisica Nucleare (INFN), Rome (Italy)


    A semiempirical model based on the quantum mechanical tunnelling mechanism of alpha emission from nuclei has been used to evaluate the half-life of the Pt isotopes. For the important naturally occurring {sup 190}Pt isotope, the radiogenic parent in the {sup 190} Pt {yields} {sup 186}Os dating system, the model yielded a half-life value of (3.7{+-} 0.3) versus 10{sup 11} y. This is comparable to (3.2{+-}0.1) versus 10{sup 11} y which was obtained in the last direct counting experiment to measure the alpha activity of {sup 190}Pt (Tavares and Terranova, Rad. Measurem. 27 (1997) 19). A literature survey of available alpha decay half-life values for {sup 190}Pt isotope is also reported. The significant discrepancies found between data obtained by direct counting, indirect geological methods and different calculation models are analysed and discussed. (author)

  12. The half-life of Ascaris lumbricoides prevalence in Japanese school children.

    Kurosawa, Carmen Miwa; Ito, Takehiko; Takaki, Jiro; Wang, Bin-Ling; Wang, Da-Hong; Takigawa, Tomoko; Ogino, Keiki


    In the present study, we examined the dynamic of school-health-based parasite control and the related socio-economic influences. This is an ecological study based on data from 46 prefectures in Japan. The exponential decay of Ascaris lumbricoides prevalence was calculated by iterative least-squares method. Pearson's correlation and multiple linear regression model analysis were performed to assess the associations between the prevalence of Ascaris lumbricoides in Japanese school children and socio-economic variables such as the prefecture income per capita, the percentage of primary industry, the population density per 1 km2, the diffusion rate of population under water supply, and the percentage of upper secondary school enrollment. The results indicated that the parasite carrier rate was higher in younger students. The half-life of Ascaris lumbricoides prevalence was approximately 3 years with significant variation among prefectures. Multiple regression analyses showed that the decrease of infection in elementary and lower secondary school children had a significant positive association with primary industry and a significant negative association with prefecture income per capita. The school-health-based parasite intervention differs by prefecture and has changed over time according to the respective prefectural stage of economic development.

  13. Accurate measurements of {sup 129}I concentration by isotope dilution using MC-ICPMS for half-life determination

    Isnard, Helene; Nonell, Anthony; Marie, Mylene [Commissariat a l' Energie Atomique et aux Energies alternatives (CEA), Gif Sur Yvette (France). DEN, DPC, SEARS, LANIE; Chartier, Frederic [Commissariat a l' Energie Atomique et aux Energies alternatives (CEA), Gif Sur Yvette (France). DEN, DPC


    Determining the {sup 129}I concentration, a long-lived radionuclide present in spent nuclear fuel, is a major issue for nuclear waste disposal purpose. {sup 129}I also has to be measured in numerous environmental, nuclear and biological samples. To be able to accurately determine the {sup 129}I concentration, an analytical method based on the use of a multicollector-inductively coupled plasma mass spectrometer (MC-ICPMS) combined with an isotope dilution technique using an {sup 127}I spike, was developed. First, the influence of different media (HNO{sub 3}, NaOH and TMAH) on natural {sup 127}I signal intensity and stability and on memory effects was studied. Then an analytical procedure was developed by taking into account the correction of blanks and interferences. Tellurium was chosen for instrumental mass bias correction, as no certified standards with suitable {sup 127}I/{sup 129}I ratio are available. Finally, the results, reproducibility and uncertainties obtained for the {sup 129}I concentration determined by isotope dilution with a {sup 127}I spike are presented and discussed. The final expanded relative uncertainty obtained for the iodine-129 concentration was lower than 0.7% (k = 1). This precise {sup 129}I determination in association with further activity measurements of this nuclide on the same sample will render it possible to determine a new value of the {sup 129}I half-life with a reduced uncertainty (0.76%, k = 1).

  14. High-precision half-life and branching-ratio measurements for superallowed Fermi β+ emitters at TRIUMF – ISAC

    Laffoley A. T.


    Full Text Available A program of high-precision half-life and branching-ratio measurements for superallowed Fermi β emitters is being carried out at TRIUMF’s Isotope Separator and Accelerator (ISAC radioactive ion beam facility. Recent half-life measurements for the superallowed decays of 14O, 18Ne, and 26Alm, as well as branching-ratio measurements for 26Alm and 74Rb are reported. These results provide demanding tests of the Standard Model and the theoretical isospin symmetry breaking (ISB corrections in superallowed Fermi β decays.

  15. Measurement of the Double Beta Decay Half-life of 130Te with the NEMO-3 Detector

    Arnold, R; Baker, J; Barabash, A S; Basharina-Freshville, A; Blondel, S; Bongrand, M; Broudin-Bay, G; Brudanin, V; Caffrey, A J; Chapon, A; Chauveau, E; Durand, D; Egorov, V; Flack, R; Garrido, X; Grozier, J; Guillon, B; Hubert, Ph; Jackson, C M; Jullian, S; Kauer, M; Klimenko, A; Kochetov, O; Konovalov, S I; Kovalenko, V; Lalanne, D; Lamhamdi, T; Lang, K; Liptak, Z; Lutter, G; Mamedov, F; Marquet, Ch; Martin-Albo, J; Mauger, F; Mott, J; Nachab, A; Nemchenok, I; Nguyen, C H; Nova, F; Novella, P; Ohsumi, H; Pahlka, R B; Perrot, F; Piquemal, F; Reyss, J L; Richards, B; Ricol, J S; Saakyan, R; Sarazin, X; Shitov, Yu; Simard, L; Šimkovic, F; Smolnikov, A; Söldner-Rembold, S; Štekl, I; Suhonen, J; Sutton, C S; Szklarz, G; Thomas, J; Timkin, V; Torre, S; Tretyak, V I; Umatov, V; Vála, L; Vanyushin, I; Vasiliev, V; Vorobel, V; Vylov, T; Zukauskas, A


    This Letter reports results from the NEMO-3 experiment based on an exposure of 1275 days with 661g of 130Te in the form of enriched and natural tellurium foils. With this data set the double beta decay rate of 130Te is found to be non-zero with a significance of 7.7 standard deviations and the half-life is measured to be T1/2 = (7.0 +/- 0.9(stat) +/- 1.1(syst)) x 10^{20} yr. This represents the most precise measurement of this half-life yet published and the first real-time observation of this decay.

  16. Clinical utility and patient perspectives on the use of extended half-life rFIXFc in the management of hemophilia B

    Miguelino MG


    Full Text Available Maricel G Miguelino, Jerry S Powell Division of Hematology and Oncology, University of California Davis Medical Center, Sacramento, CA, USA Abstract: Hemophilia B is an X-linked genetic disease caused by mutation of the gene for coagulation protein factor IX (FIX, with an incidence of approximately once every 30,000 male births in all populations and ethnic groups. When severe, the disease leads to spontaneous life threatening bleeding episodes. When untreated, most patients die from bleeding complications before 25 years of age. Current therapy requires frequent intravenous infusions of therapeutic recombinant or plasma-derived protein concentrates containing FIX. Most patients administer the infusions at home every few days, and must limit their physical activities to avoid abnormal bleeding when the FIX activity levels are below normal. After completing the pivotal Phase III clinical trial, a new therapeutic FIX preparation that has been engineered for an extended half-life in circulation, received regulatory approval in March 2014 in Canada and the US. This new FIX represents a major therapeutic advance for patients with hemophilia B. The half-life is prolonged due to fusion of the native FIX molecule with the normal constant region of immunoglobulin G. This fusion molecule then follows the normal immunoglobulin recirculation pathways through endothelial cells, resulting in prolonged times in circulation. In the clinical trials, over 150 patients successfully used eftrenonacog alfa regularly for more than 1 year to prevent spontaneous bleeding, to successfully treat any bleeding episodes, and to provide effective coagulation for major surgery. All infusions were well tolerated and effective, with no inhibitors detected and no safety concerns. This promising therapy should allow patients to use fewer infusions to maintain appropriate FIX activity levels in all clinical settings. Keywords: factor IX, hemophilia B, prophylaxis, genetic

  17. Estimation of biological half-life of tritium in coastal region of India.

    Singh, Vishwanath P; Pai, R K; Veerender, D D; Vishnu, M S; Vijayan, P; Managanvi, S S; Badiger, N M; Bhat, H R


    The present study estimates biological half-life (BHL) of tritium by analysing routine bioassay samples of radiation workers. During 2007-2009 year, 72,100 urine bioassay samples of the workers were analysed by liquid scintillation counting technique for internal dose monitoring for tritium. Two hundred and two subjects were taken for study with minimum 3 μCiL(-1) tritium uptake in their body fluid. The BHL of tritium of subjects ranges from 1 to 16 d with an average of 8.19 d. Human data indicate that the biological retention time ranges from 4 to 18 d with an average of 10 d. The seasonal variations of the BHL of tritium are 3.09 ± 1.48, 6.87 ± 0.58 and 5.73 ± 0.76 d (mean ± SD) for summer, winter and rainy seasons, respectively, for free water tritium in the coastal region of Karnataka, India, which shows that the BHL in summer is twice that of the winter season. Also three subjects showed the BHL of 101.73-121.09 d, which reveals that organically bound tritium is present with low tritium uptake also. The BHL of tritium for all age group of workers is observed independent of age and is shorter during April to May. The distribution of cumulative probability vs. BHL of tritium shows lognormal distribution with a geometric mean of 9.11 d and geometric standard deviation of 1.77 d. The study of the subjects is fit for two-compartment model and also an average BHL of tritium is found similar to earlier studies.

  18. Extending the Serum Half-Life of G-CSF via Fusion with the Domain III of Human Serum Albumin

    Shuqiang Zhao


    Full Text Available Protein fusion technology is one of the most commonly used methods to extend the half-life of therapeutic proteins. In this study, in order to prolong the half-life of Granulocyte colony stimulating factor (G-CSF, the domain III of human serum albumin (3DHSA was genetically fused to the N-terminal of G-CSF. The 3DHSA-G-CSF fusion gene was cloned into pPICZαA along with the open reading frame of the α-factor signal under the control of the AOX1 promoter. The recombinant expression vector was transformed into Pichia pastoris GS115, and the recombinant strains were screened by SDS-PAGE. As expected, the 3DHSA-G-CSF showed high binding affinity with HSA antibody and G-CSF antibody, and the natural N-terminal of 3DHSA was detected by N-terminal sequencing. The bioactivity and pharmacokinetic studies of 3DHSA-G-CSF were respectively determined using neutropenia model mice and human G-CSF ELISA kit. The results demonstrated that 3DHSA-G-CSF has the ability to increase the peripheral white blood cell (WBC counts of neutropenia model mice, and the half-life of 3DHSA-G-CSF is longer than that of native G-CSF. In conclusion, 3DHSA can be used to extend the half-life of G-CSF.

  19. Precise measurement of the 222Rn half-life: A probe to monitor the stability of radioactivity

    E. Bellotti


    Full Text Available We give the results of a study on the 222Rn decay we performed in the Gran Sasso Laboratory (LNGS by detecting the gamma rays from the radon progeny. The motivation was to monitor the stability of radioactivity measuring several times per year the half-life of a short lifetime (days source instead of measuring over a long period the activity of a long lifetime (tens or hundreds of years source. In particular, we give a possible reason of the large periodical fluctuations in the count rate of the gamma rays due to radon inside a closed canister which has been described in literature and which has been attributed to a possible influence of a component in the solar irradiation affecting the nuclear decay rates. We then provide the result of four half-life measurements we performed underground at LNGS in the period from May 2014 to January 2015 with radon diffused into olive oil. Briefly, we did not measure any change of the 222Rn half-life with a 8⋅10−5 precision. Finally, we provide the most precise value for the 222Rn half-life: 3.82146(16stat(4syst days.

  20. Brief report : enzyme inducers reduce elimination half-life after a single dose of nevirapine in healthy women

    L'homme, R.F.A.; Dijkema, T.; Ven, A.J.A.M. van der; Burger, D.M.


    OBJECTIVE: Single-dose nevirapine (SD-NVP) to prevent mother-to-child transmission (MTCT) of HIV is associated with development of NVP resistance, probably because of its long half-life in combination with a low genetic barrier to resistance. The objective of this study was to find enzyme inducers t

  1. Screening and ranking of POPs for global half-life: QSAR approaches for prioritization based on molecular structure.

    Gramatica, Paola; Papa, Ester


    Persistence in the environment is an important criterion in prioritizing hazardous chemicals and in identifying new persistent organic pollutants (POPs). Degradation half-life in various compartments is among the more commonly used criteria for studying environmental persistence, but the limited availability of experimental data or reliable estimates is a serious problem. Available half-life data for degradation in air, water, sediment, and soil, for a set of 250 organic POP-type chemicals, were combined in a multivariate approach by principal component analysis to obtain a ranking of the studied organic pollutants according to their relative overall half-life. A global half-life index (GHLI) applicable for POP screening purposes is proposed. The reliability of this index was verified in comparison with multimedia model results. This global index was then modeled as a cumulative end-point using a QSAR approach based on few theoretical molecular descriptors, and a simple and robust regression model externally validated for its predictive ability was derived. The application of this model could allow a fast preliminary identification and prioritization of not yet known POPs, just from the knowledge of their molecular structure. This model can be applied a priori also in the chemical design of safer and alternative non-POP compounds.

  2. A Fab-Selective Immunoglobulin-Binding Domain from Streptococcal Protein G with Improved Half-Life Extension Properties.

    Felix Unverdorben

    Full Text Available Half-life extension strategies have gained increasing interest to improve the pharmacokinetic and pharmacodynamic properties of protein therapeutics. Recently, we established an immunoglobulin-binding domain (IgBD from streptococcal protein G (SpGC3 as module for half-life extension. SpGC3 is capable of binding to the Fc region as well as the CH1 domain of Fab arms under neutral and acidic conditions.Using site-directed mutagenesis, we generated a Fab-selective mutant (SpGC3Fab to avoid possible interference with the FcRn-mediated recycling process and improved its affinity for mouse and human IgG by site-directed mutagenesis and phage display selections. In mice, this affinity-improved mutant (SpGC3FabRR conferred prolonged plasma half-lives compared with SpGC3Fab when fused to small recombinant antibody fragments, such as single-chain Fv (scFv and bispecific single-chain diabody (scDb. Hence, the SpGC3FabRR domain seems to be a suitable fusion partner for the half-life extension of small recombinant therapeutics.The half-life extension properties of SpGC3 can be retained by restricting binding to the Fab fragment of serum immunoglobulins and can be improved by increasing binding activity. The modified SpGC3 module should be suitable to extend the half-life of therapeutic proteins and, thus to improve therapeutic activity.

  3. The functional half-life of an mRNA depends on the ribosome spacing in an early coding region

    Pedersen, Margit; Nissen, Søren; Mitarai, Namiko


    supported the model. We thus suggest that translation-rate-mediated differences in the spacing between ribosomes in this early coding region is a parameter that determines the mRNAs functional half-life. We present a model that is in accordance with many earlier observations and that allows a prediction...... codons. When comparing the ribosome spacing at various segments of the mRNA to its functional half-life, we found a clear correlation between the functional mRNA half-life and the ribosome spacing in the mRNA region approximately between codon 20 and codon 45. From this finding, we predicted that inserts......Bacterial mRNAs are translated by closely spaced ribosomes and degraded from the 5'-end, with half-lives of around 2 min at 37 °C in most cases. Ribosome-free or "naked" mRNA is known to be readily degraded, but the initial event that inactivates the mRNA functionally has not been fully described...

  4. Precise measurement of the 222Rn half-life: a probe to monitor the stability of radioactivity

    Bellotti, E; Di Carlo, G; Laubenstein, M; Menegazzo, R


    We give the results of a study on the 222Rn decay we performed in the Gran Sasso Laboratory (LNGS) by detecting the gamma rays from the radon progeny. The motivation was to monitor the stability of radioactivity measuring several times per year the half-life of a short lifetime (days) source instead of measuring over a long period the activity of a long lifetime (tens or hundreds of years) source. In particular, we give the reason of the large periodical fluctuations in the count rate of the gamma rays due to radon inside a closed canister which has been described in literature and which has been attributed to a possible influence of a component in the solar irradiation affecting the nuclear decay rates. We then provide the result of four half-life measurements we performed underground at LNGS in the period from May 2014 to January 2015 with radon diffused into olive oil. Briefly, we did not measure any change of the 222Rn half-life with a 8*10^-5 precision. Finally, we provide the most precise value for the ...

  5. Activity measurement of 60Fe through the decay of 60mCo and confirmation of its half-life

    Ostdiek, Karen; Bauder, William; Bowers, Matthew; Clark, Adam; Collon, Philippe; Dressler, Rugard; Greene, John; Kutschera, Walter; Lu, Wenting; Nelson, Austin; Paul, Michael; Robertson, Daniel; Schumann, Dorothea; Skulski, Michael


    The half-life of the neutron-rich nuclide, $^{60}\\text{Fe}$ has been in dispute in recent years. A measurement in 2009 published a value of $(2.62 \\pm 0.04)\\times10^{6}$ years, almost twice that of the previously accepted value from 1984 of $(1.49 \\pm 0.27)\\times10^{6}$ years. This longer half-life was confirmed in 2015 by a new measurement, resulting in a value of $(2.50 \\pm 0.12)\\times10^{6}$ years. All three half-life measurements used the grow-in of the $\\gamma$-ray lines in $^{60}\\text{Ni}$ from the decay of the ground state of $^{60\\text{g}}\\text{Co}$ (t$_{1/2}$=5.27 years) to determine the activity of a sample with a known number of $^{60}\\text{Fe}$ atoms. In contrast, the work presented here measured the $^{60}\\text{Fe}$ activity directly with the 58.6 keV $\\gamma$-ray line from the short-lived isomeric state of $^{60\\text{m}}\\text{Co}$ (t$_{1/2}$=10.5 minutes), thus being independent of any possible contamination from long-lived $^{60\\text{g}}\\text{Co}$. A fraction of the material from the 2015 exper...

  6. Role of ligand-dependent GR phosphorylation and half-life in determination of ligand-specific transcriptional activity.

    Avenant, Chanel; Ronacher, Katharina; Stubsrud, Elisabeth; Louw, Ann; Hapgood, Janet P


    A central question in glucocorticoid mechanism of action via the glucocorticoid receptor (GR) is what determines ligand-selective transcriptional responses. Using a panel of 12 GR ligands, we show that the extent of GR phosphorylation at S226 and S211, GR half-life and transcriptional response, occur in a ligand-selective manner. While GR phosphorylation at S226 was shown to inhibit maximal transcription efficacy, phosphorylation at S211 is required for maximal transactivation, but not for transrepression efficacy. Both ligand-selective GR phosphorylation and half-life correlated with efficacy for transactivation and transrepression. For both expressed and endogenous GR, in two different cell lines, agonists resulted in the greatest extent of phosphorylation and the greatest extent of GR downregulation, suggesting a link between these functions. However, using phosphorylation-deficient GR mutants we established that phosphorylation of the GR at S226 or S211 does not determine the rank order of ligand-selective GR transactivation. These results are consistent with a model whereby ligand-selective GR phosphorylation and half-life are a consequence of upstream events, such as ligand-specific GR conformations, which are maintained in the phosphorylation mutants.

  7. Improvements in 230Th dating, 230Th and 234U half-life values, and U-Th isotopic measurements by multi-collector inductively coupled plasma mass spectrometry

    Cheng, Hai; Lawrence Edwards, R.; Shen, Chuan-Chou; Polyak, Victor J.; Asmerom, Yemane; Woodhead, Jon; Hellstrom, John; Wang, Yongjin; Kong, Xinggong; Spötl, Christoph; Wang, Xianfeng; Calvin Alexander, E.


    We have developed techniques for measuring 234U and 230Th on Faraday cups with precisions of 1-3 epsilon units (1 ɛ-unit=1 part in 104) using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). Using a Thermo-Scientific Neptune with desolvation nebulization, we obtained ionization/transmission efficiencies of 1-2% for both U and Th. We set up protocols to correct for tailing, prepared U and Th gravimetric standards, tested a Th mass fractionation correction procedure based on U isotopes, and identified natural calcite samples likely to be in U-Th isotopic secular equilibrium. The measured atomic ratios, 234U/238U=54.970 (±0.019)×10-6 and 230Th/238U=16.916 (±0.018)×10-6, for these calcite samples were identical within errors (quoted 2σ uncertainties calculated combining all sources of error). Half-life values calculated from these ratios are consistent with previous values, but have much smaller errors: 245,620±260 a for 234U and 75,584±110 a for 230Th (quoted 2σ uncertainties calculated using all sources of error). In calculating a 230Th age, some of the systematic errors included in estimating the full error in the half-lives effectively cancel. Removing these uncertainties (uncertainty in the 238U half-life value, uncertainty in our gravimetric uranium and thorium standards, and uncertainty in the absolute isotopic composition of the uranium standard), yields effective uncertainties for the purposes of 230Th dating of ±70 a for the 234U half-life value and ±30 a for the 230Th half-life value. Under ideal circumstances, with our methods, the 2σ uncertainty in age, including uncertainty in half-life values is ±10 a at 10 ka, ±100 a at 130 ka, ±300 a at 200 ka, ±1 ka at 300 ka, ±2 ka at 400 ka, ±6 ka at 500 ka, and ±12 ka at 600 ka. The isotopic composition of a sample with an age determined independent of the Sanbao Cave ages, the observed co-variation between stalagmite δ18O and Northern Hemisphere summer insolation is

  8. Orthogonal assembly of a designed ankyrin repeat protein-cytotoxin conjugate with a clickable serum albumin module for half-life extension.

    Simon, Manuel; Frey, Raphael; Zangemeister-Wittke, Uwe; Plückthun, Andreas


    The generation of drug conjugates for safe and effective tumor targeting requires binding proteins tolerant to functionalization by rational engineering. Here, we show that Designed Ankyrin Repeat Proteins (DARPins), a novel class of binding proteins not derived from antibodies, can be used as building blocks for facile orthogonal assembly of bioconjugates for tumor targeting with tailored properties. DARPin Ec1, which targets the Epithelial Cell Adhesion Molecule (EpCAM), was genetically modified with a C-terminal cysteine for conjugation of the small molecule cytotoxin monomethylauristatin F (MMAF). In addition, it was N-terminally functionalized by metabolic introduction of the non-natural amino acid azidohomoalanine to enable linkage of site-specifically dibenzocyclooctyne-modified mouse serum albumin (MSA) for half-life extension using Cu(I)-free click chemistry. The conjugate MSA-Ec1-MMAF was assembled to obtain high yields of a pure and stable drug conjugate as confirmed by various analytical methods and in functional assays. The orthogonality of the assembly led to a defined reaction product and preserved the functional properties of all modules, including EpCAM-specific binding and internalization, FcRn binding mediated by MSA, and cytotoxic potency. Linkage of MMAF to the DARPin increased receptor-specific uptake of the drug while decreasing nonspecific uptake, and further coupling of the conjugate to MSA enhanced this effect. In mice, albumin conjugation increased the serum half-life from 11 min to 17.4 h, resulting in a more than 22-fold increase in the area-under-the-curve (AUC). Our data demonstrate the promise of the DARPin format for facile modular assembly of drug conjugates with improved pharmacokinetic performance for tumor targeting.

  9. Measurement of the half-life of 198Au in a non-metal: High-precision measurement shows no host-material dependence

    Goodwin, J R; Iacob, V E; Dibidad, A; Hardy, J C


    We have measured the half-life of the beta decay of 198Au to be 2.6948(9) d, with the nuclide sited in an insulating environment. Comparing this result with the half-life we measured previously with a metallic environment, we find the half-lives in both environments to be the same within 0.04%, thus contradicting a prediction that screening from a "plasma" of quasi-free electrons in a metal increases the half-life by as much as 7%.

  10. Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.

    Cignetto, Simona; Modica, Chiara; Chiriaco, Cristina; Fontani, Lara; Milla, Paola; Michieli, Paolo; Comoglio, Paolo M; Vigna, Elisa


    The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro, acting as full Met antagonists, impairing Met phosphorylation and activation of downstream signaling pathways. As a consequence, Met-mediated biological responses were inhibited, including anchorage-dependent and -independent cell growth. In vivo DCD-1 and DCD-2 showed a pharmacokinetic profile significantly improved over the original MvDN30, doubling the circulating half-life and reducing the clearance. In pre-clinical models of cancer, generated by injection of tumor cells or implant of patient-derived samples, systemic administration of the engineered molecules inhibited the growth of Met-addicted tumors.

  11. Shorter 146Sm half-life and revised 146Sm-142Nd ages of planetary mantle differentiation

    Kinoshita, N; Kashiv, Y; Collon, P; Deibel, C M; DiGiovine, B; Greene, J P; Henderson, D J; Jiang, C L; Marley, S T; Nakanishi, T; Pardo, R C; Rehm, K E; Robertson, D; Scott, R; Schmitt, C; Tang, X D; Vondrasek, R; Yokoyama, A


    The extinct short-lived nuclide 146Sm, synthesized in stellar events by the p-process, serves as both an astrophysical and geochemical chronometer through measurements of isotopic anomalies of its alpha-decay daughter 142Nd. Evidence of live 146Sm, quantitatively established for the early Solar System, constrains the time between p-process nucleosynthesis and condensation of the first solid materials. Samarium-146 is used also to date silicate mantle differentiation events in a number of planetary bodies, including Earth. We performed a new measurement of the 146Sm half-life and our result, t = 68\\pm7 (1sigma) million year (Ma), is significantly shorter than the value currently used for 146Sm-142Nd chronology (103\\pm5 Ma). We show here that the shorter 146Sm half-life value implies a higher initial Solar System ratio, (146Sm/144Sm)_0 = 0.0094\\pm0.0005 (2sigma), than the recently derived value 0.0085\\pm0.0007, or that used in most studies 0.008\\pm0.001. Planetary differentiation processes dated by 146Sm-142Nd ...

  12. In vitro digestion kinetics of excipients for lipid-based drug delivery and introduction of a relative lipolysis half life.

    Arnold, Yvonne E; Imanidis, Georgios; Kuentz, Martin


    Lipid-based drug delivery systems are widely used for enhancing the solubility of poorly water soluble drugs in the gastro-intestinal tract. Following oral intake, lipid systems undergo digestion in the stomach as well as the intestine. Lipolysis is here a complex process at the oil/water interface, influenced by numerous factors. To study the digestibility of nine excipients often used in lipid-based drug delivery systems. In addition, we introduced a mathematical model to describe in vitro lipolysis kinetics. A relative lipolysis half life was defined using the reference excipient medium-chain triglycerides. Using pH-stat equipment, the NaOH consumption was determined in an in vitro lipolysis assay. We identified two classes of excipients. Some additives were partially hydrolysed, whereas other excipients displayed complete lipolysis. For the latter class, a simplified mathematical model provided a good first approximation of initial lipolysis kinetics. Digestion characterization of excipients is important for the development of lipid-based delivery systems. The applied kinetic model and the concept of a relative lipolysis half life seemed to be promising tools for comparing in vitro lipolysis results.

  13. The half-life of the 1437 keV 11/2 sup - state in sup 97 Mo

    Kostova, L.G.; Andrejtscheff, W.; Kostov, L.K. (Bylgarska Akademiya na Naukite, Sofia (Bulgaria). Inst. za Yadrena Izsledvaniya i Yadrena Energetika); Funke, L.; Will, E. (Zentralinstitut fuer Kernforschung, Rossendorf (Germany)); Vdovin, A.I. (Joint Inst. for Nuclear Research, Dubna (Russia))


    Using the ({alpha}, n) reaction, the half-life of the first 11/2{sup -} level in {sup 97}Mo has been determined as T{sub 1/2}(1437.0 keV)=2.5{+-}0.3 ns by means of the pulsed beam method. The experimentally obtained B(M2) value between the h{sub 11/2} and g{sub 7/2} configurations in {sup 97}Mo has been satisfactorily described within the quasiparticle-phonon model using g{sub s}{sup eff}=0.6 g{sub s}{sup free} c{sub s}. Similar calculations and comparisons with experimental data have been performed also for {sup 95,99}Mo as well as for {sup 99}Ru and {sup 101}Pd. (orig.).

  14. The functional half-life of an mRNA depends on the ribosome spacing in an early coding region

    Pedersen, Margit; Nissen, Søren; Mitarai, Namiko;


    . Here, we characterize a determinant of the functional stability of an mRNA, which is located in the early coding region. Using literature values for the mRNA half-lives of variant lacZ mRNAs in Escherichia coli, we modeled how the ribosome spacing is affected by the translation rate of the individual...... of slowly translated codons before codon 20 or after codon 45 should shorten or prolong, respectively, the functional mRNA half-life by altering the ribosome density in the important region. These predictions were tested on eight new lacZ variants, and their experimentally determined mRNA half-lives all...

  15. 209Tl half-life and gamma-ray measurements of radionuclides belonging to the (4 n + 1) decay chain

    Ardisson, G.; Barci, V.; El Samad, O.


    Gamma-ray spectra of radiochemically separated 221Fr, 213Bi and 209Tl sources were measured using coaxial and planar HPGe detectors. The energies and emission probabilities of eight new gamma-ray transitions were observed in the decay of 209Tl; a half-life of (2.161±0.007) min was measured. Twenty-two gamma-rays have been attributed to the β-decay of 213Bi, of which 17 are new with respect to previous studies. The 213Po level scheme was determined using γ-γ coincidence measurements: eight excited states are proposed of which six are new. Preliminary measurements of the α-decay of 221Fr revealed the existence of 18 gamma-ray transitions of which eight are reported for the first time.

  16. Focus on the legislative approach to short half life radioactive hospital waste releasing.

    Petrucci, Caterina; Traino, Antonio Claudio


    We propose to summarize the advancements introduced by the new Directive 2013/59/Euratom concerning the concept of clearance, for which the radioactive medical waste represents a typical candidate. We also intend to spotlight disputable points in the regulatory scheme in force in Italy, as well to make a contribution to evaluate whether the practice of patients' urine storing, stated by it, can be regarded to be proper. With directing our interest to radionuclides used in Nuclear Medicine, we first present an overview of how the clearance concept, and that of exemption closely related to it, have been developed from the previous Directive 96/29 to the new one; then we describe the implementation of these concepts in the Italian legislation. Subsequently we estimate the exposure due both to keeping the effluent on site and to direct discharging it to the environment. In line with a well established international consensus, the Directive 2013/59 drives simple and harmonized regulation of clearance. On the contrary, some complexity and lack of consistency can be found in the framework of the national legislation affecting the radioactive medical waste handling. In addition the practice of excreta storing is disputed not to be really beneficial. The opportunity should be taken to make the whole system of these requirements simpler and more consistent and effective when it is revised to transpose the new Directive. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  17. The mysteriously variable half-life of dissolved organic matter in aquatic ecosystems: artefact or insight?

    Evans, Chris; Fovet, Ophelie; Jones, Tim; Jones, Davey; Moldan, Filip; Futter, Martyn


    Dissolved organic matter (DOM) fluxes from land to water represent an important loss term in the terrestrial carbon balance, a major pathway in the global carbon cycle, a significant influence on aquatic light, nutrient and energy regimes, and an important concern for drinking water production. Although freshwaters are now recognised as zones of active carbon cycling, rather than passive conduits for carbon transport, evidence regarding the magnitude of, and controls on, DOM cycling in aquatic systems is incomplete and in some cases seemingly contradictory, with DOM 'half-lives' ranging from a few days to many years. Bringing together experimental, isotopic, catchment mass balance and modelling data, we suggest that apparently conflicting results can be reconciled through understanding of differences in: i) the terrestrial sources of DOM within heterogeneous landscapes, and consequent differences in its reactivity and stoichiometry; ii) experimental methodologies (i.e. which reactions are actually being measured), and iii) the extent of prior transformation of DOM upstream of the point of study. We argue that rapid photo-degradation, particularly of peat-derived DOM, is a key process in headwaters, whilst apparently slow DOM turnover in downstream, agriculturally-influenced lakes and rivers can partly be explained by the offsetting effect of in situ DOM production. This production appears to be strongly constrained by nutrient supply, thus linking DOM turnover and composition to the supply of inorganic nutrient inputs from diffuse agricultural pollution, and also providing a possible mechanistic link between aquatic DOM production and terrestrial DOM breakdown via the mineralisation and re-assimilation of organic nutrients. A more complete conceptual understanding of these interlinked processes will provide an improved understanding of the sources and fate of aquatic DOM, its role in the global carbon cycle, and the impact of anthropogenic activities, for example

  18. pH-selective mutagenesis of protein-protein interfaces: in silico design of therapeutic antibodies with prolonged half-life.

    Spassov, Velin Z; Yan, Lisa


    Understanding the effects of mutation on pH-dependent protein binding affinity is important in protein design, especially in the area of protein therapeutics. We propose a novel method for fast in silico mutagenesis of protein-protein complexes to calculate the effect of mutation as a function of pH. The free energy differences between the wild type and mutants are evaluated from a molecular mechanics model, combined with calculations of the equilibria of proton binding. The predicted pH-dependent energy profiles demonstrate excellent agreement with experimentally measured pH-dependency of the effect of mutations on the dissociation constants for the complex of turkey ovomucoid third domain (OMTKY3) and proteinase B. The virtual scanning mutagenesis identifies all hotspots responsible for pH-dependent binding of immunoglobulin G (IgG) to neonatal Fc receptor (FcRn) and the results support the current understanding of the salvage mechanism of the antibody by FcRn based on pH-selective binding. The method can be used to select mutations that change the pH-dependent binding profiles of proteins and guide the time consuming and expensive protein engineering experiments. As an application of this method, we propose a computational strategy to search for mutations that can alter the pH-dependent binding behavior of IgG to FcRn with the aim of improving the half-life of therapeutic antibodies in the target organism.

  19. Comparison of serum immunoglobulin G half-life in dairy calves fed colostrum, colostrum replacer or administered with intravenous bovine plasma.

    Murphy, Jacob M; Hagey, Jill V; Chigerwe, Munashe


    In calves, passive immunity of immunoglobulins can be acquired through ingestion of colostrum or colostrum replacers. Plasma can been used to supplement immunoglobulins in healthy or sick calves. Serum half-life of colostral derived immuglobulin G (IgG) is estimated to be 20 days. Half-life of IgG is important in determining response to antigens and timing of vaccination in calves. To date studies evaluating half-life of colostrum replacer or plasma derived IgG are lacking. The objectives of this study were to compare the serum half-life of IgG derived from colostrum, colostrum replacer and plasma in dairy calves reared up to 35 days of age. Thirty Jersey calves were randomly assigned to receive colostrum or colostrum replacer by oroesophageal tubing or plasma by intravenous administration. Serum samples were collected at 2, 5, 7, 10, 14, 21, 28 and 35 days. Serum IgG concentrations were determined by radial immunodiffusion. The results indicated that half-life for IgG in colostrum fed (28.5 days) or plasma transfused calves (27.3 days) was longer than colostrum replacer fed calves (19.1 days). Further studies are required to evaluate pathogen specific immunoglobulins in order to recommend vaccination timing in calves fed colostrum replacers.

  20. Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.

    Read, Thomas; Olkhov, Rouslan V; Williamson, E Diane; Shaw, Andrew M


    A unified approach to affinity screening for Fab and Fc interactions of an antibody for its antigen and FcγR receptor has been developed. An antigen array is used for the Fab affinity and cross-reactivity screening and protein A/G proxy is the FcγR receptor. The affinities are derived using a simple 1:1 binding model with a consistent error analysis. The association and dissociation kinetics are measured over optimised times for accurate determination. The Fab/Fc affinities are derived for ten antibodies: mAb-actin (mouse), pAb-BSA (sheep), pAb-collagen V (rabbit), pAb-CRP (goat), mAb-F1 (mouse), mAbs (mouse) 7.3, 12.3, 29.3, 36.3 and 46.3 raised against LcrV in Yersinia pestis. The rate of the dissociation of antigen-antibody complexes relates directly to their immunological function as does the Fc-FcγR complex and a new half-life plot has been defined with a Fab/Fc half-life range of 17-470 min. The upper half-life value points to surface avidity. Two antibodies that are protective as an immunotherapy define a Fab half-life >250 min and an Fc half-life >50 min as characteristics of ideal interactions which can form the basis of an antibody screen for immunotherapy.

  1. Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

    Glen Daniel


    -lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve. Conclusion Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature.

  2. Perfluorooctane Sulfonate Plasma Half-Life Determination and Long-Term Tissue Distribution in Beef Cattle (Bos taurus).

    Lupton, Sara J; Dearfield, Kerry L; Johnston, John J; Wagner, Sarah; Huwe, Janice K


    Perfluorooctane sulfonate (PFOS) is used in consumer products as a surfactant and is found in industrial and consumer waste, which ends up in wastewater treatment plants (WWTPs). PFOS does not breakdown during WWTP processes and accumulates in the biosolids. Common practices include application of biosolids to pastures and croplands used for feed, and as a result, animals such as beef cattle are exposed to PFOS. To determine plasma and tissue depletion kinetics in cattle, 2 steers and 4 heifers were dosed with PFOS at 0.098 mg/kg body weight and 9.1 mg/kg, respectively. Plasma depletion half-lives for steers and heifers were 120 ± 4.1 and 106 ± 23.1 days, respectively. Specific tissue depletion half-lives ranged from 36 to 385 days for intraperitoneal fat, back fat, muscle, liver, bone, and kidney. These data indicate that PFOS in beef cattle has a sufficiently long depletion half-life to permit accumulation in edible tissues.

  3. Degradation and half-life of DNA present in biomass from a genetically-modified organism during land application.

    Halter, Mathew C; Zahn, James A


    White biotechnology has made a positive impact on the chemical industry by providing safer, more efficient chemical manufacturing processes that have reduced the use of toxic chemicals, harsh reaction conditions, and expensive metal catalysts, which has improved alignment with the principles of Green Chemistry. The genetically-modified (GM) biocatalysts that are utilized in these processes are typically separated from high-value products and then recycled, or eliminated. Elimination routes include disposal in sanitary landfills, incineration, use as a fuel, animal feed, or reuse as an agricultural soil amendment or other value-added products. Elimination routes that have the potential to impact the food chain or environment have been more heavily scrutinized for the fate and persistence of biological products. In this study, we developed and optimized a method for monitoring the degradation of strain-specific DNA markers from a genetically-modified organism (GMO) used for the commercial production of 1,3-propanediol. Laboratory and field tests showed that a marker for heterologous DNA in the GM organism was no longer detectable by end-point polymerase chain reaction (PCR) after 14 days. The half-life of heterologous DNA was increased by 17% (from 42.4 to 49.7 h) after sterilization of the soil from a field plot, which indicated that abiotic factors were important in degradation of DNA under field conditions. There was no evidence for horizontal transfer of DNA target sequences from the GMO to viable organisms present in the soil.

  4. Plasma half-life and organ uptake ratio of radiolabeled glandular kallikrein in control and nephrectomized rats

    Nishimura, K.; Iwata, T.; Kokubu, T.


    The purified rat urinary kallikrein was radiolabeled by lactoperoxidase method and by chloramine T method. Plasma half-life of radiolabeled kallikrein was 5.06 +/- 0.59 (n = 5) min in control rats and 5.24 +/- 0.42 (n = 5) min in nephrectomized rats. There was no difference between two groups. From autoradiogram, main metabolic organs of radiolabeled kallikrein were liver, kidney and spleen. Total uptake of radiolabeled kallikrein in ech organ was the highest in liver (73.2%). The uptake per g tissue of radiolabeled kallikrein in each organ was high in liver (33.0%), kidney (31.4%) and spleen (21.1%). These results suggest that the active kallikrein is metabolized mainly in the liver, and kidney is not so an important organ to metabolize or to eliminate the active kallikrein in plasma. In order to clarify the mode of existence of active kallikrein in plasma, the following experiment was done by using disc gel electrophoresis. Radioactive profile of radiolabeled kallikrein showed one peak (Rf = 1.0), but radiolabeled kallikrein mixed with rat plasma showed two peaks, that is small peak (Rf = 1.0), and main peak (RF = 0.5). The most of radiolabeled kallikrein was bound to plasma protein and only five per cent was in free form. Furthermore, the binding of radiolabeled kallikrein to plasma protein was interfered by the addition of active kallikrein. These results suggest the possibility of existence of kallikrein binding protein in plasma.

  5. Use of short half-life cosmogenic isotopes to quantify sediment mixing and transport in karst conduits

    Paylor, R.


    Particulate inorganic carbon (PIC) transport and flux in karst aquifers is poorly understood. Methods to quantify PIC flux are needed in order to account for total inorganic carbon removal (chemical plus mechanical) from karst settings. Quantifying PIC flux will allow more accurate calculations of landscape denudation and global carbon sink processes. The study concentrates on the critical processes of the suspended sediment component of mass flux - surface soil/stored sediment mixing, transport rates and distance, and sediment storage times. The primary objective of the study is to describe transport and mixing with the resolution of single storm-flow events. To quantify the transport processes, short half-life cosmogenic isotopes are utilized. The isotopes 7Be (t1/2 = 53d) and 210Pb (t1/2 = 22y) are the primary isotopes measured, and other potential isotopes such as 137Cs and 241Am are investigated. The study location is at Mammoth Cave National Park within the Logsdon River watershed. The Logsdon River conduit is continuously traversable underground for two kilometers. Background levels and input concentrations of isotopes are determined from soil samples taken at random locations in the catchment area, and suspended sediment collected from the primary sinking stream during a storm event. Suspended sediment was also collected from the downstream end of the conduit during the storm event. After the storm flow receded, fine sediment samples were taken from the cave stream at regular intervals to determine transport distances and mixing ratios along the conduit. Samples were analyzed with a Canberra Industries gamma ray spectrometer, counted for 24 hours to increase detection of low radionuclide activities. The measured activity levels of radionuclides in the samples were adjusted for decay from time of sampling using standard decay curves. The results of the study show that surface sediment mixing, transport and storage in karst conduits is a dynamic but

  6. Half-life of Re184 populated by the (γ,n) reaction from laser Compton scattering γ rays at the electron storage ring NewSUBARU

    Hayakawa, T.; Miyamoto, S.; Hayashi, Y.; Kawase, K.; Horikawa, K.; Chiba, S.; Nakanishi, K.; Hashimoto, H.; Ohta, T.; Kando, M.; Mochizuki, T.; Kajino, T.; Fujiwara, M.


    We report a half-life of the ground state of Re184 populated by the Re185(γ,n)Re184 reaction from laser Compton scattering γ rays generated through relativistic engineering. The γ rays are provided at the electron storage ring NewSUBARU. The previous experiment using deuteron-induced reactions has yielded a recommended half-life of the 3- ground state of Re184 of 38.0±0.5 d, including a possible contribution from the 8+ isomer (T1/2=169±8 d) of Re184 since the presence of the isomer was not known at that time. In contrast, the (γ,n) reaction has an advantage to selectively populate the ground state because this reaction does not bring large angular momentum. The measured half-life of 35.4±0.7 d is shorter than the previous half-life by about 7%. This difference is crucial for applications using the activation method.

  7. Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells.

    Sharova, Lioudmila V; Sharov, Alexei A; Nedorezov, Timur; Piao, Yulan; Shaik, Nabeebi; Ko, Minoru S H


    Degradation of mRNA is one of the key processes that control the steady-state level of gene expression. However, the rate of mRNA decay for the majority of genes is not known. We successfully obtained the rate of mRNA decay for 19 977 non-redundant genes by microarray analysis of RNA samples obtained from mouse embryonic stem (ES) cells. Median estimated half-life was 7.1 h and only genes, including Prdm1, Myc, Gadd45 g, Foxa2, Hes5 and Trib1, showed half-life less than 1 h. In general, mRNA species with short half-life were enriched among genes with regulatory functions (transcription factors), whereas mRNA species with long half-life were enriched among genes related to metabolism and structure (extracellular matrix, cytoskeleton). The stability of mRNAs correlated more significantly with the structural features of genes than the function of genes: mRNA stability showed the most significant positive correlation with the number of exon junctions per open reading frame length, and negative correlation with the presence of PUF-binding motifs and AU-rich elements in 3'-untranslated region (UTR) and CpG di-nucleotides in the 5'-UTR. The mRNA decay rates presented in this report are the largest data set for mammals and the first for ES cells.

  8. Database for mRNA Half-Life of 19 977 Genes Obtained by DNA Microarray Analysis of Pluripotent and Differentiating Mouse Embryonic Stem Cells

    Sharova, Lioudmila V.; Sharov, Alexei A.; Nedorezov, Timur; Piao, Yulan; Shaik, Nabeebi; Ko, Minoru S.H.


    Degradation of mRNA is one of the key processes that control the steady-state level of gene expression. However, the rate of mRNA decay for the majority of genes is not known. We successfully obtained the rate of mRNA decay for 19 977 non-redundant genes by microarray analysis of RNA samples obtained from mouse embryonic stem (ES) cells. Median estimated half-life was 7.1 h and only <100 genes, including Prdm1, Myc, Gadd45 g, Foxa2, Hes5 and Trib1, showed half-life less than 1 h. In general, mRNA species with short half-life were enriched among genes with regulatory functions (transcription factors), whereas mRNA species with long half-life were enriched among genes related to metabolism and structure (extracellular matrix, cytoskeleton). The stability of mRNAs correlated more significantly with the structural features of genes than the function of genes: mRNA stability showed the most significant positive correlation with the number of exon junctions per open reading frame length, and negative correlation with the presence of PUF-binding motifs and AU-rich elements in 3′-untranslated region (UTR) and CpG di-nucleotides in the 5′-UTR. The mRNA decay rates presented in this report are the largest data set for mammals and the first for ES cells. PMID:19001483

  9. Platelet half-life in patients with primary hyperlipoproteinemia type IIa, IIb, and IV according to Fredrickson with and without clinical signs of atherosclerosis

    Jaeger, E.; Sinzinger, H.; Widhalm, K.; Kaliman, J.; Hoefer, R. (Vienna Univ. (Austria). 2. Medizinische Klinik; Ludwig Boltzmann-Institut fuer Nuklearmedizin, Vienna (Austria); Vienna Univ. (Austria). Kinderklinik; Vienna Univ. (Austria). Kardiologische Klinik)


    It is generally accepted that platelet half-life is shortened in atherosclerotic vascular diseases. Concerning changes due to hyperlipoproteinemia (HLP), however, there exist only few data. Therefore, we examined the platelet-half life in 60 patients with recently discovered HLP type IIa, IIb and IV according to Fredrickson before treatment in comparison to 60 controls. 33 of the HLP-patients had no clinical symptoms of angiopathy. 27 patients suffered from peripheral vascular disease or from coronary heart disease as verified by angiography. The labelling of autologous platelets was performed with of /sup 111/Indium-oxine-sulfate at 37/sup 0/C for 5 minutes. The mean labelling efficiency was 90%, the recovery after 2 hours about 70%. Serum lipoproteins were estimated by means of ultracentrifugation and polyanionprecipitation according to Lipid Research Clinic Methods. In the patients with HLP platelet half-life was significantly shortened in comparison to the control group (p < 0.01). These changes were most pronounced in patients with HLP-type IIa and with atherosclerotic lesions, respectively. In patients with HLP-type IIa a very close correlation could be demonstrated between platelet half-life and LDL-cholesterol (r = -0.72; p < 0.001) as well as total cholesterol (r = -0.73; p < 0.001). These data prove that in HLP in-vivo platelet function as measured by platelet survival is significantly influenced even before the occurrence of clinically relevant symptoms of atherosclerosis.

  10. First measurements on how pressure affects the half-life of 22Na: Comparison to theory and analog to 40K

    Lee, K. K.; Nelson, R. O.; Rundberg, R.; Steinle-Neumann, G.


    Radioactive decay plays a central role in planetary sciences as appropriate decay schemes are used to date geological and astronomical processes and radioactivity provides an important source of heat in planetary bodies, both in their early history during accretion and differentiation and also over geological times. The most important isotopes that currently heat the Earth are 40K, 232Th, 235U and 238U. As radioactive decay is a nuclear process it is considered to be insensitive to external factors such as pressure or chemical environment. This has been shown to be true for α, β+ and β- processes, however, electron capture decay is dependent on the electron charge density at the nucleus of a compound, which is sensitive to the external environment. Using high-resolution Ge gamma-ray detectors to make relative measurements with 137Cs and the positron decay of 22Na, we measure how pressure affects the half-life of 22Na due to electron-capture decay. Our systematics look favorable for observing this small effect. We will compare our preliminary measurements with complementary ab-initio all-electron computations using the linearized augmented plane wave method (LAPW). Using 22Na as an analog for 40K, our results suggest that the pressure effect for 40K, combined with the opposing effects of high temperatures, will have little, discernible effect on the heat production in the deep Earth as our predicted changes are smaller than the uncertainties in the total decay constant for 40K. This work was supported in part by the Carnegie/DOE Alliance Center (CDAC), through the Stewardship Science Academic Alliances Program of the U.S. Department of Energy. The LANSCE facility is operated, and portions of this work were performed, by Los Alamos National Security, LLC, funded by the U.S. Department of Energy under Contract No. DE-AC52- 06NA25396.

  11. 基于下载量的期刊半衰期实证研究%Empirical Research on Half-life Period of Journals Based on Downloads



    针对期刊网络老化速度研究较为薄弱的状况,以CNKI为数据源,通过对图书馆学情报学期刊下载量半衰期的实证分析研究,解读了下载量半衰期的特点,剖析了其与其它期刊评价指标的区别与联系。结果显示:期刊下载量半衰期明显小于被引半衰期和引用半衰期,与被引半衰期之间存在显著的相关性;与期刊其它计量指标相比有其特质与独立性;开展期刊下载量半衰期研究,有利于突破老化研究中引文分析的藩篱,提升期刊评价的时效性,拓展考察范围及促进期刊出版机构主动缩短网络版与印刷版之间的出版时滞,对期刊整体影响力的提升将产生积极影响。%Aimed at the unsubstantial research on aging speed of network periodicals and taking CNKI as data source, the paper interprets the characteristics of half-life period of downloads, and analyses its differences and relations with other periodical evaluation indexes through the empirical analysis research on half-life period of downloads as to library &information science periodicals. The result shows that half-life period of journal downloads are much smaller than cited half-life period and citation half-life period, and there is significant correlation with the cited half-life period among them as well;but compared with other periodical evaluation indexes, there exist its own traits and independence; it avails for the research of half-life periodical downloads to break through barriers in the study of aging citation analysis, to improve the timeliness of periodical evaluation and expand the scope of inspection, and also to promote periodical publishing organizations to take the initiative shortening of the delay between online and print publication, which will have a positive impact on the promotion of overall journal influence.

  12. Fast renal trapping of porcine Luteinizing Hormone (pLH shown by 123I-scintigraphic imaging in rats explains its short circulatory half-life

    Locatelli Alain


    Full Text Available Abstract Background Sugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and consequently their in vivo biopotencies. In order to relate more precisely hepatic trapping of these glycoproteic hormones with their circulatory half-life, we undertook a comparative study of the distribution and elimination of porcine LH (pLH and equine CG (eCG which exhibit respectively a short and a long half-life. This was done first by following half-lives of pLH in piglets with hepatic portal circulation shunted or not. It was expected that such a shunt would enhance the short half-life of pLH. Subsequently, scintigraphic imaging of both 123I-pLH and 123I-eCG was performed in intact rats to compare their routes and rates of distribution and elimination. Methods Native pLH or eCG was injected to normal piglets and pLH was tested in liver-shunted anæsthetized piglet. Blood samples were recovered sequentially over one hour time and the hormone concentrations were determined by a specific ELISA method. Scintigraphic imaging of 123I-pLH and 123I-eCG was performed in rats using a OPTI-CGR gamma camera. Results In liver-shunted piglets, the half-life of pLH was found to be as short as in intact piglets (5 min. In the rat, the half-life of pLH was also found to be very short (3–6 min and 123I-pLH was found to accumulate in high quantity in less than 10 min post injection at the level of kidneys but not in the liver. 123I-eCG didn't accumulate in any organ in the rats during the first hour, plasma concentrations of this gonadotropin being still elevated (80% at this time. Conclusion In both the porcine and rat species, the liver is not responsible for the rapid elimination of pLH from the circulation compared to eCG. Our scintigraphic experiments suggest that the very short circulatory half-life of LH is due to rapid renal trapping.

  13. Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis


    BACKGROUND: Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage.OBJECTIVE: To observe therapeutic effect of modified subhibernation therapy (alterative application of five anticonvulsants according to the half life) on status epilepticus in children with severe viral encephalitis (VE).DESIGN: Contrast observation.SETTING: Department of Pediatrics, the First Hospital of Jilin University.PARTICIPANTS: The participants in present study were 96 patients withsevere viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics (the seventh edition). Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion,nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography (EEG)abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group (n =40) and experimental group (n =56).METHODS: Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs: 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride (0.5 mL/kg), 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked,those five drugs were given alternatively; however, those were not given if the convulsion did not attack.Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the

  14. A new value for the half-life of {sup 10}Be by Heavy-Ion Elastic Recoil Detection and liquid scintillation counting

    Korschinek, G., E-mail: Gunther.Korschinek@ph.tum.d [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Bergmaier, A. [Universitaet der Bundeswehr Muenchen, Fakultaet fuer Luft- und Raumfahrttechnik, Institut fuer Angewandte Physik und Messtechnik LRT2, Werner-Heisenberg-Weg 39, D-85577 Neubiberg (Germany); Faestermann, T. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Gerstmann, U.C. [Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Radiation Protection, Ingolstaedter Landstr. 1, D-85764 Neuherberg (Germany); Knie, K.; Rugel, G. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Wallner, A. [VERA Laboratory, Faculty of Physics, University of Vienna, Waehringer Strasse 17, A-1090 Wien (Austria); Dillmann, I. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Dollinger, G. [Universitaet der Bundeswehr Muenchen, Fakultaet fuer Luft- und Raumfahrttechnik, Institut fuer Angewandte Physik und Messtechnik LRT2, Werner-Heisenberg-Weg 39, D-85577 Neubiberg (Germany); Lierse von Gostomski, Ch. [Lehrstuhl fuer Radiochemie, Technische Universitaet Muenchen, D-85748 Garching (Germany); Kossert, K. [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany); Maiti, M.; Poutivtsev, M. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Remmert, A. [Lehrstuhl fuer Radiochemie, Technische Universitaet Muenchen, D-85748 Garching (Germany)


    The importance of {sup 10}Be in different applications of accelerator mass spectrometry (AMS) is well-known. In this context the half-life of {sup 10}Be has a crucial impact, and an accurate and precise determination of the half-life is a prerequisite for many of the applications of {sup 10}Be in cosmic-ray and earth science research. Recently, the value of the {sup 10}Be half-life has been the centre of much debate. In order to overcome uncertainties inherent in previous determinations, we introduced a new method of high accuracy and precision. An aliquot of our highly enriched {sup 10}Be master solution was serially diluted with increasing well-known masses of {sup 9}Be. We then determined the initial {sup 10}Be concentration by least square fit to the series of measurements of the resultant {sup 10}Be/{sup 9}Be ratio. In order to minimize uncertainties because of mass bias which plague other low-energy mass spectrometric methods, we used for the first time Heavy-Ion Elastic Recoil Detection (HI-ERD) for the determination of the {sup 10}Be/{sup 9}Be isotopic ratios, a technique which does not suffer from difficult to control mass fractionation. The specific activity of the master solution was measured by means of accurate liquid scintillation counting (LSC). The resultant combination of the {sup 10}Be concentration and activity yields a {sup 10}Be half-life of T{sub 1/2} = 1.388 +- 0.018 (1 s, 1.30%) Ma. In a parallel but independent study (Chmeleff et al. ), found a value of 1.386 +- 0.016 (1.15%) Ma. Our recommended weighted mean and mean standard error for the new value for {sup 10}Be half-life based on these two independent measurements is 1.387 +- 0.012 (0.87%) Ma.

  15. Refinements on the age-dependent half-life model for estimating child body burdens of polychlorodibenzodioxins and dibenzofurans.

    Kerger, Brent D; Leung, Hon-Wing; Scott, Paul K; Paustenbach, Dennis J


    We modified our prior age-dependent half-life model to characterize the range of child (ages 0-7) body burdens associated with dietary and environmental exposure to polychlorodibenzodioxins and furans (PCDD/Fs). Several exposure scenarios were evaluated. Infants were assumed to be either breast-fed or formula-fed from birth to 6 months of age. They then received intakes of PCDD/Fs through age 7 from foods based on weighted means estimates [JECFA, 2001. Joint FAO/WHO Committee on Food Additives. Fifty-seventh meeting, Rome, June 5-14 , 2001, pp. 24-40], and with or without exposures (ingestion and dermal) to urban residential soils at 1ppb TCDD toxic equivalents (TEQ). A one-compartment (adipose volume) toxicokinetic model for TCDD described by Kreuzer [Kreuzer, P.F., Csanady, Gy.A., et al., 1997. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch. Toxicol. 71, 383-400] was expanded to include the key non-TCDD congeners in human breast milk and adipose tissues, and two model parameter refinements were examined: (1) use of updated and more detailed age-correlated body fat mass data [CDC, 2000. Centers for Disease Control. CDC Growth Charts: United States. Advance Data from Vital and Health Statistics of the Centers for Disease Control and Prevention, National Center for Health Statistics, Number 314, December 2000]; (2) use of breast milk PCDD/F concentration data from sampling completed in 2000-2003 [Wittsiepe, J., Fürst, P., et al., 2004. PCDD/F and dioxin-like PCB in human blood and milk from German mothers. Organohalogen Compd. 66, 2865-2872]. The updated body fat mass data nearly halved the predicted peak body burden for breast-feeding and lowered the time-weighted average (TWA) body burdens from ages 0-7 by 30-40% for breast-fed and formula-fed infants. Combined use of the updated breast milk PCDD/F concentration and body fat

  16. Measurement of the two-neutrino double-beta decay half-life of {sup 130}Te with the CUORE-0 experiment

    Alduino, C.; Avignone, F.T.; Chott, N.; Creswick, R.J.; Rosenfeld, C.; Wilson, J. [University of South Carolina, Department of Physics and Astronomy, Columbia, SC (United States); Alfonso, K.; Hickerson, K.P.; Huang, H.Z.; Liu, X.; Trentalange, S.; Zhu, B.X. [University of California, Department of Physics and Astronomy, Los Angeles, CA (United States); Artusa, D.R. [University of South Carolina, Department of Physics and Astronomy, Columbia, SC (United States); INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Azzolini, O.; Camacho, A.; Keppel, G.; Palmieri, V.; Pira, C. [INFN-Laboratori Nazionali di Legnaro, Legnaro, Padova (Italy); Banks, T.I.; Drobizhev, A.; Freedman, S.J.; Hennings-Yeomans, R.; O' Donnell, T.; Wagaarachchi, S.L. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Bari, G.; Deninno, M.M. [INFN-Sezione di Bologna, Bologna (Italy); Beeman, J.W. [Lawrence Berkeley National Laboratory, Materials Science Division, Berkeley, CA (United States); Bellini, F.; Cardani, L.; Casali, N.; Cosmelli, C.; Ferroni, F. [Sapienza Universita di Roma, Dipartimento di Fisica, Rome (Italy); INFN-Sezione di Roma, Rome (Italy); Bersani, A.; Caminata, A. [INFN-Sezione di Genova, Genova (Italy); Biassoni, M.; Carbone, L.; Cremonesi, O.; Ferri, E.; Giachero, A.; Pessina, G.; Previtali, E.; Rusconi, C. [INFN-Sezione di Milano Bicocca, Milan (Italy); Brofferio, C.; Capelli, S.; Carniti, P.; Cassina, L.; Chiesa, D.; Clemenza, M.; Faverzani, M.; Fiorini, E.; Gironi, L.; Gotti, C.; Maino, M.; Nucciotti, A.; Pavan, M.; Pozzi, S.; Sisti, M.; Terranova, F.; Zanotti, L. [Universita di Milano-Bicocca, Dipartimento di Fisica, Milan (Italy); INFN-Sezione di Milano Bicocca, Milan (Italy); Bucci, C.; Cappelli, L.; D' Addabbo, A.; Di Vacri, M.L.; Gorla, P.; Pattavina, L.; Pirro, S. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Canonica, L. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Massachusetts Institute of Technology, Cambridge, MA (United States); Cao, X.G.; Fang, D.Q.; Ma, Y.G.; Wang, H.W.; Zhang, G.Q. [Chinese Academy of Sciences, Shanghai Institute of Applied Physics, Shanghai (China); Copello, S.; Di Domizio, S.; Fernandes, G.; Marini, L.; Pallavicini, M. [INFN-Sezione di Genova, Genova (Italy); Universita di Genova, Dipartimento di Fisica, Genova (Italy); Cushman, J.S.; Davis, C.J.; Heeger, K.M.; Lim, K.E.; Maruyama, R.H. [Yale University, Department of Physics, New Haven, CT (United States); Dafinei, I.; Morganti, S.; Mosteiro, P.J.; Orio, F.; Pettinacci, V.; Tomei, C.; Vignati, M. [INFN-Sezione di Roma, Rome (Italy); Dell' Oro, S. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); INFN-Gran Sasso Science Institute, L' Aquila (Italy); Feintzeig, J.; Fujikawa, B.K.; Mei, Y.; Smith, A.R. [Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Franceschi, M.A.; Ligi, C.; Napolitano, T.; Piperno, G. [INFN-Laboratori Nazionali di Frascati, Frascati, Rome (Italy); Giuliani, A.; Tenconi, M. [Universite Paris-Saclay, CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Orsay (France); Gladstone, L.; Leder, A.; Winslow, L.A. [Massachusetts Institute of Technology, Cambridge, MA (United States); Gutierrez, T.D. [California Polytechnic State University, Physics Department, San Luis Obispo, CA (United States); Haller, E.E. [Lawrence Berkeley National Laboratory, Materials Science Division, Berkeley, CA (United States); University of California, Department of Materials Science and Engineering, Berkeley, CA (United States); Han, K. [Yale University, Department of Physics, New Haven, CT (United States); Shanghai Jiao Tong University, Department of Physics and Astronomy, Shanghai (China); Hansen, E. [University of California, Department of Physics and Astronomy, Los Angeles, CA (United States); Massachusetts Institute of Technology, Cambridge, MA (United States); Kadel, R. [Lawrence Berkeley National Laboratory, Physics Division, Berkeley, CA (United States); Kolomensky, Yu.G. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Physics Division, Berkeley, CA (United States); Martinez, M. [Sapienza Universita di Roma, Dipartimento di Fisica, Rome (Italy); INFN-Sezione di Roma, Rome (Italy); Universidad de Zaragoza, Laboratorio de Fisica Nuclear y Astroparticulas, Zaragoza (Spain); Moggi, N. [INFN-Sezione di Bologna, Bologna (Italy); Alma Mater Studiorum-Universita di Bologna, Dipartimento di Scienze per la Qualita della Vita, Bologna (Italy); Nones, C. [Service de Physique des Particules, CEA/Saclay, Gif-sur-Yvette (France); Norman, E.B.; Wang, B.S. [Lawrence Livermore National Laboratory, Livermore, CA (United States); University of California, Department of Nuclear Engineering, Berkeley, CA (United States); Ouellet, J.L. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Massachusetts Institute of Technology, Cambridge, MA (United States); Pagliarone, C.E. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Universita degli Studi di Cassino e del Lazio Meridionale, Dipartimento di Ingegneria Civile e Meccanica, Cassino (Italy); Sangiorgio, S.; Scielzo, N.D. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Santone, D. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Universita dell' Aquila, Dipartimento di Scienze Fisiche e Chimiche, L' Aquila (Italy); Singh, V. [University of California, Department of Physics, Berkeley, CA (US); Taffarello, L. [INFN-Sezione di Padova, Padova (IT); Wise, T. [Yale University, Department of Physics, New Haven, CT (US); University of Wisconsin, Department of Physics, Madison, WI (US); Woodcraft, A. [University of Edinburgh, SUPA, Institute for Astronomy, Edinburgh (GB); Zimmermann, S. [Lawrence Berkeley National Laboratory, Engineering Division, Berkeley, CA (US); Zucchelli, S. [INFN-Sezione di Bologna, Bologna (IT); Alma Mater Studiorum-Universita di Bologna, Dipartimento di Fisica e Astronomia, Bologna (IT)


    We report on the measurement of the two-neutrino double-beta decay half-life of {sup 130}Te with the CUORE-0 detector. From an exposure of 33.4 kg year of TeO{sub 2}, the half-life is determined to be T{sub 1/2}{sup 2ν} = [8.2 ± 0.2 (stat.) ± 0.6 (syst.)] x 10{sup 20} year. This result is obtained after a detailed reconstruction of the sources responsible for the CUORE-0 counting rate, with a specific study of those contributing to the {sup 130}Te neutrinoless double-beta decay region of interest. (orig.)

  17. Measurement of the half-life of the two-neutrino double beta decay of Ge-76 with the Gerda experiment

    Agostini, M; Andreotti, E; Bakalyarov, A M; Balata, M; Barabanov, I; Heider, M Barnabe; Barros, N; Baudis, L; Bauer, C; Becerici-Schmidt, N; Bellotti, E; Belogurov, S; Belyaev, S T; Benato, G; Bettini, A; Bezrukov, L; Bode, T; Brudanin, V; Brugnera, R; Budjas, D; Caldwell, A; Cattadori, C; Chernogorov, A; Cossavella, F; Demidova, E V; Denisov, A; Domula, A; Egorov, V; Falkenstein, R; Ferella, A D; Freund, K; Froborg, F; Frodyma, N; Gangapshev, A; Garfagnini, A; Gazzana, S; Grambayr, P; Gurentsov, V; Gusev, K; Guthikonda, K K; Hampel, W; Hegai, A; Heisel, M; Hemmer, S; Heusser, G; Hofmann, W; Hult, M; Inzhechik, L V; Ioannucci, L; Csathy, J Janicsko; Jochum, J; Junker, M; Kianovsky, S; Kirpichnikov, I V; Kirsch, A; Klimenko, A; Knoepfle, K T; Kochetov, O; Kornoukhov, V N; Kusminov, V; Laubenstein, M; Lazzaro, A; Lebedev, V I; Lehnert, B; Liao, H Y; Lindner, M; Lippi, I; Liu, X; Lubashevskiy, A; Lubsandorzhiev, B; Lutter, G; Machado, A A; Majorovits, B; Maneschg, W; Nemchenok, I; Nisi, S; O'Shaughnessy, C; Pandola, L; Pelczar, K; Peraro, L; Pullia, A; Riboldi, S; Ritter, F; Sada, C; Salathe, M; Schmitt, C; Schoenert, S; Schreiner, J; Schulz, O; Schwingenheuer, B; Shevchik, E; Shirchenko, M; Simgen, H; Smolnikov, A; Stanco, L; Strecker, H; Tarka, M; Ur, C A; Vasenko, A A; Volynets, O; von Sturm, K; Walter, M; Wegmann, A; Wojcik, M; Yanovich, E; Zavarise, P; Zhitnikov, I; Zhukov, S V; Zinatulina, D; Zuber, K; Zuzel, G


    The primary goal of the GERmanium Detector Array (Gerda) experiment at the Laboratori Nazionali del Gran Sasso of INFN is the search for the neutrinoless double beta decay of Ge-76. High-purity germanium detectors made from material enriched in Ge-76 are operated directly immersed in liquid argon, allowing for a substantial reduction of the background with respect to predecessor experiments. The first 5.04 kg yr of data collected in Phase I of the experiment have been analyzed to measure the half-life of the neutrino-accompanied double beta decay of Ge-76. The observed spectrum in the energy range between 600 and 1800 keV is dominated by the double beta decay of Ge-76. The half-life extracted from Gerda data is T(1/2) = (1.84 +0.14 -0.10) 10^{21} yr.

  18. Measurement of the two-neutrino double-beta decay half-life of $^{130}$ Te with the CUORE-0 experiment

    Alduino, C.; Alfonso, K.; Artusa, D. R.; Avignone, F. T.; Azzolini, O.; Banks, T. I.; Bari, G.; Beeman, J. W.; Bellini, F.; Bersani, A.; Biassoni, M.; Brofferio, C.; Bucci, C.; Camacho, A.; Caminata, A.; Canonica, L.; Cao, X. G.; Capelli, S.; Cappelli, L.; Carbone, L.; Cardani, L.; Carniti, P.; Casali, N.; Cassina, L.; Chiesa, D.; Chott, N.; Clemenza, M.; Copello, S.; Cosmelli, C.; Cremonesi, O.; Creswick, R. J.; Cushman, J. S.; D’Addabbo, A.; Dafinei, I.; Davis, C. J.; Dell’Oro, S.; Deninno, M. M.; Di Domizio, S.; Di Vacri, M. L.; Drobizhev, A.; Fang, D. Q.; Faverzani, M.; Feintzeig, J.; Fernandes, G.; Ferri, E.; Ferroni, F.; Fiorini, E.; Franceschi, M. A.; Freedman, S. J.; Fujikawa, B. K.; Giachero, A.; Gironi, L.; Giuliani, A.; Gladstone, L.; Gorla, P.; Gotti, C.; Gutierrez, T. D.; Haller, E. E.; Han, K.; Hansen, E.; Heeger, K. M.; Hennings-Yeomans, R.; Hickerson, K. P.; Huang, H. Z.; Kadel, R.; Keppel, G.; Kolomensky, Yu. G.; Leder, A.; Ligi, C.; Lim, K. E.; Liu, X.; Ma, Y. G.; Maino, M.; Marini, L.; Martinez, M.; Maruyama, R. H.; Mei, Y.; Moggi, N.; Morganti, S.; Mosteiro, P. J.; Napolitano, T.; Nones, C.; Norman, E. B.; Nucciotti, A.; O’Donnell, T.; Orio, F.; Ouellet, J. L.; Pagliarone, C. E.; Pallavicini, M.; Palmieri, V.; Pattavina, L.; Pavan, M.; Pessina, G.; Pettinacci, V.; Piperno, G.; Pira, C.; Pirro, S.; Pozzi, S.; Previtali, E.; Rosenfeld, C.; Rusconi, C.; Sangiorgio, S.; Santone, D.; Scielzo, N. D.; Singh, V.; Sisti, M.; Smith, A. R.; Taffarello, L.; Tenconi, M.; Terranova, F.; Tomei, C.; Trentalange, S.; Vignati, M.; Wagaarachchi, S. L.; Wang, B. S.; Wang, H. W.; Wilson, J.; Winslow, L. A.; Wise, T.; Woodcraft, A.; Zanotti, L.; Zhang, G. Q.; Zhu, B. X.; Zimmermann, S.; Zucchelli, S.


    We report on the measurement of the two-neutrino double-beta decay half-life of 130 Te with the CUORE-0 detector. From an exposure of 33.4 kg year of TeO 22 , the half-life is determined to be T$2ν\\atop{1/2}$ = [8.2 ± 0.2 (stat.) ± 0.6 (syst.)] ×× 10 20 year. This result is obtained after a detailed reconstruction of the sources responsible for the CUORE-0 counting rate, with a specific study of those contributing to the 130130 Te neutrinoless double-beta decay region of interest.

  19. Nicotinic stimulation modulates tyrosine hydroxylase mRNA half-life and protein binding to the 3'UTR in a manner that requires transcription.

    Roe, David F; Craviso, Gale L; Waymire, Jack C


    Tyrosine hydroxylase (TH) expression increases in adrenal chromaffin cells treated with the nicotinic agonist, dimethylphenylpiperazinium (DMPP; 1 microM). We are using this response as a model of the changes in TH level that occur during increased cholinergic neural activity. Here we report a 4-fold increase in TH mRNA half-life in DMPP-treated cells chromaffin cells that is apparent when using a pulse-chase analysis to measure TH mRNA half-life. No increase is apparent using actinomycin D to measure half-life, indicating a requirement for ongoing transcription. Characterization of protein binding to the TH 3'UTR responsible for stabilization using labeled TH 3'UTR probes and electro-mobility shift assays shows the presence of two complexes both of which are increased by DMPP-treatment. The faster migrating complex (FMC) increases 2.5-fold and the slower migrating complex (SMC) increases 1.5-fold. Both changes are prevented by actinomycin D. Characterization of the protein binding to the TH UTR probes indicates SMC is disrupted by polyribonucleotides, poly (A) and poly (U), while binding to FMC is reduced by poly (CU). Separation of UV crosslinked RNA-protein complexes on SDS polyacrylamide gels shows FMC to contain a single protein whereas SMC contains three proteins. Northwesterns yielded similar results. Comparison of DMPP-induced protein binding with the poly C binding protein (PCBP) involved in hypoxia induced rat PC12 TH mRNA stability indicates none of the bovine UTR binding proteins are the PCBP. Thus, nicotinic stimulation produces a transcription-dependent increase in TH mRNA half-life that is mediated by previously unrecognized TH mRNA binding proteins.

  20. Biological half-life of radioactive cesium in Japanese rockfish Sebastes cheni contaminated by the Fukushima Daiichi nuclear power plant accident.

    Matsumoto, Akira; Shigeoka, Yu; Arakawa, Hisayuki; Hirakawa, Naoto; Morioka, Yoshiaki; Mizuno, Takuji


    Since the Fukushima accident in March 2011 the concentration of radioactive cesium in Japanese rockfish (Sebastes cheni) has been decreasing slower than other fish species. The aim of this study was therefore to investigate the possibility of slow elimination rate (i.e., relatively longer Tb) as one of the reasons for the slow decrease in (137)Cs concentrations in Japanese rockfish (S. cheni). To do this, we reared twenty-three individuals of this species for a period of about 1 year, during which time we measured the (137)Cs concentrations and γ-ray spectra 14 times by using a high-efficiency NaI(Tl) scintillator. We then examined the relationship between the (137)Cs concentrations and the total length of each individual. We estimated the biological half-life (Tb, day) for each individual using the total number of (137)Cs counts in the energy region, and examined the effects of total length and (137)Cs concentration on Tb by generalized linear model (GLM). We also examined the effect of sex, total length, seawater temperature, and the (137)Cs concentration of seawater on temporal changes in the (137)Cs count reduction rate by GLM. There was no clear relationship between the corrected whole-body (137)Cs concentrations and the total length in females, however there was a significant positive correlation between these two variables in males. The difference between males and females may be attributable to variation in the degree of dilution because of variable growth of individuals, and suggests that the (137)Cs concentrations of small individuals may be greatly diluted because of faster growth. However, there was no significant difference in Tb between sexes. The mean Tb (±SD) in all individuals was 269 (±39) days; this Tb value is 2.7-5.4 times longer than past Tb values (marine fish: 50-100 days), and is thought to be one of the reasons for the slower decrease in (137)Cs concentrations in this species than other fish species on the coast of Fukushima. The GLM


    S. A. Zhigalov


    Full Text Available Objective: to investigate the impact of the selectivity and half-life of nonsteroidal anti-inflammatory drugs (NSAIDs on the development of subclinical kidney injury (SKI. A standard physical examination was made.Patients and methods. The study included 80 patients with a verified rheumatoid arthritis (RA diagnosis. The patients filled in a specially designed questionnaire to explore a history of drug use. As markers of SKI, the investigators determined the concentrations of albumin, α1-microglobulin (α1-MG, alanine aminotransferase (ALT, and alkaline phosphatase (ALP in urine. A control group consisted of 20 apparently healthy individuals matched for age and gender.Results. 80 patients suffering from RA received drug therapy. Of them, 82.5% and 87.5% took NSAIDs and disease-modifying antirheumatic drugs, respectively. The levels of SKI markers were compared in three groups of the examinees: 1 NSAID-treated patients; 2 NSAID-untreated patients; 3 a control group. There were statistically significant differences between all the groups (p<0.05. Comparison of the levels of SKI markers revealed no statistically significant difference in the groups receiving selective cyclooxygenase-2 (COX-2 inhibitors (n=18.6%, in those taking nonselective ones (n=68.6%, and the control group. Comparison of the levels of SKI markers demonstrated significantly higher >< 0.05. Comparison of the levels of SKI markers revealed no statistically significant difference in the groups receiving selective cyclooxygenase-2 (COX-2 inhibitors (n=18.6%, in those taking nonselective ones (n=68.6%, and the control group. Comparison of the levels of SKI markers demonstrated significantly higher α1-MG levels in the long-acting NSAID groups (n=8.6% than in the short-acting NSAID group (n=80%. ALT, ALP, and microalbuminuria showed a similar trend that failed to reach statistical significance.Conclusion: NSAIDs remain a group of medications with a certain nephrotoxic effect. At the

  2. New limits on Beyond Standard Model physics from a measurement of the half-life of the T=1/2 mirror decay of 19Ne

    Broussard, L; Boswell, M S; Crowell, A S; Dendooven, P; Howell, C R; Kidd, M F; Jungmann, K; Kruithof, W L; Onderwater, C J G; Pattie, R W; Shidling, P D; Sohani, M; van der Hoek, D J; Rogachevskiy, A; Traykov, E; Versolato, O O; Willmann, L; Wilschut, H W; Young, A R


    The 1/2+ -> 1/2+ superallowed mixed mirror decay of 19Ne to 19F is excellently suited for high-precision studies of the weak interaction. However, there is some disagreement on the value of the half-life. In a new measurement we have determined this quantity to be T_{1/2} = 17.2832 +/- 0.0051_{(stat)} +/- 0.0066_{(sys)} seconds, which differs from the previous world average by 3 standard deviations. The impact of this measurement on limits for physics beyond the standard model such as the presence of tensor currents is discussed.

  3. Measurement of the Double-Beta Decay Half-Life and Search for the Neutrinoless Double-Beta Decay of $^{48}{\\rm Ca}$ with the NEMO-3 Detector

    :,; Augier, C; Bakalyarov, A M; Baker, J D; Barabash, A S; Basharina-Freshville, A; Blondel, S; Blot, S; Bongrand, M; Brudanin, V; Busto, J; Caffrey, A J; Calvez, S; Cascella, M; Cerna, C; Cesar, J P; Chapon, A; Chauveau, E; Chopra, A; Duchesneau, D; Durand, D; Egorov, V; Eurin, G; Evans, J J; Fajt, L; Filosofov, D; Flack, R; Garrido, X; Gómez, H; Guillon, B; Guzowski, P; Hodák, R; Huber, A; Hubert, P; Hugon, C; Jullian, S; Klimenko, A; Kochetov, O; Konovalov, S I; Kovalenko, V; Lalanne, D; Lang, K; Lebedev, V I; Lemière, Y; Noblet, T Le; Liptak, Z; Liu, X R; Loaiza, P; Lutter, G; Mamedov, F; Marquet, C; Mauger, F; Morgan, B; Mott, J; Nemchenok, I; Nomachi, M; Nova, F; Nowacki, F; Ohsumi, H; Pahlka, R B; Perrot, F; Piquemal, F; Povinec, P; Přidal, P; Ramachers, Y A; Remoto, A; Reyss, J L; Richards, B; Riddle, C L; Rukhadze, E; Rukhadze, N I; Saakyan, R; Salazar, R; Sarazin, X; Shitov, Yu; Simard, L; Šimkovic, F; Smetana, A; Smolek, K; Smolnikov, A; Söldner-Rembold, S; Soulé, B; Štekl, I; Suhonen, J; Sutton, C S; Szklarz, G; Thomas, J; Timkin, V; Torre, S; Tretyak, Vl I; Tretyak, V I; Umatov, V I; Vanushin, I; Vilela, C; Vorobel, V; Waters, D; Zhukov, S V; Žukauskas, A


    The NEMO-3 experiment at the Modane Underground Laboratory has investigated the double-$\\beta$ decay of $^{48}{\\rm Ca}$. Using $5.25$\\,yr of data recorded with a $6.99\\,{\\rm g}$ sample of $^{48}{\\rm Ca}$, approximately $150$ double-$\\beta$ decay candidate events have been selected with a signal-to-background ratio greater than $3$. The half-life for the two-neutrino double-$\\beta$ decay of $^{48}{\\rm Ca}$ has been measured to be \\mbox{$T^{2\

  4. 裂变产物94Y和95Y半衰期的测定%Half-life determination of fission products 94Y and95Y

    王世联; 白涛; 师全林; 张小林; 凡金龙; 李奇; 刘杰; 卢嘉春; 常永福


    用脉冲反应堆热中子辐照浓缩235U溶液靶,经快速放射化学分离纯化出94Y和95Y溶液,稀释并制备放射性浓度依次相差~10倍的3个测量源.将测量源放置在井式HPGe探测器井内,采用质量归一法测得94Y和95Y的半衰期分别为(19.16±0.05)min和(10.36±0.03)min.%Solutions of enriched235U were irradiated in thermal-neutron flux producedby apulsed reactor,and 94Yand 95Y werc separated chemically from the fission products immediately.The purified solution of 94Y and 95Y is diluted aboutten timgs in sequence to three concentration solutions.Three Sources were prepared with the solutions.The sources are measured,from the lower concentration to higher onc,with a well-type HPGe detector to determine the half-life of94Y and95Y.The determined half-life results arg(19.16±0.05)min and(10.35±0.04)min for94Y and 95Y respectively.

  5. Results of a search for daily and annual variations of the Po-214 half-life at the two year observation period

    Alexeyev, E N; Gangapshev, A M; Kazalov, V V; Kuzminov, V V; Panasenko, S I; Ratkevich, S S


    The brief description of installation TAU-2 intended for long-term monitoring of the half-life value $\\tau$ ($\\tau_{1/2}$) of the $^{214}$Po is presented. The methods of measurement and processing of collected data are reported. The results of analysis of time series values $\\tau$ with different time step are presented. Total of measurement time was equal to 590 days. Averaged value of the $^{214}$Po half-life was obtained $\\tau=163.46\\pm0.04$ $\\mu$s. The annual variation with an amplitude $A=(8.9\\pm2.3)\\cdot10^{-4}$, solar-daily variation with an amplitude $A_{So}=(7.5\\pm1.2)\\cdot10^{-4}$, lunar-daily variation with an amplitude $A_L=(6.9\\pm2.0)\\cdot10^{-4}$ and sidereal-daily variation with an amplitude $A_S=(7.2\\pm1.2)\\cdot10^{-4}$ were found in a series of $\\tau$ values. The maximal values of amplitude are observed at the moments when the projections of the installation Earth location velocity vectors toward the source of possible variation achieve its maximal magnitudes.

  6. Differential regulation of p21 (waf1) protein half-life by DNA damage and Nutlin-3 in p53 wild-type tumors and its therapeutic implications.

    Chang, Li-Ju; Eastman, Alan


    DNA damage induces the canonical p53 pathway including elevation of p21 (waf1) resulting in arrest of cell cycle progression. This can protect cells from subsequent Chk1 inhibition. Some p53 wild-type cancer cells such as HCT116 and U2OS exhibit attenuated p21 (waf1) induction upon DNA damage due to translational inhibition, and are incapable of maintaining arrest upon Chk1 inhibition. The purpose of this study was to determine whether this attenuated p21 (waf1) induction also occurred with the non-DNA damaging agent Nutlin-3 which induces p53 by disrupting binding to its negative regulator MDM2. We find that Nutlin-3 circumvented the attenuated induction of p21 (waf1) protein by increasing its half-life which led to G 1 and G 2 arrest in both cell lines. Interestingly, the p21 (waf1) protein half-life remained short on Nutlin-3 in p53 wild-type MCF10A cells; these cells achieve high p21 (waf1) levels through transcriptional upregulation. Consequently, all three p53 wild-type cells but not p53 mutant MDA-MB-231 cancer cells were protected from subsequent incubation with a combination of DNA damage plus a checkpoint inhibitor.

  7. Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA.

    Sawney, Sharad; Arora, Rashi; Aggarwal, Kamal K; Saluja, Daman


    One of the most frequent genetic aberrations in acute myeloid leukemia (AML) is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21) translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21) translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application.

  8. Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA

    Sharad Sawney


    Full Text Available One of the most frequent genetic aberrations in acute myeloid leukemia (AML is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21 translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21 translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application.

  9. New AMS method to measure the atom ratio {sup 146}Sm/{sup 147}Sm for a half-life determination of {sup 146}Sm

    Kinoshita, N. [Tandem Accelerator Complex, Research Facility Center for Science and Technology, University of Tsukuba (Japan); Paul, M., E-mail: [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel); Alcorta, M. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Bowers, M.; Collon, P. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556-5670 (United States); Deibel, C.M. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Joint Institute for Nuclear Astrophysics, Michigan State University, East Lansing, MI 46624 (United States); DiGiovine, B. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Goriely, S. [Universite Libre de Bruxelles, CP-226, Brussels 1050 (Belgium); Greene, J.P.; Henderson, D.J.; Jiang, C.L. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Kashiv, Y. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556-5670 (United States); Kay, B.P.; Lee, H.Y.; Marley, S.T. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Nakanishi, T. [Faculty of Chemistry, Institute of Science and Engineering, Kanazawa University (Japan); Pardo, R.C.; Patel, N.; Rehm, K.E. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Robertson, D. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556-5670 (United States); and others


    The extinct p-process nuclide {sup 146}Sm (t{sub 1/2} = 103 {+-} 5 Myr) is known to have been present in the Early-Solar System and has been proposed as an astrophysical chronometer. {sup 146}Sm is also intensely used to date meteorite and planetary differentiation processes, enhancing the importance of an accurate knowledge of the {sup 146}Sm half-life. We are engaged in a new determination of the {sup 146}Sm half-life in which the {sup 146}Sm/{sup 147}Sm atom ratio is determined by accelerator mass spectrometry at the ATLAS facility of Argonne National Laboratory. In order to reduce systematic errors in the AMS determination of the {sup 146}Sm/{sup 147}Sm ratios (in the range of 10{sup -7}-10{sup -9}), {sup 146}Sm and {sup 147}Sm ions were alternately counted in the same detector in the focal plane of a gas-filled magnet, respectively in continuous-wave and attenuated mode. Quantitative attenuation is obtained with the 12 MHz pulsed and ns-bunched ATLAS beam by chopping beam pulses with an RF sweeper in a ratio (digitally determined) down to 1:10{sup 6}. The experiments and preliminary results are discussed.


    Cunningham, B.B.; Asprey, L.B.


    The microgram scale isolation and preparation of pure compounds of americium is described. Data are presented to show that the alpha-half-life of the isotope Am{sup 241} is 490 {+-} 14 years. The absorption spectrum of Am(III) in 1M nitric acid in the range 3500-8000 mu is given. The wave lengths of 10 of the most prominent lines in the copper spark emission spectrum of americium are given to the nearest 0.01 {angstrom}. Evidence is presented to show that the potential for the Am(III)-Am(IV) couple in acid solution is more negative than -2v and that the potential for the Am(II)-Am(III) couple is more positive than +0.9v.

  11. New limit for the half-life of double beta decay of $^{94}$Zr to the first excited state of $^{94}$Mo

    Dokania, N; Gupta, G; Pal, S; Pillay, R G; Rath, P K; Tretyak, V I; Garai, A; Krishnamoorthy, H; Ghosh, C; Raina, P K; Bhushan, K G


    Double Beta Decay is a phenomenon of fundamental interest for particle physics and the study of these transitions to the excited states is of relevance to the calculation of Nuclear Transition Matrix Element for the process. In the present work, double beta decay of $^{94}$Zr to the $2^{+}_{1}$ excited state of $^{94}$Mo at 871.1 keV is studied using a low background $\\sim$ 250 cm$^3$ HPGe detector. No evidence of this decay was found with a 232 g.y exposure of natural Zirconium. The lower half-life limit obtained for the double beta decay of $\\rm^{94}Zr$ to the $2^{+}_{1}$ excited state of $\\rm^{94}Mo$ is $T_{1/2} > 6.1 \\times 10^{19}$ y at 90\\% C.L. ($T_{1/2} > 2.0 \\times 10^{20}$ y at 68\\% C.L.), a significant improvement by an order of magnitude over the existing experimental limit at 68\\% C.L.

  12. Precision measurement of the half-life and branching ratio of the T=1/2 mirror $\\beta$-decay of $^{37}$K

    We propose to study the T=1/2 mirror $\\beta$-decay of $^{37}$K. Nuclear mirror $\\beta$-decay is a competitive means to test the electroweak model by means of the high-precision measurement of V$_{ud}$ element of the CKM quark mixing matrix. One key ingredient to obtain V$_{ud}$ is the force of the transition, Ft, which has to be determined with a relative precision below 10$^{−3}$. This quantity is related to the half-life T$_{1/2}$ of the decaying nucleus, the branching ratio BR for this decay and the mass difference between the mother and daughter nucleus (Q value). Another important feature is the mixing ratio $\\rho$ between the Fermi and the Gamow-Teller character of the transition. In most cases, $\\rho$ is the major contributor to the uncertainty on Ft. Available data concerning T$_{1/2}$ and BR of $^{37}$K suffer from a lack of precision that will be easily reduced by a dedicated experiment.

  13. Analytical expression for the α-decay half-life and understanding the data including very long life-times and superheavy nuclei

    Sahu, Basudeb


    An analytically solvable composite potential that can closely reproduce the combined potential of an α+nucleus system consisting of attractive nuclear and repulsive electrostatic potentials is developed. The exact s-wave solution of the Schrödinger equation with this potential in the interior region and the outside Coulomb wave function are used to give a heuristic expression for the width or half-life of the quasibound state at the accurately determined resonance energy, called the Q value of the decaying system. By using the fact that for a relatively low resonance energy, the quasibound state wave function is quite similar to the bound state wave function where the amplitude of the wave function in the interaction region is very large as compared to the amplitude outside, the resonance energy could easily be calculated from the variation of relative probability densities of inside and outside waves as a function of energy. By considering recent α-decay systems, the applicability of the model is demonstrated with excellent explanations being found for the experimental data of Q values and half-lives of a vast range of masses including superheavy nuclei and nuclei with very long lifetimes (of order 1022 s). Throughout the application, by simply varying the value of a single potential parameter describing the flatness of the barrier, we obtain successful results in cases with as many as 70 pairs of α+daughter nucleus systems.

  14. Neutron activation of natural materials in a PWR spectrum: feedback on {sup 116m}In relative γ emission intensities and half-life

    Gruel, Adrien; Geslot, Benoit; Di Salvo, Jacques; Blaise, Patrick; Girard, Jean-Michel; Destouches, Christophe [CEA, DEN, SPEx, Cadarache, F-13108 St Paul lez Durance (France)


    During the MAESTRO program, carried out between 2011 and 2014 in MINERVE zero power reactor, common Gen-II and Gen-III light water reactor materials were irradiated. For some of these materials, the decay of their activation products was also measured by γ spectrometry. Initially devoted to the measurement of the integral capture cross section by activation and reactivity-oscillation method, these results can also provide useful information on decay data of various radionuclides. This approach of this experiment led to a common roadmap shared by the Experimental Physics Section and the Henri Becquerel National Laboratory to improve decay data in nuclear data libraries. Results discussed in this paper concern the relative emission intensities of the main γ rays of {sup 116m}In. Six irradiations of samples with various physical forms of {sup nat}In were carried out. Measurements were analyzed using decay data from several evaluations and it is shown that γ ray activities are not consistent. Analyses were carried out to provide new relative γ emission intensities from these measurements. The {sup 116m}In half-life has also been measured and shows a good agreement with existing values. Finally, an overview of the foreseen results on additional decay data from the MAESTRO program is given. (authors)

  15. Upregulation of the mammalian X chromosome is associated with enhanced transcription initiation, MOF-mediated H4K16 acetylation, and longer RNA half-life

    Deng, Xinxian; Berletch, Joel B.; Ma, Wenxiu; Nguyen, Di Kim; Noble, William S.; Shendure, Jay; Disteche, Christine M.


    SUMMARY X upregulation in mammals increases levels of expressed X-linked transcripts to compensate for autosomal bi-allelic expression. Here, we present molecular mechanisms that enhance X expression at transcriptional and posttranscriptional levels. Active mouse X-linked promoters are enriched in the initiation form of RNA polymerase II (PolII-S5p) and in specific histone marks including H4K16ac and histone variant H2AZ. The H4K16 acetyltransferase MOF, known to mediate the Drosophila X upregulation, is also enriched on the mammalian X. Depletion of MOF or MSL1 in mouse ES cells causes a specific decrease in PolII-S5p and in expression of a subset of X-linked genes. Analyses of RNA half-life datasets show increased stability of mammalian X-linked transcripts. Both ancestral X-linked genes, defined as those conserved on chicken autosomes, and newly acquired X-linked genes are upregulated by similar mechanisms but to a different extent, suggesting that subsets of genes are distinctly regulated dependent on their evolutionary history. PMID:23523075

  16. Precision measurement of the half-life and the $\\beta$-decay Q value of the superallowed 0$^{+}\\rightarrow$ 0$^{+}\\beta$-decay of $^{38}$Ca


    We propose to study the $\\beta$-decay of $^{38}$Ca. In a first instance, we intend to perform a high-precision study of the half-life of this nucleus as well as a measurement of its $\\beta$-decay Q-value with ISOLTRAP. At a later stage, we propose to study its decay branches to determine the super-allowed branching ratio with high precision. These measurements are essential to improve our understanding of the theoretical corrections (in particular the $\\delta$c correction factor) needed to calculate the universal Ft value from the ft value determined for individual nuclei. For this nucleus, the correction factor is predicted to increase significantly as compared to the nine well-studied nuclei between $^{10}$C and $^{54}$Co and the model calculations used to determine the corrections, in particular the shell-model calculations, are well under control in this mass region. Therefore, the T$_{Z}$= -1 nuclei between A=18 and A=38 are ideal test cases for the correction factors which limit today the precision on t...

  17. Ligand-substitution mode capillary electrophoretic reactor: extending capillary electrophoretic reactor toward measurement of slow dissociation kinetics with a half-life of hours.

    Iki, Nobuhiko; Takahashi, Mariko; Takahashi, Toru; Hoshino, Hitoshi


    A method employing capillary electrophoresis (CE) was developed to determine the rate constant of the very slow spontaneous dissociation of a complex species. The method uses a CE reactor (CER) to electrophoretically separate components from a complex zone and, thus, spontaneously dissociate a complex. The dissociation is accelerated by ligand substitution (LS) involving a competing ligand added to the electrophoretic buffer. The LS-CER method is validated using the dissociation of a Ti(IV)-catechin complex and EDTA as a competing ligand. There is good agreement between the spontaneous dissociation rate constant (k(d) = (1.64 +/- 0.63) x 10(-4) s(-1)) and the rate constant obtained by a conventional batchwise LS reaction (k(d) = (1.43 +/- 0.04) x 10(-4) s(-1)). Furthermore, the usefulness of the method is demonstrated using a Ti(IV)-tiron complex, for which k(d) = (0.51 +/- 0.43) x 10(-4) s(-1), corresponding to a half-life (t(1/2)) of 3.8 h. Notably, a single run of LS-CER for the Ti(IV) complex is completed within 40 min, implying that LS-CER requires a considerably shorter measurement time (roughly equal to t(1/2)) than conventional CER. LS-CER can be widely applied to determine the spontaneous dissociation rates of inorganic diagnostic and therapeutic reagents as well as of biomolecular complexes.

  18. Research on Half-life Measuring Index of Chinese Psychology Science Based on Bibliometrics%基于文献计量学的我国心理学学科半衰期分析



    文章对心理学学科文献的引用和被引情况进行统计分析,通过学科文献被引半衰期和引用半衰期指标及其相关影响因素的分析,发现:心理学学科引用半衰期明显长于被引半衰期;心理学学科非常注重参考和借鉴国外的研究成果,但引用外文文献的时效相对滞后,说明我国心理学研究落后于国际水平;基础心理学半衰期最长,发展与教育心理学半衰期最短,比较符合偏理论的学科半衰期较长,偏应用的学科半衰期较短的规律。%This paper makes a statistical analysis of research papers' citation. Through analyzing the indexes of half- life of literature and the reference factors, it is found that citing half-life is longer than cited half-life in psychology. It is important to take reference of foreign research achievements in psychology, but the cited foreign papers are lagging, which shows psychology in China lags behind international level. The half-life of basic psychology is longest, while the half-life of development and education psychology is shortest, which shows the rule that half-life of discipline that focus more on theory is longer than the discipline that focus more on application.

  19. Studies on the mechanism of the epileptiform activity induced by U18666A. II. concentration, half-life and distribution of radiolabeled U18666A in the brain

    Cenedella, R.J.; Sarkar, C.P.; Towns, L.


    The concentration, half-life, and distribution in brain of U18666A, a drug that can drastically alter cerebral lipids and induce a chronic epileptiform state, was determined following both acute and chronic drug administration. U18666A specifically labeled with tritium was prepared by custom synthesis. Brain levels of 1 x 10(-6)M and higher were reached soon after giving an acute 10-mg/kg dose (i.p. or s.c.) of U18666A containing 7-/sup 3/H-U18666A of known specific activity. A steady state concentration of 1 to 2 x 10(-6)M was reached with chronic injection of 10 mg/kg every 4th day, a treatment schedule that results in altered brain lipids and induction of epilepsy if begun soon after birth. The disappearance of U18666A from both brain and serum was described by two similar biexponential processes, a brief rapid clearance (t1/2 . 10 h) and a sustained and much slower one (t1/2 . 65 h). Brain levels of the drug were about 10 times higher than serum at all times examined. Few differences were seen in the regional distribution of radiolabeled drug in brain as determined by both direct analysis and by autoradiographic examination; but the drug did concentrate in lipid-rich subcellular fractions. For example, the synaptosome and myelin fractions each contained about 25-35% of both the total /sup 3/H-labeled drug and total lipid in whole brain. The lipid composition of these fractions was drastically altered in treated animals. In conclusion, the chronic epileptiform state induced by U18666A does not appear to involve localization of the drug in a specific brain region or particular cell type. Rather, the condition could involve localization of the drug in lipid-rich membranes and marked changes in the composition of these membranes.

  20. Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma.

    Westerman, P; Glanzmann, T; Andrejevic, S; Braichotte, D R; Forrer, M; Wagnieres, G A; Monnier, P; van den Bergh, H; Mach, J P; Folli, S


    In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo.

  1. Use of expression-enhancing terminators in Saccharomyces cerevisiae to increase mRNA half-life and improve gene expression control for metabolic engineering applications.

    Curran, Kathleen A; Karim, Ashty S; Gupta, Akash; Alper, Hal S


    Control of gene and protein expression of both endogenous and heterologous genes is a key component of metabolic engineering. While a large amount of work has been published characterizing promoters for this purpose, less effort has been exerted to elucidate the role of terminators in yeast. In this study, we characterize over 30 terminators for use in metabolic engineering applications in Saccharomyces cerevisiae and determine mRNA half-life changes to be the major cause of the varied protein and transcript expression level. We demonstrate that the difference in transcript level can be over 6.5-fold even for high strength promoters. The influence of terminator selection is magnified when coupled with a low-expression promoter, with a maximum difference in protein expression of 11-fold between an expression-enhancing terminator and the parent plasmid terminator and over 35-fold difference when compared with a no-terminator baseline. This is the first time that terminators have been investigated in the context of multiple promoters spanning orders of magnitude in activity. Finally, we demonstrate the utility of terminator selection for metabolic engineering by using a mutant xylose isomerase gene as a proof-of-concept. Through pairing an expression-enhancing terminator with a low-expression promoter, we were able to achieve the same phenotypic result as with a promoter considerably higher in strength. Moreover, we can further boost the phenotype of the high-strength promoter by pairing it with an expression-enhancing terminator. This work highlights how terminator elements can be used to control metabolic pathways in the same way that promoters are traditionally used in yeast. Together, this work demonstrates that terminators will be an important part of heterologous gene expression and metabolic engineering for yeast in the future.

  2. Environmental Metabolic Footprinting (EMF) vs. half-life: a new and integrative proxy for the discrimination between control and pesticides exposed sediments in order to further characterise pesticides' environmental impact.

    Salvia, Marie-Virginie; Ben Jrad, Amani; Raviglione, Delphine; Zhou, Yuxiang; Bertrand, Cédric


    Pesticides are regularly used for a variety of applications and are disseminated throughout the environment. These substances may have significant negative impacts. To date, the half-life, t1/2, was often used to study the fate of pesticides in environmental matrices (water, soil, sediment). However, this value gives limited information. First, it does not evaluate the formation of by-products, resulting in the need for additional experiments to be performed to evaluate biodegradation and biotransformation products. T1/2 also fails to consider the chemical's impact on biodiversity. Resilience time, a new and integrative proxy, was recently proposed as an alternative to t1/2, with the potential to evaluate all the post-application effects of the chemical on the environment. The 'Environmental Metabolic Footprinting' (EMF) approach, giving an idea of the resilience time, was used to evaluate the impact of botanicals on soil. The goal is to optimise the EMF to study the impact of a microbial insecticide, the Bacillus thuringiensis israelensis (Bti), on sediment. The difficulty of this work lies in the commercial solution of Bti that is really complex, and this complexity yields chromatograms that are extremely difficult to interpret; t1/2 cannot be used. No methodologies currently exist to monitor the impact of these compounds on the environment. We will test the EMF to determine if it is sensitive enough to tolerate such complex mixtures. A pure chemical insecticide, the α-cypermethrin, will be also studied. The article shows that the EMF is able to distinguish meta-metabolome differences between control and exposed (with Bti) sediments.

  3. 长效人白细胞介素4拮抗剂的研究%Interleukin-4 antagonists with longer half-life in plasma

    宋西勇; 唱韶红; 刘波; 巩新; 吴军


    Objective To develop an interleukin-4(IL-4) antagonist named M5-IgG1Fc protein constructed by genetic engineering of antibody Fc fragment-cytokine mutein fusion protein which has a long half-life time in plasma.M5-IgG1 Fc protein binds to IL-4 receptor but cannot activate downstream signalling pathway , which provides a basis for drug develop-ment for allergic diseases .Methods The synthesized interleukin-4 mutant gene ( named M5 ) was cloned into the expres-sion vector pBV220 and transformed into E.coli DH5α.Chimeric gene M5-IgG1Fc obtained by overlap extension (SOE) method was transformed into glycoengineered Pichia pastoris GJK01 through expression vector pPICZαA .Then M5-IgGFc fusion protein was obtained by protein purification after being induced by methanol in 72 hours.The anti-IL-4 biologicial ac-tivity assay of M5 and M5-IgG1 Fc was performed with CTLL-2/IL-4R cells and detected with MTT colormetry .Finally,the half-life time of M5 and M5-IgG1 Fc protein in mice was compared by detecting the remaining amount in plasma with ELISA kit.Results The M5 protein expressed in E.coli and M5-IgG1 Fc fusion protein expressed in P.pastoris GJK01 both had IL-4 antagonistic bioactivity .The EC50 of both, which inhibited 5.6 ×10 -2 nmol/ml of IL-4, were 0.31 ±0.05 and 0.77 ± 0.03 nmol/ml,respectively.The maximum of M5 in plasma at 0.5 h was 5.8 ×10 -2 nmol/ml but the remaining amount was 2.8%of the maximum at 2 h.M5 protein could not be detected after administration at 8 h because of the detection line . The maximum of M5-IgG1 Fc fusion protein was 4.7 ×10 -2 nmol/ml,while fusion protein M5-IgG1 Fc decreased to 4.3%of its maximum at 120 h and could not be detected at 168 h.Conclusion M5 protein has IL-4 antagonistic bioactivity .M5-IgG1 Fc fusion protein expressed in glycoengineered P.pastoris GJK01 has IL-4 antagonistic bioactivity and long retention time in mice,which can be potentially used for treatment of allergic diseases .%目的

  4. Real-time RT-PCR analysis of mRNA decay: half-life of Beta-actin mRNA in human leukemia CCRF-CEM and Nalm-6 cell lines

    Barredo Julio C


    Full Text Available Abstract Background We describe an alternative method to determine mRNA half-life (t1/2 based on the Real-Time RT-PCR procedure. This approach was evaluated by using the β-actin gene as a reference molecule for measuring of mRNA stability. Results Human leukemia Nalm-6 and CCRF-CEM cells were treated with various concentrations of Actinomycin D to block transcription and aliquots were removed periodically. Total RNA was isolated and quantified using the RiboGreen® fluorescent dye with the VersaFluor Fluorometer System. One μg of total RNA was reverse transcribed and used as template for the amplification of a region of the β-actin gene (231 bp. To generate the standard curve, serial ten-fold dilutions of the pBactin-231 vector containing the cDNA amplified fragment were employed, β-actin mRNAs were quantified by Real-Time RT-PCR using the SYBR® Green I fluorogenic dye and data analyzed using the iCycle iQ system software. Using this method, the β-actin mRNA exhibited a half-life of 6.6 h and 13.5 h in Nalm-6 and CCRF-CEM cells, respectively. The t1/2 value obtained for Nalm-6 is comparable to those estimated from Northern blot studies, using normal human leukocytes (5.5 h. Conclusions We have developed a rapid, sensitive, and reliable method based on Real-Time RT-PCR for measuring mRNA half-life. Our results confirm that β-actin mRNA half-life can be affected by the cellular growth rate.

  5. Quantum Yields of Decomposition and Homo-Dimerization of Solid L-Alanine Induced by 7.2 eV Vacuum Ultraviolet Light Irradiation: An Estimate of the Half-Life of L-Alanine on the Surface of Space Objects

    Izumi, Yudai; Nakagawa, Kazumichi


    One of the leading hypotheses regarding the origin of prebiotic molecules on primitive Earth is that they formed from inorganic molecules in extraterrestrial environments and were delivered by meteorites, space dust and comets. To evaluate the availability of extraterrestrial amino acids, it is necessary to examine their decomposition and oligomerization rates as induced by extraterrestrial energy sources, such as vacuum ultraviolet (VUV) and X-ray photons and high energy particles. This paper reports the quantum yields of decomposition ((8.2 ± 0.7) × 10-2 photon-1) and homo-dimerization ((1.2 ± 0.3) × 10-3 photon-1) and decomposition of the dimer (0.24 ± 0.06 photon-1) of solid l-alanine (Ala) induced by VUV light with an energy of 7.2 eV. Using these quantum yields, the half-life of l-Ala on the surface of a space object in the present earth orbit was estimated to be about 52 days, even when only photons with an energy of 7.2 eV emitted from the present Sun were considered. The actual half-life of solid l-Ala on the surface of a space object orbit around the present day Earth would certainly be much shorter than our estimate, because of the added effect of photons and particles of other energies. Thus, we propose that l-Ala needs to be shielded from solar VUV in protected environments, such as the interior of a meteorite, within a time scale of days after synthesis to ensure its arrival on the primitive Earth.

  6. Shiga toxin type 2 (Stx2), a potential agent of bioterrorism, has a short distribution and a long elimination half-life, and induces kidney and thymus lesions in rats.

    Liu, Yue-Nan; Wang, Sheng-Han; Li, Tao; Wang, Qin; Tu, Wei; Cai, Kun; Hou, Xiao-Jun; Tian, Ren-Mao; Gao, Xiang; Liu, Hao; Xiao, Le; Shi, Jing; Cheng, Yuan-Guo; Li, Jian-Chun; Wang, Hui


    Shiga toxin type 2, a major virulence factor produced by the Shiga toxin-producing Escherichia coli, is a potential toxin agent of bioterrorism. In this study, iodine-125 (125I) was used as an indicator to describe the in vivo Stx2 biodistribution profile. The rats were injected intravenously (i.v.) with 125I-Stx2 at three doses of 5.1-127.5 μg/kg body weight. Stx2 had a short distribution half-life (t (1/2)α, less than 6 min) and a long elimination half-life in rat. The toxicokinetics of Stx2 in rats was dose dependent and nonlinear. Stx2 concentrations in various tissues were detected at 5-min, 0.5-h, and 72-h postinjection. High radioactivity was found in the lungs, kidneys, nasal turbinates, and sometimes in the eyes, which has never been reported in previous studies. In a preliminary assessment, lesions were found in the kidney and thymus.

  7. I-Xe systematics of the impact plume produced chondrules from the CB carbonaceous chondrites: Implications for the half-life value of 129I and absolute age normalization of 129I-129Xe chronometer

    Pravdivtseva, O.; Meshik, A.; Hohenberg, C. M.; Krot, A. N.


    0.6 Ma value for 129I half-life. The slopes of I-Xe - Pb-Pb correlation lines plotted for different sets of samples for Shallowater normalization are always ⩽1. Assuming uranium half-life values are correct; this restricts the half-life of 129I to ⩽15.7 Ma.

  8. Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life

    Judit Zsuga


    Full Text Available The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling. The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases, provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine. Although adenosine metabolism can be inhibited several ways (in order to prevent the rapid elimination of adenosine administered to construct concentration–effect (E/c curves for the determination, the consequent accumulation of endogenous adenosine biases the results. To address this problem, we previously proposed a method, by means of which this bias can be mathematically corrected (utilizing a traditional receptor theory-independent approach. In the present investigation, we have offered in silico validation of this method by simulating E/c curves with the use of the operational model of agonism and then by evaluating them using our method. We have found that our method is suitable to reliably assess the receptor reserve for adenosine in our recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptor reserve for rapidly eliminating agonists in general. In addition, we have disclosed a possible interference between FSCPX (8-cyclopentyl-N3-[3-(4-(fluorosulfonylbenzoyloxypropyl]-N1-propylxanthine, an irreversible A1 adenosine receptor antagonist, and NBTI (S-(2-hydroxy-5-nitrobenzyl-6-thioinosine, a nucleoside transport inhibitor, i.e., FSCPX may blunt the effect of NBTI.

  9. Human FcRn can mediate the transport across intestinal mucosal barrier and prolong the half-life of rabbit IgG in vivo

    Guangchang Pang


    Full Text Available FcRn (neonatal Fc receptor plays an important role in IgG transportation, antigen presentation and signal transmission. In this study, the complement fixation test and flow cytometry test were performed to verify whether the heterologous antibody could be transmitted to the serum or leukocyte with FcγR (Fc gamma receptor across the intestinal mucosa. The results showed that rabbit anti-bovine IgG could be detected in both the serum and the leukocytes, which indicated that the heterologous antibody could transport across the intestinal mucosa to enter the blood and be effectively delivered to the leukocytes with FcγR. In addition, the results also showed that the rabbit anti-bovine IgG still could be detected in the leukocyte group (P=0.044<0.05 after 21 days. It indicated that the rabbit IgG could exist in the body for a long term (up to 21 days after being transported to the cells containing FcγR.

  10. Influência dos sucos de frutas sobre a biodisponibilidade e meia-vida dos medicamentos Influence of fruit juices on bioavailability and half-life of drugs

    Carolina Mariante de Abreu


    -glycoproteín, organic anion transporter polypeptide - OATP. Based on the data above, the aforementioned article seeks information on interaction events involving the co-administration of medications and fruit juices. The review was based on research performed in different databases and related books. The results showed a significant number of interactions, identified in experimental studies, cases-controls and case report. References to the potentiation of an effect, or to therapeutic inefficacy, as a result of the association of pharmaceuticals with fruit juice, were mentioned by several authors, which justify the relevance of diagnosing these phenomenon.

  11. Modification of the Fc Region of a Human Anti-oncostatin M Monoclonal Antibody for Higher Affinity to FcRn Receptor and Extension of Half-life in Cynomolgus Monkeys.

    Nnane, Ivo P; Han, Chao; Jiao, Qun; Tam, Susan H; Davis, Hugh M; Xu, Zhenhua


    The purpose of this study was to evaluate the pharmacokinetics (PK) of anti-oncostatin M (OSM) IgG1 monoclonal antibodies, CNTO 1119 and its Fc variant (CNTO 8212), which incorporates the LS(Xtend) mutation to extend terminal half-life (T1/2 ), after a single intravenous (IV) or subcutaneous (SC) administration in cynomolgus monkeys, and to predict human PK. In study 1, single doses of CNTO 1119 and CNTO 8212 were administered IV or SC at 3 mg/kg to cynomolgus monkeys (n = 3 per group). In study 2, single doses of CNTO 8212 were administered IV at 1, 5 or 20 mg/kg, or SC at 5 mg/kg to cynomolgus monkeys (n = 5 per group). Serial blood samples were collected for assessment of serum concentrations of CNTO 1119 and/or CNTO 8212. A two-compartment population PK model with first-order elimination was utilized to simultaneously describe the serum concentrations of CNTO 1119 and CNTO 8212 over time after IV and SC administration in cynomolgus monkeys. The typical population PK parameter estimates for CNTO 1119 in cynomolgus monkeys were clearance (CL) = 2.81 mL/day/kg, volume of distribution of central compartment (V1 ) = 31.3 mL/kg, volume of distribution of peripheral compartment (V2 ) = 23.3 mL/kg, absolute bioavailability (F) = 0.84 and T1/2 = 13.4 days. In comparison, the typical population PK parameter estimates for CNTO 8212 in cynomolgus monkeys were CL = 1.41 mL/day/kg, V1 = 39.8 mL/kg, V2 = 32.6 mL/kg, F = 0.75 and T1/2 = 35.7 days. The mean CL of CNTO 8212 was ~50% lower compared with that for CNTO 1119 in cynomolgus monkeys. The overall volume of distribution (V1 +V2 ) for CNTO 8212 was about 32% larger compared with that for CNTO 1119, but generally similar to the vascular volume in cynomolgus monkeys. The T1/2 of CNTO 8212 was significantly (p monkeys. Thus, the modification of the Fc portion of an anti-OSM IgG1 mAb for higher FcRn binding affinity resulted in lower systemic clearance and a longer terminal half-life in cynomolgus monkeys. CNTO 8212

  12. Development of controller of acquisition and sample positioner for activation for use in measurements of short half-life radioisotopes; Desenvolvimento de dispositivo movimentador automatizado de amostras com vista a aplicacao em medidas de radioisotopos que possuem curto tempo de meia-vida

    Secco, Marcello


    High resolution gamma spectroscopy measurements have several applications. Those involving short half-life radioisotope measurements may present low precision problems when the radioactive source is far from detector end cup and in the very high activity situations also can present accuracy loss due to dead time and pile-up effects. A way to overcome these problems is changing the source detector distance as the activity is decreasing, and thereby maximizing the statistical counting. In the present study, the Controller of Acquisition and Sample Positioner for Activation (CASPA) was developed. It is a low cost and weight device, made with low atomic number materials designed to assist gamma spectroscopy measurements, which is able to control the distance between the source and the detector, even allowing that there is a change of this distance during the measurement process. Because it is automated it optimizes the time of the operator, who has complete freedom to program their routine measurements in the device besides minimizing the radiation dose in the operator. An interface that allow the user control the CASPA system and to program the acquisition system was created. Tests aiming to optimize the operation of CASPA system were carried out and the safety of the CASPA operation was verified, it was not presented any failure during their tests. It was applied the repeatability tests by the acquisition {sup 60}Co standard source and was found that the positioning of automated system has reproduced the results of static system with a 95% of confidence level. (author)

  13. Oncology Journals Cited Half - life and Its Connection with Other Indicators Such as Impact Factors and Total Cited Frequen%肿瘤医学期刊被引半衰期及其与影响因子、总被引频次等计量指标的关系



    对《2011年版中国期刊引证报告(扩刊版)》中肿瘤医学期刊被引半衰期、影响因子、引用半衰期、总被引频次、平均引文数等的相关关系进行分析,并对期刊编辑和期刊管理工作提出建议。%The paper analyzes the connection among citated half - life, impact factors, citation half - life, total cited frequency of oncology journals included in " Chinese S & T Journal Citation Report (2011 )", proposes advices on journal editing and management work.

  14. Measurement of the double- β decay half-life of 136Xe with the KamLAND-Zen experiment

    Gando, A.; Gando, Y.; Hanakago, H.; Ikeda, H.; Inoue, K.; Kato, R.; Koga, M.; Matsuda, S.; Mitsui, T.; Nakada, T.; Nakamura, K.; Obata, A.; Oki, A.; Ono, Y.; Shimizu, I.; Shirai, J.; Suzuki, A.; Takemoto, Y.; Tamae, K.; Ueshima, K.; Watanabe, H.; Xu, B. D.; Yamada, S.; Yoshida, H.; Kozlov, A.; Yoshida, S.; Banks, T. I.; Detwiler, J. A.; Freedman, S. J.; Fujikawa, B. K.; Han, K.; O’Donnell, T.; Berger, B. E.; Efremenko, Y.; Karwowski, H. J.; Markoff, D. M.; Tornow, W.; Enomoto, S.; Decowski, M. P.


    We present results from the KamLAND-Zen double-beta decay experiment based on an exposure of 77.6 days with 129 kg of 136Xe. The measured two-neutrino double-beta decay half-life of 136Xe is T$2ν\\atop{1/2}$ = 2.38 ± 0.02(stat) ± 0.14(syst) x1021 yr, consistent with a recent measurement by EXO-200. We also obtain a lower limit for the neutrinoless double-beta decay half-life, T$0ν\\atop{1/2}$ > 5.7 x 1024 yr at 90% C.L.

  15. Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: a comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR.

    Suzuki, Takuo; Ishii-Watabe, Akiko; Tada, Minoru; Kobayashi, Tetsu; Kanayasu-Toyoda, Toshie; Kawanishi, Toru; Yamaguchi, Teruhide


    The neonatal FcR (FcRn) binds to the Fc domain of IgG at acidic pH in the endosome and protects IgG from degradation, thereby contributing to the long serum half-life of IgG. To date, more than 20 mAb products and 5 Fc-fusion protein products have received marketing authorization approval in the United States, the European Union, or Japan. Many of these therapeutic proteins have the Fc domain of human IgG1; however, the serum half-lives differ in each protein. To elucidate the role of FcRn in the pharmacokinetics of Fc domain-containing therapeutic proteins, we evaluated the affinity of the clinically used human, humanized, chimeric, or mouse mAbs and Fc-fusion proteins to recombinant human FcRn by surface plasmon resonance analysis. The affinities of these therapeutic proteins to FcRn were found to be closely correlated with the serum half-lives reported from clinical studies, suggesting the important role of FcRn in regulating their serum half-lives. The relatively short serum half-life of Fc-fusion proteins was thought to arise from the low affinity to FcRn. The existence of some mAbs having high affinity to FcRn and a short serum half-life, however, suggested the involvement of other critical factor(s) in determining the serum half-life of such Abs. We further investigated the reason for the relatively low affinity of Fc-fusion proteins to FcRn and suggested the possibility that the receptor domain of Fc-fusion protein influences the structural environment of the FcRn binding region but not of the FcgammaRI binding region of the Fc domain.

  16. Semiperiodo de la literatura científica en Biblioteconomía y Documentación y la influencia de los aspectos temáticos The half-life of scientific literature in library and information science and the influence of thematic issues

    J.A. Martínez-Comeche


    Full Text Available Este trabajo presenta el cálculo del semiperiodo o vida media de las referencias en 28 revistas españolas y anglosajonas de Biblioteconomía y Documentación siguiendo la fórmula de Burton y Kebler, durante el año 2006. Se analiza posteriormente la posible relación con los contenidos presentes en las revistas, y se extraen conclusiones sobre qué temas nucleares del área imponen básicamente dicho semiperiodo, dando lugar a lo que puede considerarse como el semiperiodo de la literatura científica en Biblioteconomía y Documentación, y señalando qué temas tienden a aumentar o disminuir dicho semiperiodo cuando están presentes en una determinada revista. De esta forma el semiperiodo podría considerarse un indicio del contenido temático de la revista.Following the formula developed by Burton and Kebler, this paper presents a calculation of the half-life of bibliographical references appearing in twenty-eight English- and Spanish-language Library and Information Science journals in the year 2006. An analysis of the relationship of this phenomenon to content is carried out in order to identify the nuclear topic areas that in turn determine this half-life. Moreover, the paper provides an assessment of those subject areas for each of the journals studied that tend to lengthen or shorten the half-life of a given bibliographic reference. As such, the bibliographic half-life may be considered an indicator of the thematic inclination of a given journal.

  17. 半衰期为数天的惰性气体和卤素裂变产物在UO2颗粒中的扩散与释放%Diffusion and Release of Noble Gas and Halogen Fission Products With Several Days Half-Life in UO2 Particle



    在考虑吸附效应等物理过程的基础上,得到了裂变产物在UO2颗粒中扩散与释放模型的严格解,并导出了不同反应堆运行状态下裂变产物累积释放份额F(t)、释放-产出比R(t)/B(t)的严格表达式.利用上述结果以及相应的近似解、数值解,对半衰期为数天的惰性气体和卤素裂变产物(131I、131Xem、133Xe和133Xem)在不同堆芯历史条件下的F(t)和R(t)/B(t)进行了比较计算.分析表明,F(t)与R(t)/B(t)的结果均有所差别,但当反应堆运行时间达一定长度后,它们的数值相等.此外,严格解去掉了近似解中不必要的保守性,也比数值解更符合物理实际.%The exact solutions of diffusion and release model of noble gas and halogen fission products in UO2 particle of HTGR were built under the conditions of adsorption effect and other physical processes. The corresponding release fractions (F(t)) and the ratio of release and productive amounts (R (t)/B (t)) of fission products were also derived. Furthermore, the F(t) and R(t)/B(t) of 131I, 131Xem, 133Xe and 133Xem whose half-lifes are several days in UO2 particle with the exact solutions, approximate solutions and corresponding numerical solutions under different temperature histories of reactor core were investigated. The results show that the F(t) and R(t)/B(t) are different in numerical values unless the time of release is long enough. The properties of conservation of exact solutions are much more reasonable than the ones of approximate solutions. It is also found that the results of exact solutions approach the actual working conditions more than the approximate and numerical solutions.

  18. Analytical studies by activation. Part A and B: Counting of short half-life radio-nuclides. Part C: Analytical programs for decay curves; Etudes d'analyse par activation. Parties A et B: le comptage des radio-nucleides de periodes courtes. Partie C: programme de depouillement des courbes de decroissance

    Junod, E. [Commissariat a l' Energie Atomique Grenoble (France). Centre d' Etudes Nucleaires


    Part A and B: Since a radio-nuclide of short half-life is characterized essentially by the decrease in its activity even while it is being measured, the report begins by recalling the basic relationships linking the half-life the counting time, the counting rate and the number of particles recorded. The second part is devoted to the problem of corrections for counting losses due to the idle period of multichannel analyzers. Exact correction formulae have been drawn up for the case where the short half-life radionuclide is pure or contains only a long half-life radio-nuclide. By comparison, charts have been drawn up showing the approximations given by the so-called 'active time' counting and by the counting involving the real time associated with a measurement of the overall idle period, this latter method proving to be more valid than the former. A method is given for reducing the case of a complex mixture to that of a two-component mixture. Part C: The problems connected with the qualitative and quantitative analysis of the decay curves of a mixture of radioactive sources of which one at least has a short half-life are presented. A mathematical description is given of six basic processes for which some elements of Fortran programs are proposed. Two supplementary programs are drawn up for giving an overall treatment of problems of dosage in activation analysis: one on the basis of a simultaneous irradiation of the sample and of one or several known samples, the other with separate irradiation of the unknown and known samples, a dosimeter (activation, or external) being used for normalizing the irradiation flux conditions. (author) [French] Parties A et B: Un radionucleide de periode courte etant defini specialement par la decroissance de son activite pendant la duree meme du comptage, on rappelle en premiere partie de ce rapport les relations fondamentales qui lient periode, temps de comptage, taux de comptage et nombre d'impulsions enregistrees. La

  19. A New Value of 93Zr Half-Life


    <正>93Zr is a long-lived pure β emitter with energies of 60.6 keV (97.5%) and 91.4 keV (2.5%). It is produced by both nuclear fission and neutron capture of 92Zr. 93Zr has considerable attention because of its

  20. What Is the Half-Life of Basketball Teams?

    Hrepic, Zdeslav


    What do basketball teams have in common with radioactive nuclei? It turns out, there is more here than first meets the eye. The National Collegiate Athletic Association (NCAA) basketball tournaments feeds fans' craving when NBA competitions are not in swing, and the college tournament time has been referred to as "March Madness" or…

  1. Using an Authentic Radioisotope to Teach Half-Life

    Liddicoat, Scott; Sebranek, John


    Traditionally nuclear chemistry appears in the last few chapters of chemistry textbooks and is not normally considered a mainstream topic. In addition, some science teachers lack the training or equipment to teach nuclear chemistry. Yet nuclear chemistry is a very important topic that should be taught in all chemistry classrooms. Learning about…

  2. Half Life - The divided life of Bruno Maximovitch Pontecorvo

    CERN. Geneva


    When Bruno Pontecorvo fled to the USSR at the height of the Cold War in 1950, half way through his life, the British Government, MI5 and FBI tried to portray him as scientifically insignificant, and to imply that his disappearance posed no threat to the West. In reality Pontecorvo was already one of the leading experts in nuclear physics, and recently declassified papers reveal that a prime agenda of FBI and MI5 was to cover up their errors. . During his time in the USSR he made major contributions to physics, and justified the sobriquet: "Mr Neutrino". This talk will reveal the background to his sudden flight, and also evaluate his work in theoretical physics in the aftermath of his arrival in Dubna. Previously secret documents now show that he proposed the concept of associated production before Gell Mann and Pais, and he had an idea to discover the neutrino at a reactor. He may be considered the father of neutrino astronomy with his successful prediction that neutrinos from a supernova could be detected, b...

  3. What Is the Half-Life of Basketball Teams?

    Hrepic, Zdeslav


    What do basketball teams have in common with radioactive nuclei? It turns out, there is more here than first meets the eye. The National Collegiate Athletic Association (NCAA) basketball tournaments feeds fans' craving when NBA competitions are not in swing, and the college tournament time has been referred to as "March Madness" or…

  4. Cosmic-ray half-life of {sup 144}Pm

    Zaerpoor, K.; Dragowsky, M.R.; Krane, K.S. [Physics Department, Oregon State University, Corvallis, Oregon97331 (United States); Chan, Y.D.; Isaac, M.C.; Larimer, R.M.; Macchiavelli, A.O.; Macleod, R.W.; Norman, E.B. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, California94720 (United States); DiGregorio, D.E. [Laboratorio TANDAR-CNEA, Buenos Aires, 1429 (Argentina); Hindi, M.M.; Robinson, S.J. [Physics Department, Tennessee Technological University, Cookeville, Tennessee38505 (United States); Miocinovic, P. [Physics Department, University of California, Berkeley, California94720 (United States)


    In order to test the possibility of using {sup 144}Pm as a clock to measure the mean cosmic-ray confinement time in the Galaxy, we counted a highly purified 1.4 {mu}Ci source of this isotope in GAMMASPHERE and searched for its astrophysically interesting {beta}{sup +} decay branch through the observation of positron-annihilation {gamma} rays in coincidence with the characteristic 697-keV {gamma} ray. Analysis of 57 h of source counting and 15 h of background shows no net signal and results in an upper limit of 3.7 of 511-511-697 keV coincident events. From this result we establish a 90{percent} confidence level upper limit on the branch for this decay mode to be 7.4{times}10{sup {minus}6}{percent}. The implications of this result for the {sup 144}Pm cosmic-ray chronometer problem are discussed. {copyright} {ital 1998} {ital The American Physical Society}

  5. Preliminary Studies on Chlorimuron Degradation in Soil by Effective Microogranisms

    LIU Yaguang


    A wheat (Triticum aestivum L.) bioassay method was used for preliminary determination of chlorimuron degradation in soil by EM (effective microorganisms). Under the conditions of this study, chlorimuron half-life was greater than 30-50 days in soil containing different initial concentrations of chlorimuron. After adding EM, chlorimuron degradation half-life ranged from 10-15 days, which was about 15-30 days shorter than without EM. Chlorimuron phate and urea enhanced the ability of EM to degrade chlorimuron, but brown sugar had no significant effect.

  6. Research of influential factors on elimination half life of vancomycin in children with severe pneumonia%万古霉素在重症肺炎患儿体内消除半衰期影响因素的研究

    汪洋; 宋新文; 许琼; 张华年; 徐华


    目的:探讨万古霉素在重症肺炎患儿体内消除半衰期的影响因素.方法:测定29例重症肺炎患儿静滴万古霉素后在消除相两个时间点的血药浓度,并以此估算每位患儿万古霉素的消除半衰期t1/2(β).进一步利用SPSS 13.0软件作多元线性回归分析来考察t1/2(β)与患儿性别、年龄、身高、体质量、给药量及各生化指标之间的相关性.结果:万古霉素t1/2(β)与血清肌酐(CRE,X)及天门冬酸氨基转移酶(AST,Y)浓度呈正相关(P<0.05),与其他统计数据无显著相关性.回归方程为:t1/2(β)=0.360X+0.043Y-6.316(r=0.851,P<0.01).结论:万古霉素在重症肺炎患儿体内的消除速率与肝、肾功能密切相关,应监测血药浓度并根据患儿的自身状况来制订个体化给药方案.%OBJECTIVE To investigate the influential factors on elimination half life of vancomycin in children with severe pneumonia. METHODS The serum vancomycin concentrations at two time points on elimination phase after intravenous drip in each one of 29 children with severe pneumonia were determined, and which were used to calculate the elimination half lives of vancomycin (t1/2beta). The correlation between vancomycin t1/2beta and sex, age, body height, body weight and biochemical indexes of patients was analyzed with multiple linear regression method by SPSS (13. 0) software. RESULTS Vancomycin t1/2betawas positive correlated with serum creatinine concentration(CRE) and AST (P<0. 05), but no significant correlation was noted between t1/2beta and other statistical data. The regression equation was t1/2beta = 0. 360CRE + 0. 043AST - 6. 316(r = 0. 851, P>0. 000). CONCLUSION The elimination rate of vancomycin in children with severe pneumonia was closely correlated with liver and kidney functions, so it's necessary to monitor the serum vancomycin concentration and draw up individualized therapy according the body condition of every patient.

  7. Effects of reclaimed water matrix on fate of pharmaceuticals and personal care products in soil.

    Dodgen, L K; Zheng, W


    Reclaimed water is increasingly used to supplement water resources. However, reclaimed water has a complex matrix, which includes emerging chemical contaminants, that is introduced to the soil when this water is used for irrigation. The effects of microbial activity, dissolved matter, nutrients, and particulate matter in reclaimed water on half-life of 11 pharmaceutical and personal care products (PPCPs) in soil were investigated with 7 treatment waters, namely swine lagoon effluent (either unaltered, sterilized, or filtered and sterilized) and nanopure water (either unaltered or with added nitrogen, phosphorus, or potassium). The extractable residues of the parent PPCPs were measured over 35 d. Lagoon microbial activity was significantly (p ≤ 0.05) related to increased half-life of 4 PPCPs (carbamazepine, fluoxetine, ibuprofen, sulfamethoxazole) by 14-74%, and to decreased half-life of 3 others (caffeine, gemfibrozil, naproxen) by 13-25%. The presence of lagoon dissolved matter was significantly correlated with a 20-110% increase in half-life for 6 PPCPs (caffeine, estrone, gemfibrozil, ibuprofen, naproxen, triclocarban). However, lagoon particulate matter was significantly correlated with 9-52% decrease in half-life for these same compounds, as well as trimethoprim. The levels of nitrogen, phosphorous, and potassium in the lagoon effluent were not significantly related to half-life for most PPCPs, except caffeine. Overall, specific components of reclaimed water matrix had different effects on the soil half-lives of PPCPs, suggesting that the composition of reclaimed water needs to be considered when evaluating PPCP fate after land application. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. A Simulation Stud on Effect of Surface Film—Forming Material on Water Evaporation



    A greenhouse experiment was conducted to investigate the effect of surface film-forming material(SFFM),a mixture of 16-18-octadecanols by emulsification,on water evaporation,Air-dired soil with distilled water was incubated firstly for 7days to reestablish soil biological activity and then for another 7 days atfer treated with SFFM at rates of 0,1,2,4,6,8 and 8 g m-2,respectively,Everyday during the 7-day incubation after addition of SFFM,water losses due to evaporation were measured by an electronic balance.The rate of water evaporation with the addition of SFFM was reduced significantly compared with the control treatment and the effectiveness of SFFM on water evaporation reduced with time.According to the equation expressions of the effect of SFFM on water evaporation ,the half-life of effectiveness of SFFM on water evaporation was introduced and calculated to analyze quantitative relationship between the effectiveness of SFFM on water evaporation and the addition rate of SFFM.The calculaed half-life increased with the addition rate of SFFM and the confidence of the calculated values of the half-life was high,suggesting that the half-life of effectiveness of SFFM on water evaporation could be described quantitaively and may be helpful for ameliorating application method of SFFM and screening surface-film forming materials in order to improve nitrogen fetilizer use efficiency in floodey rice fields.

  9. Toxic and photodynamic effects of toluidine blue on living bull spermatoza

    Duijn, C. van


    1. 1. The effects of vital staining with toluidine blue on the total number of bull spermatozoa moving normally and on their mean velocity and velocity frequency distributions have been investigated with Rikmenspoel's photoelectric method. 2. 2. A significant decrease of the mean half-life period of

  10. Matching the decay half-life with the biological half-life: ImmunoPET imaging with (44)Sc-labeled cetuximab Fab fragment.

    Chakravarty, Rubel; Goel, Shreya; Valdovinos, Hector F; Hernandez, Reinier; Hong, Hao; Nickles, Robert J; Cai, Weibo


    Scandium-44 (t1/2 = 3.9 h) is a relatively new radioisotope of potential interest for use in clinical positron emission tomography (PET). Herein, we report, for the first time, the room-temperature radiolabeling of proteins with (44)Sc for in vivo PET imaging. For this purpose, the Fab fragment of Cetuximab, a monoclonal antibody that binds with high affinity to epidermal growth factor receptor (EGFR), was generated and conjugated with N-[(R)-2-amino-3-(para-isothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N″,N″-pentaacetic acid (CHX-A″-DTPA). The high purity of Cetuximab-Fab was confirmed by SDS-PAGE and mass spectrometry. The potential of the bioconjugate for PET imaging of EGFR expression in human glioblastoma (U87MG) tumor-bearing mice was investigated after (44)Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of ∼12% ID/g at 4 h postinjection) of (44)Sc-CHX-A″-DTPA-Cetuximab-Fab with excellent tumor-to-background ratio, which might allow for same day PET imaging in future clinical studies. Immunofluorescence staining was conducted to correlate tracer uptake in the tumor and normal tissues with EGFR expression. This successful strategy for immunoPET imaging of EGFR expression using (44)Sc-CHX-A″-DTPA-Cetuximab-Fab can make clinically translatable advances to select the right population of patients for EGFR-targeted therapy and also to monitor the therapeutic efficacy of anti-EGFR treatments.

  11. A Simulation Study on Effect of SurfaceFilm-Forming{1mmMaterial on Water Evaporation


    A greenhouse experiment was conducted to investigate the effect ofsurface film-forming material (SFFM), a mixture of1618-octadecanols by emulsification, on water evaporation.Air-dried soil with distilled water was incubated firstly for 7 days toreestablish soil biological activity and then for another 7 days aftertreated with SFFM at rates of 0, 1, 2, 4, 6 and 8 g m{-2,respectively. Everyday during the 7-day incubation after addition ofSFFM, water losses due to evaporation were measured by an electronicbalance. The rate of water evaporation with the addition of SFFM wasreduced significantly compared with the control treatment and theeffectiveness of SFFM on water evaporation reduced with time. Accordingto the equation expressions of the effect of SFFM on water evaporation,the half-life of effectiveness of SFFM on water evaporation wasintroduced and calculated to analyze quantitative relationship betweenthe effectiveness of SFFM on water evaporation and the addition rate ofSFFM. The calculated half-life increased with the addition rate of SFFMand the confidence of the calculated values of the half-life was high,suggesting that the half-life of effectiveness of SFFM on waterevaporation could be described quantitatively and may be helpful forameliorating application method of SFFM and screening surface-filmforming materials in order to improve nitrogen fertilizer useefficiency in flooded rice fields.

  12. Effects of early-life lead exposure on oxidative status and phagocytosis activity in great tits (Parus major)

    Rainio, Miia J.; Eeva, Tapio; Lilley, Thomas; Stauffer, Janina; Ruuskanen, Suvi


    Abstract Lead is a highly poisonous metal with a very long half-life, distributing throughout the body in blood and accumulating primarily in bones and kidney. We studied the short and long-term effects of early-life lead exposure on antioxidant defense and phagocytosis activity in a small passerine

  13. Effects of early-life lead exposure on oxidative status and phagocytosis activity in great tits (Parus major)

    Rainio, Miia J.; Eeva, Tapio; Lilley, Thomas; Stauffer, Janina; Ruuskanen, Suvi


    Abstract Lead is a highly poisonous metal with a very long half-life, distributing throughout the body in blood and accumulating primarily in bones and kidney. We studied the short and long-term effects of early-life lead exposure on antioxidant defense and phagocytosis activity in a small passerine

  14. Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure

    Yin, Meimei; Sillje, Herman H. W.; Meissner, Maxi; van Gilst, Wiek H.; de Boer, Rudolf A.


    Background: Progressive remodeling after myocardial infarction (MI) is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipe

  15. Ca2+ - or Phorbol Ester - Dependent Effect of ATP on a Subpopulation of cAMP Cell-Surface Receptors in Membranes from D. discoideum. A Role for Protein Kinase C

    Haastert, Peter J.M. van; Wit, René J.W. de; Lookeren Campagne, Michiel M. van


    D. discoideum cells contain surface receptors for the chemoattractant cAMP which are composed of fast and slowly dissociating binding sites with half-lifes of respectively about 1 s and 15 s. In membranes prepared by shearing the cells through a Nucleopore filter, ATP has no effect on cAMP-binding a

  16. N-glycosylation increases the circulatory half-life of human growth hormone

    Flintegaard, Thomas V; Thygesen, Peter; Rahbek-Nielsen, Henrik


    Therapeutic use of recombinant GH typically involves daily sc injections. We examined the possibilities for prolonging the in vivo circulation of GH by introducing N-glycans. Human GH variants with a single potential N-glycosylation site (N-X-S/T) introduced by site-directed mutagenesis were...

  17. Endogenous compounds labeled with radionuclides of short half-life-some perspectives

    Roland Långström, Bengt; Karimi, F; Watanabe, Y


    In the article, the strategy and synthesis of some endogenous compounds labeled mainly with (11) C are presented. There are some examples illustrating how endogenous labeled compounds in connection with positron emission tomography have unique properties to describe various biological processes......, and a few examples of the use of tracers labeled with (13) N and (15) O are also discussed. Labeled endogenous compounds may be an important asset to describe the conditions and the status of biological systems and might therefore be a key for the future search of individualized medicine....

  18. Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

    D.J. Janssen; V.P. Carnielli (Virgilio); P.E. Cogo (Paola); S.R. Seidner; I.H.I. Luijendijk; J.L.D. Wattimena (Josias); A.H. Jobe (Alan); L.J.I. Zimmermann (Luc)


    textabstractBecause minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing

  19. Use of daily detector verification data for isotopical half-life determination

    Goncalves, Vitor C.; Zahn, Guilherme S.; Genezini, Frederico A.; Ticianelli, Regina B.; Saiki, Mitiko [Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP. P.O. Box 11049, Sao Paulo, 05422-970 (Brazil)


    In this work, the possibility of using data fromthe daily detector verification routines performed at the Neutron Activation Laboratory of IPEN to determine precise values for the half-lives of {sup 57}Co and {sup 60}Co was evaluated. For this purpose data from 4 of the laboratory's detectors, some spanning for more than 9 years, were inspected, separated in consistent groups, and then analyzed using a robust least-squares fit procedure in order to determine the half-lives. The results allowed for a discussion on the possibilities and limitations of the use of these data for the determination of half-lives.

  20. Investigations of short half-life states from SF of {sup 252}Cf

    Fong, D.; Hwang, J.K.; Ramayya, A.V.; Hamilton, J.H.; Beyer, C.J.; Li, K.; Gore, P.M.; Jones, E.F.; Luo, Y.X. [Vanderbilt University, Physics Department, Nashville, TN (United States); Rasmussen, J.O.; Wu, S.C.; Lee, I.Y.; Fallon, P.; Ginter, T.N. [Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Zhu, S.J. [Tsinghua University, Department of Physics, Beijing (China); Stoyer, M.A.; Asztalos, S.J. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Cole, J.D. [Idaho National Engineering and Environmental Laboratory, Idaho Falls, ID (United States); Ter-Akopian, G.M.; Daniel, A. [Joint Institute for Nuclear Research, Flerov Laboratory for Nuclear Reactions, Dubna (Russian Federation)


    By using different time-gated triple {gamma} coincidence data, the half-lives (T{sub 1/2}) of several short lived states in neutron-rich nuclei have been studied. The first excited states in the ground state bands often decay by delayed {gamma} emission. By creating triple {gamma} coincidence spectra with time windows of 8, 16, 20, 28, and 48 ns, we have studied states with half-lives below 10 ns. The estimated half-lives of {sup 102}Zr, {sup 137}Xe, and {sup 143}Ba are in reasonable agreement with previously reported values. We extract the first estimates of the half lives of the 2{sup +} states in {sup 104}Zr and {sup 152}Ce. (orig.)

  1. Half-Life Learning Curves in the Defense Acquisition Life Cycle


    learning include Smith (1989); Belkaoui (1976, 1986); Nanda (1979); Pegels (1976); Richardson (1978); Towill, and Kaloo (1978); Womer (1979, 1981, 1984...analysis adjusted for learning. Management Science, 24(2), 149–160. Nanda , R. (1979). Using learning curves in integration of production resources

  2. "半条命"当选最佳%Half-Life 2 Voted Best



    @@ As much as Hollywood critics tend to spurn(弃绝)movies involving exploding zombies(巫毒崇拜), video game critics appear to love them. A game centered on the adventures of a scientist who blasts( 毁灭 ) an invading army of zombies has bested a field of rival offerings-including a driving adventure and a game first developed as a U. S. Army training tool-to win a coveted(觊觎的) award from game commentators.

  3. The half-life of the moral dilemma task : A case study in experimental (neuro-) philosophy

    Schleim, Stephan; Clausen, Jens; Levy, Neil


    The pioneering neuroscience of moral decisions studies implementing the moral dilemma task by Joshua Greene and colleagues stimulated interdisciplinary experimental research on moral cognition as well as a philosophical debate on its normative implications. This chapter emphasizes the influence thes

  4. The half-life of the moral dilemma task : A case study in experimental (neuro-) philosophy

    Schleim, Stephan; Clausen, Jens; Levy, Neil


    The pioneering neuroscience of moral decisions studies implementing the moral dilemma task by Joshua Greene and colleagues stimulated interdisciplinary experimental research on moral cognition as well as a philosophical debate on its normative implications. This chapter emphasizes the influence

  5. Average and recommended half-life values for two neutrino double beta decay: upgrade'05

    Barabash, A S


    All existing ``positive'' results on two neutrino double beta decay in different nuclei were analyzed. Using the procedure recommended by the Particle Data Group, weighted average values for half-lives of $^{48}$Ca, $^{76}$Ge, $^{82}$Se, $^{96}$Zr, $^{100}$Mo, $^{100}$Mo - $^{100}$Ru ($0^+_1$), $^{116}$Cd, $^{150}$Nd, $^{150}$Nd - $^{150}$Sm ($0^+_1$) and $^{238}$U were obtained. Existing geochemical data were analyzed and recommended values for half-lives of $^{128}$Te, $^{130}$Te and $^{130}$Ba are proposed. We recommend the use of these results as presently the most precise and reliable values for half-lives.

  6. Average and recommended half-life values for two neutrino double beta decay: upgrade-09

    Barabash, A S


    All existing ``positive'' results on two neutrino double beta decay in different nuclei were analyzed. Using the procedure recommended by the Particle Data Group, weighted average values for half-lives of $^{48}$Ca, $^{76}$Ge, $^{82}$Se, $^{96}$Zr, $^{100}$Mo, $^{100}$Mo - $^{100}$Ru ($0^+_1$), $^{116}$Cd, $^{130}$Te, $^{150}$Nd, $^{150}$Nd - $^{150}$Sm ($0^+_1$) and $^{238}$U were obtained. Existing geochemical data were analyzed and recommended values for half-lives of $^{128}$Te, $^{130}$Te and $^{130}$Ba are proposed. We recommend the use of these results as presently the most precise and reliable values for half-lives.

  7. Average and recommended half-life values for two neutrino double beta decay: upgrade-2013

    Barabash, A S


    All existing positive results on two neutrino double beta decay in different nuclei were analyzed. Using the procedure recommended by the Particle Data Group, weighted average values for half-lives of $^{48}$Ca, $^{76}$Ge, $^{82}$Se, $^{96}$Zr, $^{100}$Mo, $^{100}$Mo - $^{100}$Ru ($0^+_1$), $^{116}$Cd, $^{130}$Te, $^{136}$Xe, $^{150}$Nd, $^{150}$Nd - $^{150}$Sm ($0^+_1$) and $^{238}$U were obtained. Existing geochemical data were analyzed and recommended values for half-lives of $^{128}$Te and $^{130}$Ba are proposed. I recommend the use of these results as the most currently reliable values for half-lives.

  8. Systematics of alpha decay half-life: new evaluations for alpha-emitter nuclides

    Medeiros, E.L.; Rodrigues, M.M.N.; Duarte, S.B.; Tavares, O.A.P. E-mail:


    A semiempirical model based on the quantum mechanical tunnelling mechanism of alpha emission from nuclei has been used to systematize the alpha decay half-lives of a set of 336 nuclides, comprising all the alpha-emitter nuclides whose T{sub 1/2} {sup a}lpha-data for ground-state to ground-state transitions of mutual angular momentum l = 0 are known. With a minimum of data rejection (only {approx} 5% of cases), the procedure has been successful in reproducing quite satisfactorily (within a factor {approx} 2) most of the cases ({approx} 80%) investigated. The few significant discrepancies found between measured and calculated results are analysed and discussed. Also reported is the prediction from the model for possible new alpha-emitter nuclides, namely {sup 180} W, {sup 184} Os, and {sup 228} Ra for which cases the calculated partial alpha decay half-lives fall within the range of half-lives measurable by the current techniques. (author)

  9. Effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds using a modified QSAR model.

    Lim, Seung Joo; Fox, Peter


    The effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds were investigated using a modified half life equation. The potential future pharmaceutical compounds investigated were approximately 2000 pharmaceutical drugs currently undergoing the United States Food and Drug Administration (US FDA) testing. EPI Suite (BIOWIN) model estimates the fates of compounds based on the biodegradability under aerobic conditions. While BIOWIN considered the biodegradability of a compound only, the half life equation used in this study was modified by biodegradability, sorption and cometabolic oxidation. It was possible that the potential future pharmaceutical compounds were more accurately estimated using the modified half life equation. The modified half life equation considered sorption and cometabolic oxidation of halogenated aromatic/aliphatics and nitrogen(N)-heterocyclic aromatics in the sub-surface, while EPI Suite (BIOWIN) did not. Halogenated aliphatics in chemicals were more persistent than halogenated aromatics in the sub-surface. In addition, in the sub-surface environment, the fates of organic chemicals were much more affected by halogenation in chemicals than by nitrogen(N)-heterocyclic aromatics.

  10. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury

    Hong-fei Li; Yi-ru Wang; Hui-ping Huo; Yue-xiang Wang; Jie Tang


    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for g...

  11. Effects of gamma irradiation on microbial load and quality characteristics of veal

    Ebrahim Rahimi


    Full Text Available Background: Veal is a rich nutrient medium that provides a suitable environment for proliferation of veal spoiling microorganisms and common food-borne pathogens. In this study, the effects of irradiation on the veal microbiological quality and half life of minced beef during chilled storage was investigated. Materials and Methods: Twenty samples of minced veal were irradiated with doses of 2, 5, 7, and 10 kGy (Cobalt-60, gamma cell 220 and evaluated for their microbiological quality up to 10 days. Results: The results showed that gamma irradiation reduced the number of microorganisms in all the irradiated minced veal samples, with 2, 5, 7, and 10 kGy (P < 0.01. Moreover, the half life of the samples were increased considerably (P < 0.01. In addition, the results indicated that there was a significant difference in the number of coliformes between untreated and irradiated samples (P < 0.05. While, Staphylococcus aureus could not be detected in the irradiated samples with doses of 7 and 10 kGy. Conclusion: These results indicated that irradiation could be employed as an effective mean to inactivate common food-borne pathogens namely S. aureus and increases the half life of veal.

  12. Evaluation of radon and their daughters concentration and estimative of effective dose in a waste deposits at the ore treatment unity of INB/Pocos de Caldas, Brazil; Avaliacao da concentracao de radonio e seus filhos e estimativa de dose efetiva em um deposito de rejeitos na unidade de tratamento de minerios da INB/Caldas

    Dantas, Marcelino V.A.; Garcia Filho, Oswaldo; Antunes, Marcos M.; Junior, Joao V.S.; Py Junior, Delcy A., E-mail:, E-mail:, E-mail:, E-mail:, E-mail:, E-mail: [Industrias Nucleares do Brasil (UTM/INB), Caldas, MG (Brazil). Unidade de Tratamento de Minerios; Pereira, Wagner S. [Industrias Nucleares do Brasil (UTM/INB), Caldas, MG (Brazil). Unidade de Tratamento de Minerios; Universidade Federal Fluminense (IB/UFF), Niteroi, RJ (Brazil). Inst. de Biologia. Lab. de Radiobiologia e Radiometria Pedro Lopes dos Santos


    This paper conducts a surveillance of radon and their short half-life daughters gas concentration, inside the warehouse due to these gas inhalation. The results showed that the average concentration inside the warehouse ix approximately 700 Bq/m{sup 3} and the effective dose of an IOE, related to that concentration would be 5.0 mSv/year, therefore being 4 times lower than the established limit of 20 mSv/year

  13. Diurnal lamotrigine plasma level fluctuations: clinical significance and indication of shorter half-life with chronic administration

    Nielsen, K.A.; Dahl, M.; Tommerup, E.


    of complaints indicating toxicity requires determination of drug levels when the symptoms are present. Our findings indicate that the t(1/2) of LTG with chronic treatment is shorter than generally assumed, and suggest that a slow-release formulation could be helpful in achieving full seizure control in patients...

  14. Sensitivity Analysis on the Half-Life of Trichloroethylene and the Distribution Coefficient at the Paducah Gaseous Diffusion Plant

    Kopp, Joshua D [Univ of KY, Dept of Civil Engineering


    To determine the future extent of the TCE contamination plume at PGDP, a groundwater and solute transport model has been developed by the Department of Energy (DOE). The model used to perform these calculations is MODFLOWT which is an enhanced groundwater transport model developed by the United States Geological Survey (USGS). MODFLOWT models groundwater movement as well as the transport of species that are subject to adsorption and decay by using a finite difference method (Duffield et al 2001). A significant limitation of MODFLOWT is that it requires large amounts of data. This data can be difficult and expensive to obtain. MODFLOWT also requires excessive computational time to perform one simulation. It is desirable to have a model that can predict the spatial extent of the contaminant plume without as much required data and that does not require excessive computational times. The purpose of this study is to develop and alternative model to MODFLOWT that can produce similar results for possible use in a companion management model. The alternative model used in this study is an artificial neural network (ANN).

  15. In silico prediction of brain exposure: drug free fraction, unbound brain to plasma concentration ratio and equilibrium half-life

    Spreafico, Morena; Jacobson, Matthew P.


    The focus of CNS drug pharmacokinetics programs has recently shifted from determining the total concentrations in brain and blood to considering also unbound fractions and concentrations. Unfortunately, assessing unbound brain exposure experimentally requires demanding in vivo and in vitro studies. We propose a physical model, based on lipid binding and pH partitioning, to predict in silico the unbound volume of distribution in the brain. The model takes into account the partition of a drug into lipids, interstitial fluid and intracellular compartments of the brain. The results are in good agreement with the experimental data, suggesting that the contributions of lipid binding and pH partitioning are important in determining drug exposure in brain. The predicted values are used, together with predictions for plasma protein binding, as corrective terms in a second model to derive the unbound brain to plasma concentration ratio starting from experimental values of total concentration ratio. The calculated values of brain free fraction and passive permeability are also used to qualitatively determine the brain to plasma equilibration time in a model that shows promising results but is limited to a very small set of compounds. The models we propose are a step forward in understanding and predicting pharmacologically relevant exposure in brain starting from compounds’ chemical structure and neuropharmacokinetics, by using experimental total brain to plasma ratios, in silico calculated properties and simple physics-based approaches. The models can be used in central nervous system drug discovery programs for a fast and cheap assessment of unbound brain exposure. For existing compounds, the unbound ratios can be derived from experimental values of total brain to plasma ratios. For both existing and hypothetical compounds, the unbound volume of distribution due to lipid binding and pH partitioning can be calculated starting only from the chemical structure. PMID:23578025

  16. Comparative Study of α Half-life of 210Po in Metal Environment at CIAE with a Reference Value

    ZHAO; Qing-zhang; HE; Ming; DONG; Ke-jun; WANG; Xiao-ming; WANG; Wei; RUAN; Xiang-dong; SHEN; Hong-tao; ZHANG; Hui; DOU; Liang; YANG; Xu-ran; XU; Yong-ning; PANG; Yi-jun; WU; Shao-yong; JIANG; Shan


    The influence of the electron screening on nuclear processes is studied by many scientists.Within the framework of the Gamow theory,a conventional expression for theαdecay probability is essentially given by the product of two factors:the cluster pre-formation and the penetration probabilities.The former may not affected by the electron screening.The second factor may

  17. Fission properties of einsteinium and fermium. [Half-life, kinetic energy release, mass division, prompt neutron emission

    Hoffman, D.C.


    The systematics of the low energy fission of the fermium isotopes is studied considering half-lives, masss division, kinetic-energy release, and accompanying prompt neutron emission. It is shown that the low energy fission of the fermium isotopes is a microcosm of the fission process, exhibiting a wide range of half lives, mass and kinetic energy distributions and varying neutron emission. The trends in the fermium isotopes are considered. 23 references. (JFP)

  18. Experimental implementation and proof of principle for a radionuclidic purity test solely based on half-life measurement

    Jørgensen, Thomas; Jensen, Mikael


    In this paper we present the results of an experimental implementation of the method (Jorgensen et al., 2012) for testing the radionuclidic purity (RNP) of F-18 compounds.The overall limitations of the experimental methods and their possible impacts on RNP detectability have been identified. We...

  19. Lack of effect of tenoxicam on glibornuride kinetics and response.

    Stoeckel, K; Trueb, V; Dubach, U C; Heintz, R C; Ascalone, V; Forgo, I; Hennes, U


    The pharmacokinetics of glibornuride (25 mg i.v.) and the accompanying insulin and glucose responses were characterized in eight human subjects in the presence and absence of steady-state tenoxicam (20 mg p.o./day for 2 weeks). Tenoxicam affected neither the pharmacokinetic parameters of glibornuride (systemic clearance, volume of distribution and biological half-life) nor the responses of plasma insulin and blood glucose to glibornuride. The single i.v. dose of glibornuride had no detectable effect on the kinetics of tenoxicam. PMID:3157397

  20. Effect of ozonation of swimming pool water on formation of volatile disinfection by-products - A laboratory study

    Hansen, Kamilla Marie Speht; Spiliotopoulou, Aikaterini; Cheema, Waqas Akram;


    byproducts during subsequent chlorination. The ozone reaction was observed to behave according to first order kinetics. For tap water half-life was 4 min whilst polluted and unpolluted pool water exhibited half-life of 8 and 11 min, respectively. When ozonation dosage was repeated half-life of ozone...

  1. Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold.

    Hedges, A R; Pypendop, B H; Shilo-Benjamini, Y; Stanley, S D; Ilkiw, J E


    This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration-thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two- and three-compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady-state (L/kg), clearance (mL·min/kg), and terminal half-life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half-life was 23.7 ± 9.1 min, and terminal half-life was 8.9 ± 4.9 h. An effect-compartment model with a simple effect maximum model best predicted the time-course of the effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were 0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002-0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal).

  2. The pharmacodynamic effect of amoxicillin and danofloxacin against Salmonella typhimurium in an in-vitro pharmacodynamic model

    Lindecrona, R.H.; Friis, C.; Aarestrup, Frank Møller


    The pharmacodynamic effect of amoxicillin and danofloxacin against two strains of Salmonella typhimurium was examined in an in-vitro pharmacodynamic model. For amoxicillin, peak concentrations of 1, 2 and 4 mu g ml(-1) and half-lives (t(1/2) of 3 and 15 hours were evaluated. For danofloxacin peak...... concentrations of 0.25, 0.50 and 1.50 mu g ml(-1) and half-lives of 7 and 15 hours were examined. For amoxicillin both the peak concentration and the half-life influenced the pharmacodynamic effect (P

  3. Effects of acute hepatic and renal failure on pharmacokinetics of flunixin meglumine in rats.

    Hwang, Youn-Hwan; Yun, Hyo-In


    The aim of this study was to investigate the effects of hepatic and renal failure on the pharmacokinetics of flunixin in carbon tetrachloride (CCl(4))- and glycerol-treated rats. After intravenous administration of flunixin (2 mg/kg), the plasma concentration of flunixin was measured by high-performance liquid chromatography. Both acute hepatic and renal failure resulted in significantly increased area under the curve (AUC), prolonged elimination half-life (t(1/2β)), and reduced total body clearance (Cl(tot)) compared with respective controls (Pflunixin.

  4. [Effect of temperature on the kinetics of propranolol, theophylline, phenytoin and digoxin in rats (author's transl)].

    Albin, H; Vincon, G; Ploux, D; Dangoumau, J


    1. The effect of chronic hyperthermia (35 degree C for 1 month) on the kinetics of propranolol, theophylline, diphenylhydantoin and digoxin was studied in groups of male Wistar rats. 2. Each compound was administered by intravenous injection, dosage being 2 mg/kg for propranolol, 3 mg/kg for theophylline, 10 mg/kg for phenytoin, and 0.01 mg/Kg for digoxin. 3. Total body clearance was diminished, mainly by an increase in the elimination half-life, for propranolol, theophylline, and digoxin. That of phenytoin remained unchanged. 4. Distribution volume increased slightly with propranolol, theophylline, digoxin.

  5. Pharmacokinetics and pharmacodynamic effects of meloxicam in piglets subjected to a kaolin inflammation model.

    Fosse, T K; Spadavecchia, C; Horsberg, T E; Haga, H A; Ranheim, B


    The pharmacokinetics and the analgesic, anti-inflammatory and antipyretic effects of meloxicam were investigated in a placebo controlled study in 2-week-old piglets. Inflammation was induced by a subcutaneous injection of kaolin in the left metacarpus, and 16 h later, meloxicam (0.6 mg/kg) or saline was administered intramuscularly. The absorption half-life was relatively short (0.19 h) and the elimination half-life was 2.6 h. Mechanical nociceptive threshold testing was used to evaluate the analgesic effect, but no significant effect of the meloxicam treatment was found. The skin temperature of the inflamed area increased after the kaolin injection, but no significant decrease in temperature was found after administration of meloxicam. Only limited pyresis was observed after the kaolin injection, and no significant antipyretic effect of meloxicam was found. The results indicated that this dose of meloxicam had very limited anti-inflammatory and analgesic effects in piglets. © 2010 Blackwell Publishing Ltd.

  6. Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics.

    Pacifici, Gian M


    Phenobarbital is an effective and safe anticonvulsant drug introduced in clinical use in 1904. Its mechanism of action is the synaptic inhibition through an action on GABAA. The loading dose of phenobarbital is 20 mg/kg intravenously and the maintenance dose is 3 to 4 mg/kg by mouth. The serum concentration of phenobarbital is up to 40 µg/ml. Nonresponders should receive additional doses of 5 to 10 mg/kg until seizures stop. Infants with refractory seizures may have a serum concentration of phenobarbital of 100 µg/ml. Phenobarbital is metabolized in the liver by CYP2C9 with minor metabolism by CYP2C19 and CYP2E1. A quarter of the dose of phenobarbital is excreted unchanged in the urine. In adults, the half-life of phenobarbital is 100 hours and in term and preterm infants is 103 and 141 hours, respectively. The half-life of phenobarbital decreases 4.6 hours per day and it is 67 hours in infants 4 week old.

  7. Sex Differences and the Effects of Stress on Subsequent Opioid Consumption in Adult Rats Following Adolescent Nicotine Exposure: A Psychopharmacologic Examination of the Gateway Hypothesis


    from opium. Also included in this class of drugs are synthetic (e.g., methadone and fentanyl) drugs that have actions which mimic the effects of morphine...small molecule with a pKa of7.7 and it has a short half-life (approximately 3.7 hours). Fentanyl has a high lipid solubility and, therefore, it crosses...behaviors, opioid receptors, and dopamine synthesis . Neuropharmacology, 36(2), 251-259. Ba-ttig, K. (1981). Smoking and the behavioral effects

  8. Herb-Drug Interaction: A Case Study of Effect of Ginger on the Pharmacokinetic of Metronidazole in Rabbit

    Okonta, J. M.; Uboh, M.; Obonga, W. O.


    The effect of ginger on the pharmacokinectic of metronidazole was studied using rabbits in a crossover study method. The relevance of this study borders on the wide use of ginger for culinary and phytotherapeutic purposes, and metronidazole that is commonly used for every gastrointestinal complain in our communities without prescription. Ginger significantly increased the absorption and plasma half-life, and significantly decreased the elimination rate constant and clearance of metronidazole (P<0.05). Thus, in clinical practice, the patients should be advised on the serious implication of using both items together. PMID:20046719

  9. The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.


    The effect of pretreatment for 7 days with either roxatidine acetate 75 mg twice daily or cimetidine 200 mg four times daily on the kinetics of antipyrine (AP), trimethadione (TMO) and indocyanine green (ICG) was studied in seven healthy, male, nonsmoking subjects. After pretreatment with cimetidine, the plasma clearances (CL) of AP and TMO were significantly lower and the elimination half-life (t1/2) of AP was significantly increased. The volumes of distribution (V) of AP and TMO were not af...

  10. Herb-drug interaction: A case study of effect of ginger on the pharmacokinetic of metronidazole in rabbit

    Okonta J


    Full Text Available The effect of ginger on the pharmacokinectic of metronidazole was studied using rabbits in a crossover study method. The relevance of this study borders on the wide use of ginger for culinary and phytotherapeutic purposes, and metronidazole that is commonly used for every gastrointestinal complain in our communities without prescription. Ginger significantly increased the absorption and plasma half-life, and significantly decreased the elimination rate constant and clearance of metronidazole ( P< 0.05. Thus, in clinical practice, the patients should be advised on the serious implication of using both items together.

  11. Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles

    Roohi F


    Full Text Available Farnoosh Roohi, Jessica Lohrke, Andreas Ide, Gunnar Schütz, Katrin DasslerMR and CT Contrast Media Research, Bayer Pharma AG, Berlin, GermanyPurpose: Magnetic resonance imaging (MRI, one of the most powerful imaging techniques available, usually requires the use of an on-demand designed contrast agent to fully exploit its potential. The blood kinetics of the contrast agent represent an important factor that needs to be considered depending on the objective of the medical examination. For particulate contrast agents, such as superparamagnetic iron oxide nanoparticles (SPIOs, the key parameters are particle size and characteristics of the coating material. In this study we analyzed the effect of these two properties independently and systematically on the magnetic behavior and blood half-life of SPIOs.Methods: Eleven different SPIOs were synthesized for this study. In the first set (a, seven carboxydextran (CDX-coated SPIOs of different sizes (19–86 nm were obtained by fractionating a broadly size-distributed CDX–SPIO. The second set (b contained three SPIOs of identical size (50 nm that were stabilized with different coating materials, polyacrylic acid (PAA, polyethylene glycol, and starch. Furthermore, small PAA–SPIOs (20 nm were synthesized to gain a global insight into the effects of particle size vs coating characteristics. Saturation magnetization and proton relaxivity were determined to represent the magnetic and imaging properties. The blood half-life was analyzed in rats using MRI, time-domain nuclear magnetic resonance, and inductively coupled plasma optical emission spectrometry.Results: By changing the particle size without modifying any other parameters, the relaxivity r2 increased with increasing mean particle diameter. However, the blood half-life was shorter for larger particles. The effect of the coating material on magnetic properties was less pronounced, but it had a strong influence on blood kinetics depending on the

  12. The effect of liver esterases and temperature on remifentanil degradation in vitro.

    Piazza, Ornella; Cascone, Sara; Sessa, Linda; De Robertis, Edoardo; Lamberti, Gaetano


    Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients. The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed. Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.

  13. Effects of chronic alternating cadmium exposure on the episodic secretion of prolactin in male rats

    Esquifino, A.I. [Madrid Univ. (Spain). Facultad de Medicina Complutense; Marquez, N.; Alvarez-Demanuel, E.; Lafuente, A. [Vigo Univ., Orense (Spain). Lab. de Toxicologia


    Cadmium increases or decreases prolactin secretion depending on the dose and duration of the exposure to the metal. However, whether there are cadmium effects on the episodic prolactin secretion is less well known. This study was undertaken to address whether chronic alternating exposure to two different doses of cadmium affects the episodic pattern of prolactin and to what extent the effects of cadmium are age-dependent. Male rats were treated s.c. with cadmium chloride (0.5 or 1.0 mg/kg) from day 30 to 60, or from day 60 to 90 of age, with alteration of the doses every 4 days, starting with the smaller dose. Controls received vehicle every 4 days. The last dose of cadmium was given 48 h prior to the pulsatility study. Prolactin secretion in the 4 experimental groups studied was episodic and changed significantly after cadmium exposure. Cadmium administration from day 30 to 60 of life significantly decreased the mean half-life of prolactin. On the other hand, when administered from day 60 to 90 cadmium significantly decreased the mean as well as serum prolactin levels and the absolute amplitude of the prolactin pulses, their duration, the relative amplitude or the mean half-life of the hormone. The frequency of prolactin peaks was not changed by cadmium administration. The results indicate that low intermittent doses of cadmium chronically administered change the episodic secretion pattern of prolactin in rats. The effects of cadmium on prolactin secretion were age dependent. (orig.)

  14. Effect of oxymatrine HSPC liposomes on improving bioavailability, liver target distribution and hepatoprotective activity of oxymatrine.

    Liu, Meifeng; Jin, Sha; Yan, Hao; Du, Song


    Oxymatrine (OMT) and matrine (MT) are two naturally occurring alkaloids, both of them provide anti-hepatitis effects. However OMT effect was heavily limited due to its low bioavailability, short half-life and whole body distribution. Herein, we investigated hydrogenated soybean phosphatidylcholine (HSPC) liposomes made by pH gradient active loading to understand the improved hepatoprotective effect mechanisms. Pharmacokinetics researches demonstrated the half-life time of OMT HSPC liposomes was 17.10h in mice. Compared with OMT solution, AUC (0-8) of OMT and MRT (0-8) of MT had been increased 11.8 fold and 14.3 fold in HSPC liposomes. Moreover, tissue distribution revealed the relative AUCs of total alkaloids in liver of OMT HSPC liposomes was as 4.18 times as that of OMT solution. Our data suggested that pathological topical necrosis and mild vacuolar degeneration of liver progressively returned to normal, and serum level of alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) were significantly reduced after treating with OMT HSPC liposomes in acute liver injury mice induced by CCl4. Pharmacokinetics, biodistribution and pathological researches manifested that HSPC liposomes served as an ideal and potential oxymatrine liver target carrier to prolong OMT retention time and maintain high therapeutically level in liver. Copyright © 2017. Published by Elsevier B.V.

  15. Effects of gamma irradiation on microbial load and quality characteristics of veal.

    Rahimi, Ebrahim; Faghihi, Reza; Baradaran-Ghahfarokhi, Milad; Alavaian-Ghavanini, Ali; Baradaran-Ghahfarokhi, Hamid Reza; Siavashpour, Zahra; Farshadi, Afrouz; Rafie, Farzad


    Veal is a rich nutrient medium that provides a suitable environment for proliferation of veal spoiling microorganisms and common food-borne pathogens. In this study, the effects of irradiation on the veal microbiological quality and half life of minced beef during chilled storage was investigated. Twenty samples of minced veal were irradiated with doses of 2, 5, 7, and 10 kGy (Cobalt-60, gamma cell 220) and evaluated for their microbiological quality up to 10 days. The results showed that gamma irradiation reduced the number of microorganisms in all the irradiated minced veal samples, with 2, 5, 7, and 10 kGy (P coliformes between untreated and irradiated samples (P < 0.05). While, Staphylococcus aureus could not be detected in the irradiated samples with doses of 7 and 10 kGy. These results indicated that irradiation could be employed as an effective mean to inactivate common food-borne pathogens namely S. aureus and increases the half life of veal.

  16. Waste recombinant DNA: effectiveness of thermo-treatment to manage potential gene pollution.

    Fu, Xiaohua; Li, Mengnan; Zheng, Guanghong; Le, Yiquan; Wang, Lei


    Heating at 100 degrees C for 5-10 min is a common method for treating wastewater containing recombinant DNA in many bio-laboratories in China. In this experiment, plasmid pET-28b was used to investigate decay efficiency of waste recombinant DNA during thermo-treatment. The results showed that the decay half-life of the plasmid was 2.7-4.0 min during the thermo-treatment, and even heating for 30 min the plasmids still retained some transforming activity. Low pH promoted the decay of recombinant DNA, but NaCl, bovine serum albumin and EDTA, which existed in the most wastewater from bio-laboratories, protected DNA from degradation. Thus, the decay half-life of plasmid DNA may be longer than 2.7-4.0 min practically. These results suggest that the effectiveness of heating at 100 degrees C for treating waste recombinant DNA is low and a gene pollution risk remains when those thermo-treated recombinant DNAs are discharged into the environment. Therefore other simple and effective methods should be developed.

  17. Interaction-Free Effects Between Distant Atoms

    Aharonov, Yakir; Elitzur, Avshalom C; Smolin, Lee


    A gedankenexperiment is presented where an excited and a ground-state atom are positioned such that, within the former's half-life time, they exchange a photon with 50% probability. A measurement of their energy state will therefore indicate in 50% of the cases that no photon was exchanged. Yet other measurements would reveal that, by the mere possibility of exchange, the two atoms become entangled. Consequently, the "no exchange" result, apparently precluding entanglement, is non-locally established between the atoms by this very entanglement. When densely repeated several times, this result gives rise to the Quantum Zeno effect as well, again exerted between distant atoms without photon exchange. We discuss these experiments as variants of IFM, now generalized for both spatial and temporal uncertainties. We next employ weak measurements for a sharper and simpler elucidation of the paradox. Interpretational issues are discussed in the conclusion, and a resolution is offered within the Two-State Vector Formal...

  18. Factors Effecting the Fate and Transport of CL-20 in the Vadose Zone and Groundwater


    reactant half-life (h) half-life (h) maximum (%) half-life (h) half-life (h) microbe Shewanella putrefaciens , CN32, 1E7 533 + water Shewanella ... putrefaciens , CN32, 4.6E7 114 1500 31%, 715 h Shewanella putrefaciens , CN32, 1E8 45.6 1100 36%, 715 h Shewanella putrefaciens , CN32, 5.7E8 881 40%, 715 degraded/mineralized in reducing systems). Reducing systems may differ; an iron degrading isolate, Shewanella putrefaciens (CN32) can readily

  19. Evaluation of antioxidative effects of sesamin on the in vivo hepatic reducing abilities by a radiofrequency ESR method.

    Tada, Mika; Ono, Yoshiko; Nakai, Masaaki; Harada, Masami; Shibata, Hiroshi; Kiso, Yoshinobu; Ogata, Tateaki


    Antioxidative effects of sesamin (a mixture of sesamin and episesamin) were evaluated in the liver, kidney and inferior vena cava of living rats using a radiofrequency ESR method. TEMPOL, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl, was used as an in vivo redox probe, the half-life of which is believed to be correlated with the antioxidant status. The oral administration of sesamin (250 mg/kg rat weight) 3 h before ESR measurements shortened the half-life of TEMPOL in the liver by 10 - 15% as compared with the controls, but did not affect the other organs. This effect was maintained for at least 3 h after the administration, and then disappeared at 24 h, corresponding to the results of our preliminary pharmacokinetic studies. Changes in the reducing ability were observed only in the hepatic sites of the sesamin-treated rats. These findings suggest that sesamin exhibits effective antioxidant activity in the liver via modulation of the intracellular redox status related to TEMPOL reduction.

  20. Dose-Response Analysis of the Effect of Carbidopa-Levodopa Extended-Release Capsules (IPX066) in Levodopa-Naive Patients With Parkinson Disease.

    Mao, Zhongping Lily; Modi, Nishit B


    Parkinson disease is an age-related disorder of the central nervous system principally due to loss of dopamine-producing cells in the midbrain. Levodopa, in combination with carbidopa, is widely regarded as an effective treatment for the symptoms of Parkinson disease. A dose-response relationship is established for carbidopa-levodopa extended-release capsules (IPX066) in levodopa-naive Parkinson disease patients using a disease progression model. Unified Parkinson Disease Rating Scale (UPDRS) part II plus part III scores from 171 North American patients treated with placebo or IPX066 for approximately 30 weeks from a double-blind, parallel-group, dose-ranging study were used to develop the pharmacodynamic model. The model comprised 3 components: a linear function describing disease progression, a component describing placebo (or nonlevodopa) effects, and a component to describe the effect of levodopa. Natural disease progression in early Parkinson disease as measured by UPDRS was 11.6 units/year and faster in patients with more severe disease (Hoehn-Yahr stage 3). Maximum placebo/nonlevodopa response was 23.0% of baseline UPDRS. Maximum levodopa effect from IPX066 was 76.7% of baseline UPDRS, and the ED50 was 450 mg levodopa. Equilibration half-life for the effect compartment was 62.8 days. Increasing age increased and being female decreased equilibration half-life. The quantitative model allowed description of the entire time course of response to clinical trial intervention.

  1. Degradation of tricyclazole: Effect of moisture, soil type, elevated carbon dioxide and Blue Green Algae (BGA).

    Kumar, Naveen; Mukherjee, Irani; Sarkar, Bipasa; Paul, Ranjit Kumar


    Pesticide persistence and degradation in soil are influenced by factors like soil characteristics, light, moisture etc. Persistence of tricyclazole was studied under different soil moisture regimes viz., dry, field capacity and submerged in two different soil types viz., Inceptisol and Ultisol from Delhi and Karnataka, respectively. Tricyclazole dissipated faster in submerged (t1/2 160.22-177.05d) followed by field capacity (t1/2 167.17-188.07d) and dry (t1/2 300.91-334.35d) in both the soil types. Half-life of tricyclazole in Delhi field capacity soil amended with Blue Green Algae (BGA), was 150.5d as compared to 167.1d in unamended soil. In Karnataka soil amended with BGA the half-lives were 177.0d compared to 188.0d in unamended soil, indicating that BGA amendment enhanced the rate of dissipation of in both the selected soils. Tricyclazole was found to be stable in water over a pH range of 3-9, the half life in paddy field was 60.20d and 5.47d in paddy soil and paddy water, respectively. Statistical analysis and Duncan's Multiple Range Test (DMRT) revealed significant effect of moisture regime, organic matter and atmospheric CO2 level on dissipation of tricyclazole from soil and pH of water (at 95% confidence level p<0.0001). Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Effect of elevated CO2 on chlorpyriphos degradation and soil microbial activities in tropical rice soil.

    Adak, Totan; Munda, Sushmita; Kumar, Upendra; Berliner, J; Pokhare, Somnath S; Jambhulkar, N N; Jena, M


    Impact of elevated CO2 on chlorpyriphos degradation, microbial biomass carbon, and enzymatic activities in rice soil was investigated. Rice (variety Naveen, Indica type) was grown under four conditions, namely, chambered control, elevated CO2 (550 ppm), elevated CO2 (700 ppm) in open-top chambers and open field. Chlorpyriphos was sprayed at 500 g a.i. ha(-1) at maximum tillering stage. Chlorpyriphos degraded rapidly from rice soils, and 88.4% of initially applied chlorpyriphos was lost from the rice soil maintained under elevated CO2 (700 ppm) by day 5 of spray, whereas the loss was 80.7% from open field rice soil. Half-life values of chlorpyriphos under different conditions ranged from 2.4 to 1.7 days with minimum half-life recorded with two elevated CO2 treatments. Increased CO2 concentration led to increase in temperature (1.2 to 1.8 °C) that played a critical role in chlorpyriphos persistence. Microbial biomass carbon and soil enzymatic activities specifically, dehydrogenase, fluorescien diacetate hydrolase, urease, acid phosphatase, and alkaline phosphatase responded positively to elevated CO2 concentrations. Generally, the enzyme activities were highly correlated with each other. Irrespective of the level of CO2, short-term negative influence of chlorpyriphos was observed on soil enzymes till day 7 of spray. Knowledge obtained from this study highlights that the elevated CO2 may negatively influence persistence of pesticide but will have positive effects on soil enzyme activities.

  3. Effects of ketoconazole or rifampin on the pharmacokinetics of tivozanib hydrochloride, a vascular endothelial growth factor receptor tyrosine kinase inhibitor.

    Cotreau, Monette M; Siebers, Nicholas M; Miller, James; Strahs, Andrew L; Slichenmyer, William


    The vascular endothelial growth factor (VEGF) pathway is associated with the promotion of endothelial cell proliferation, migration, and survival necessary for angiogenesis. VEGF and its three receptor isoforms are often overexpressed in many human solid tumors. Tivozanib is a potent, selective inhibitor of VEGF receptors 1, 2, and 3, with a long half-life. The purpose of these studies was to evaluate the effect of ketoconazole, a potent inhibitor of CYP3A4, and rifampin, a potent inducer of CYP3A4, on the pharmacokinetics of tivozanib. Two phase I, open-label, 2-period, single-sequence studies evaluated the effect of steady-state ketoconazole (NCT01363778) or rifampin (NCT01363804) on the pharmacokinetic profile, safety, and tolerability of a single oral 1.5-mg dose of tivozanib. Tivozanib was well tolerated in both studies. Steady-state ketoconazole did not cause a clinically significant change in the pharmacokinetics of a single dose of tivozanib; therefore, dosing of tivozanib with a CYP3A4 pathway inhibitor should not cause a clinically significant change in serum tivozanib levels. However, coadministration of tivozanib with rifampin caused a significant decrease in the area under the curve from 0 to infinity and half-life and an increase in clearance of tivozanib, which suggest increased clearance via the enhanced CYP3A4-mediated metabolism of tivozanib.

  4. The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes.

    William P Clafshenkel

    Full Text Available Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP, may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidylsuberate (BS3. A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system.

  5. Effect of Selected Modeling Assumptions on Subsurface Radionuclide Transport Projections for the Potential Environmental Management Disposal Facility at Oak Ridge, Tennessee

    Painter, Scott L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Environmental Sciences Division


    The Department of Energy’s Office of Environmental Management recently revised a Remedial Investigation/ Feasibility Study (RI/FS) that included an analysis of subsurface radionuclide transport at a potential new Environmental Management Disposal Facility (EMDF) in East Bear Creek Valley near Oak Ridge, Tennessee. The effect of three simplifying assumptions used in the RI/FS analyses are investigated using the same subsurface pathway conceptualization but with more flexible modeling tools. Neglect of vadose zone dispersion was found to be conservative or non-conservative, depending on the retarded travel time and the half-life. For a given equilibrium distribution coefficient, a relatively narrow range of half-life was identified for which neglect of vadose zone transport is non-conservative and radionuclide discharge into surface water is non-negligible. However, there are two additional conservative simplifications in the reference case that compensate for the non-conservative effect of neglecting vadose zone dispersion: the use of a steady infiltration rate and vadose zone velocity, and the way equilibrium sorption is used to represent transport in the fractured material of the saturated aquifer. With more realistic representations of all three processes, the RI/FS reference case was found to either provide a reasonably good approximation to the peak concentration or was significantly conservative (pessimistic) for all parameter combinations considered.

  6. Bioprocess and biotecnology: effect of xylanase from Aspergillus niger and Aspergillus flavus on pulp biobleaching and enzyme production using agroindustrial residues as substract.

    de Alencar Guimaraes, Nelciele Cavalieri; Sorgatto, Michele; Peixoto-Nogueira, Simone de Carvalho; Betini, Jorge Henrique Almeida; Zanoelo, Fabiana Fonseca; Marques, Maria Rita; de Moraes Polizeli, Maria de Lourdes Teixeira; Giannesi, Giovana C


    This study compares two xylanases produced by filamentous fungi such as A. niger and A. flavus using agroindustrial residues as substract and evaluated the effect of these enzymes on cellulose pulp biobleaching process. Wheat bran was the best carbon source for xylanase production by A. niger and A. flavus. The production of xylanase was 18 and 21% higher on wheat bran when we compare the xylanase production with xylan. At 50°C, the xylanase of A. niger retained over 85% activity with 2 h of incubation, and A. flavus had a half-life of more than 75 minutes. At 55°C, the xylanase produced by A. niger showed more stable than from A. flavus showing a half-life of more than 45 minutes. The xylanase activity of A. niger and A. flavus were somehow protected in the presence of glycerol 5% when compared to the control (without additives). On the biobleaching assay it was observed that the xylanase from A. flavus was more effective in comparison to A. niger. The kappa efficiency corresponded to 36.32 and 25.93, respectively. That is important to emphasize that the cellulase activity was either analyzed and significant levels were not detected, which explain why the viscosity was not significantly modified.

  7. Effective liquid drop description for alpha decay of atomic nuclei

    Tavares, O.A.P.; Duarte, S.B. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Rodriguez, O.; Guzman, F. [Instituto Superior de Ciencia y Tecnologia Nuclear (ISCTN), La Habana (Cuba); Goncalves, M. [Instituto de Radioprotecao e Dosimetria (IRD), Rio de Janeiro, RJ (Brazil); Garcia, F. [Sao Paulo Univ., SP (Brazil). Inst. de Fisica


    Alpha decay half-lives are presented in the framework of an effective liquid drop model for different combination of mass transfer descriptions and inertia coefficients. Calculated half-life-values for ground-state to ground-state favoured alpha transitions are compared with available, updated experimental data. Results have shown that the present model is very suitable to treat the alpha decay process on equal foot as cluster radioactivity and cold fission processes. Better agreement with the data is found when the sub-set of even-even alpha emitters are considered in the calculation. (author) 44 refs., 5 figs., 3 tabs.; e-mail: telo at

  8. Veterinary Antibiotic Effects on Atrazine Degradation and Soil Microorganisms.

    Nordenholt, Rebecca M; Goyne, Keith W; Kremer, Robert J; Lin, Chung-Ho; Lerch, Robert N; Veum, Kristen S


    Veterinary antibiotics (VAs) in manure applied to agricultural lands may change agrichemical degradation by altering soil microbial community structure or function. The objectives of this study were to investigate the influence of two VAs, sulfamethazine (SMZ) and oxytetracycline (OTC), on atrazine (ATZ) degradation, soil microbial enzymatic activity, and phospholipid fatty acid (PLFA) markers. Sandy loam soil with and without 5% swine manure (w/w) was amended with 0 or 500 μg kgC radiolabeled ATZ and with 0, 100, or 1000 μg kg SMZ or OTC and incubated at 25°C in the dark for 96 d. The half-life of ATZ was not significantly affected by VA treatment in the presence or absence of manure; however, the VAs significantly ( degradation by 22%, reduced ATZ mineralization by 50%, and increased the half-life of ATZ by >10 d. The VAs had limited adverse effects on the microbial enzymes β-glucosidase and dehydrogenase in soils with and without manure. In contrast, manure application stimulated dehydrogenase activity and altered chlorinated ATZ metabolite profiles. Concentrations of PLFA markers were reduced by additions of ATZ, manure, OTC, and SMZ; adverse additive effects of combined treatments were noted for arbuscular mycorrhizal fungi and actinobacteria. In this work, the VAs did not influence persistence of the ATZ parent compound or chlorinated ATZ metabolite formation and degradation. However, reduced CO evolved from VA-treated soil suggests an inhibition to the degradation of other ATZ metabolites due to an altered soil microbial community structure.

  9. Environmental fate and effects of nicotine released during cigarette production.

    Seckar, Joel A; Stavanja, Mari S; Harp, Paul R; Yi, Yongsheng; Garner, Charles D; Doi, Jon


    A variety of test methods were used to study the gradation, bioaccumulation, and toxicity of nicotine. Studies included determination of the octanol-water partition coefficient, conversion to CO2 in soil and activated sludge, and evaluation of the effects on microbiological and algal inhibition as well as plant germination and root elongation. The partitioning of nicotine between octanol and water indicated that nicotine will not bioaccumulate regardless of the pH of the medium. The aqueous and soil-based biodegradation studies indicated that nicotine is readily biodegradable in both types of media. The microbiological inhibition and aquatic and terrestrial toxicity tests indicated that nicotine has low toxicity. The U.S. Environmental Protection Agency Persistence, Bioaccumulation, and Toxicity Profiler model, based on the structure of nicotine and the predictive rates of hydroxyl radical and ozone reactions, estimated an atmospheric half-life of less than 5.0 h. Using this value in the Canadian Environmental Modeling Center level III model, the half-life of nicotine was estimated as 3.0 d in water and 0.5 d in soil. This model also estimated nicotine discharge into the environment; nicotine would be expected to be found predominantly in water (93%), followed by soil (4%), air (3%), and sediment (0.4%). Using the estimated nicotine concentrations in water, soil, and sediment and the proper median effective concentrations derived from the algal growth, biomass inhibition, and buttercrunch lettuce (Lactuca sativa) seed germination and root elongation studies, hazard quotients of between 10(-7) and 10(-8) were calculated, providing further support for the conclusion that the potential for nicotine toxicity to aquatic and terrestrial species in the environment is extremely low.

  10. Life is a journey: source-path-goal structure in the videogames "Half-Life 2", "Heavy Rain", and "Grim Fandango"

    Kromhout, R.; Forceville, C.


    The debate between narrativists and ludologists has long enlivened discussions among game theorists. Should videogames be seen as an offshoot of (film) stories, and thus be studied primarily from the perspective of narratology? Or do they represent a truly different phenomenon, and thus require an a

  11. Influência dos sucos de frutas sobre a biodisponibilidade e meia-vida dos medicamentos = Fruit juices influence in the bioavailability and half-life of drugs

    Salvi, Rosane Maria


    Conclusão: O estudo evidenciou que interações entre sucos de laranja e toranja consistem nas ocorrências mais comumente citadas, muitas vezes responsáveis por variações sobre a biodisponibilidade e meia-vida de fármacos o que, em última instância, determina variações na resposta terapêutica

  12. From J. J. Thomson to FAIR, what do we learn from Large-Scale Mass and Half-Life Measurements of Bare and Few-Electron Ions?

    Münzenberg, Gottfried; Geissel, Hans; Litvinov, Yuri A.


    This contribution is based on the combination of the talks: "What can we learn from large-scale mass measurements," "Present and future experiments with stored exotic nuclei at relativistic energies," and "Beta decay of highly-charged ions." Studying the nuclear mass surface gives information on the evolution of nuclear structure such as nuclear shells, the onset of deformation and the drip-lines. Previously, most of the masses far-off stability has been obtained from decay data. Modern methods allow direct mass measurements. They are much more sensitive, down to single atoms, access short-lived species and have high accuracy. Large-scale explorations of the nuclear mass surface are ideally performed with the combination of the in-flight FRagment Separator FRS and the Experimental Storage Ring ESR. After a brief historic introduction selected examples such as the evolution of shell closures far-off stability and the proton-neutron interaction will be discussed in the framework of our data. Recently, the experiments have been extended and led to the discovery of new heavy neutron-rich isotopes along with their mass and lifetime measurements. Storage rings applied at relativistic energies are a unique tool to study the radioactive decay of bare or few-electron atomic nuclei. New features observed with the analysis of stored circulating mother and daughter ions including oscillations in the decay curves of hydrogen-like nuclei will be addressed. Future experiments with NUSTAR at FAIR will further extend our knowledge to the borderlines of nuclear existence.

  13. Measurement of the double-β decay half-life and search for the neutrinoless double-β decay of 48Ca with the NEMO-3 detector

    Waters, David; Vilela, Cristóvão; NEMO-3 collaboration


    Neutrinoless double-β decay is a powerful probe of lepton number violating processes that may arise from Majorana terms in neutrino masses, or from supersymmetric, left-right symmetric, and other extensions of the Standard Model. Of the candidate isotopes for the observation of this process, 48Ca has the highest Qββ -value, resulting in decays with energies significantly above most naturally occurring backgrounds. The nucleus also lends itself to precise matrix element calculations within the nuclear shell model. We present the world’s best measurement of the two-neutrino double-β decay of 48Ca, obtained by the NEMO-3 collaboration using 5.25 yr of data recorded with a 6.99 g sample of isotope, yielding ≈ 150 events with a signal to background ratio larger than 3. Neutrinoless modes of double-β decay are also investigated, with no evidence of new physics. Furthermore, these results indicate that two-neutrino double-β decay would be the main source of background for similar future searches using 48Ca with significantly larger exposures.

  14. 医学期刊被引半衰期分析%An Analysis on Medical Journal Cited Half-life

    戴丽琼; 毛文明; 姜美萍



  15. Life is a journey: source-path-goal structure in the videogames "Half-Life 2", "Heavy Rain", and "Grim Fandango"

    Kromhout, R.; Forceville, C.


    The debate between narrativists and ludologists has long enlivened discussions among game theorists. Should videogames be seen as an offshoot of (film) stories, and thus be studied primarily from the perspective of narratology? Or do they represent a truly different phenomenon, and thus require an

  16. Glucagon-like Peptide 1 Conjugated to Recombinant Human Serum Albumin Variants with Modified Neonatal Fc Receptor Binding Properties. Impact on Molecular Structure and Half-Life

    Bukrinski, Jens T.; Sønderby, Pernille; Antunes, Filipa


    cells of blood vessels, which rescues circulating HSA from lysosomal degradation. We have conjugated GLP-1 to C34 of native sequence recombinant HSA (rHSA) and two rHSA variants; one with increased and one with decreased binding affinity to hFcRn. We have investigated the impact of conjugation on Fc......Rn binding affinities, GLP-1 potency and pharmacokinetics, combined with the solution structure of the rHSA variants and GLP-1 albumin conjugates. The solution structures, determined by small angle X-ray scattering, show the GLP-1 pointing away from the surface of rHSA. Combining the solution structures...... with the available structural information on the FcRn and GLP-1 receptor (GLP-1R) obtained from X-ray crystallography, we can explain the observed in-vitro and in-vivo behaviour. We conclude that the conjugation of GLP-1 to rHSA does not affect the interaction between rHSA and FcRn, while the observed decrease...

  17. Half-life Model: the Scale of Kaizen%半生命周期--持续改进的标尺

    郭春明; 韩之俊



  18. Investigation of the Efficiencies of Bioaerosol Samplers for Collecting Aerosolized Bacteria Using a Fluorescent Tracer. II: Sampling Efficiency and Half-Life Time

    Zhao, Y.; Aarnink, A.J.A.; Doornenbal, P.; Huynh, T.T.T.; Groot Koerkamp, P.W.G.; Landman, W.J.M.; Jong, de M.C.M.


    Using uranine as a physical tracer, this study assessed the sampling efficiencies of four bioaerosol samplers (Andersen 6-stage impactor, all glass impinger “AGI-30,” OMNI-3000, and Airport MD8 with gelatin filter) for collecting Gram-positive bacteria (Enterococcus faecalis), Gram-negative bacteria

  19. Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts.

    Thong T Nguyen

    Full Text Available Genetic variation in gene expression makes an important contribution to phenotypic variation and susceptibility to disease. Recently, a subset of cis-acting expression quantitative loci (eQTLs has been found to result from polymorphisms that affect RNA stability. Here we carried out a search for trans-acting variants that influence RNA stability. We first demonstrate that differences in the activity of trans-acting factors that stabilize RNA can be detected by comparing the expression levels of long-lived (stable and short-lived (unstable transcripts in high-throughput gene expression experiments. Using gene expression microarray data generated from eight HapMap3 populations, we calculated the relative expression ranks of long-lived transcripts versus short-lived transcripts in each sample. Treating this as a quantitative trait, we applied genome-wide association and identified a single nucleotide polymorphism (SNP, rs6137010, on chromosome 20p13 with which it is strongly associated in two Asian populations (p = 4×10(-10 in CHB - Han Chinese from Beijing; p = 1×10(-4 in JPT - Japanese from Tokyo. This SNP is a cis-eQTL for SNRPB in CHB and JPT but not in the other six HapMap3 populations. SNRPB is a core component of the spliceosome, and has previously been shown to affect the expression of many RNA processing factors. We propose that a cis-eQTL of SNRPB may be directly responsible for inter-individual variation in relative expression of long-lived versus short-lived transcript in Asian populations. In support of this hypothesis, knockdown of SNRPB results in a significant reduction in the relative expression of long-lived versus short-lived transcripts. Samples with higher relative expression of long-lived transcripts also had higher relative expression of coding compared to non-coding RNA and of RNA from housekeeping compared to non-housekeeping genes, due to the lower decay rates of coding RNAs, particularly those that perform housekeeping functions, compared to non-coding RNAs.

  20. Half-life systematics across the N=126 shell closure: role of first-forbidden transitions in the β decay of heavy neutron-rich nuclei.

    Morales, A I; Benlliure, J; Kurtukián-Nieto, T; Schmidt, K-H; Verma, S; Regan, P H; Podolyák, Z; Górska, M; Pietri, S; Kumar, R; Casarejos, E; Al-Dahan, N; Algora, A; Alkhomashi, N; Álvarez-Pol, H; Benzoni, G; Blazhev, A; Boutachkov, P; Bruce, A M; Cáceres, L S; Cullen, I J; Denis Bacelar, A M; Doornenbal, P; Estévez-Aguado, M E; Farrelly, G; Fujita, Y; Garnsworthy, A B; Gelletly, W; Gerl, J; Grebosz, J; Hoischen, R; Kojouharov, I; Kurz, N; Lalkovski, S; Liu, Z; Mihai, C; Molina, F; Mücher, D; Rubio, B; Shaffner, H; Steer, S J; Tamii, A; Tashenov, S; Valiente-Dobón, J J; Walker, P M; Wollersheim, H J; Woods, P J


    This Letter reports on a systematic study of β-decay half-lives of neutron-rich nuclei around doubly magic (208)Pb. The lifetimes of the 126-neutron shell isotone (204)Pt and the neighboring (200-202)Ir, (203)Pt, (204)Au are presented together with other 19 half-lives measured during the "stopped beam" campaign of the rare isotope investigations at GSI collaboration. The results constrain the main nuclear theories used in calculations of r-process nucleosynthesis. Predictions based on a statistical macroscopic description of the first-forbidden β strength reveal significant deviations for most of the nuclei with Nforbidden transitions reproduce more satisfactorily the trend in the measured half-lives for the nuclei in this region, where the r-process pathway passes through during β decay back to stability.

  1. Life is a journey: source-path-goal structure in the videogames "Half-Life 2", "Heavy Rain", and "Grim Fandango"

    Kromhout, R.; Forceville, C.


    The debate between narrativists and ludologists has long enlivened discussions among game theorists. Should videogames be seen as an offshoot of (film) stories, and thus be studied primarily from the perspective of narratology? Or do they represent a truly different phenomenon, and thus require an a

  2. Biological degradation and microbial function effect of norfloxacin in a soil under different conditions.

    Yang, Ji-Feng; Ying, Guang-Guo; Liu, Shan; Zhou, Li-Jun; Zhao, Jian-Liang; Tao, Ran; Peng, Ping-An


    This paper investigated the degradation kinetics of norfloxacin in a soil, and its effects on soil respiration and nitrogen transformation under different conditions. Compared to the sterile control, the degradation rates of norfloxacin in the non-sterile soil were greatly enhanced, suggesting that microorganisms played a major role in the degradation. Accelerated degradation for norfloxacin in the soil was observed with decreasing concentrations (30 mg/kg to 5 mg/kg) with its half-life decreasing from 62 days to 31 days. Amending swine manure into the soil and increasing the soil moisture level enhanced the biological degradation of norfloxacin. No obvious inhibition of norfloxacin on soil respiration was observed in the soil, while only slight effect on nitrogen transformation was found. The results suggested that norfloxacin at the reported environmental concentrations (<100 mg/kg) would have little effect on microbial activity and functions in the soils.

  3. Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

    Bourin, M; Hascoet, M; Mansouri, B; Colombel, M C; Bradwejn, J


    The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans. PMID:1637802

  4. Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

    Bourin, M; Hascoet, M; Mansouri, B; Colombel, M C; Bradwejn, J


    The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans.

  5. Involvement of glucagon-like peptide-1 in the glucose-lowering effect of metformin

    Bahne, Emilie; Hansen, Morten; Brønden, Andreas;


    Metformin is an oral antihyperglycaemic drug used in the first-line treatment of type 2 diabetes. Metformin's classic and most well-known blood glucose-lowering mechanisms include reduction of hepatic gluconeogenesis and increased peripheral insulin sensitivity. Interestingly, intravenously...... administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin's glucose-lowering effect in patients with type 2 diabetes. The mechanisms behind metformin......-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1. Also, it has been suggested that metformin may potentiate the glucose-lowering effects of GLP-1 by increasing target...

  6. Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer

    Jasem Al Shemaili


    Full Text Available The frondosides are triterpenoid glycosides from the Atlantic sea cucumber Cucumaria frondosa. Frondoside A inhibits growth, invasion, metastases and angiogenesis and induces apoptosis in diverse cancer types, including pancreatic cancer. We compared the growth inhibitory effects of three frondosides and their aglycone and related this to the pharmocokinetics and route of administration. Frondoside A potently inhibited growth of pancreatic cancer cells with an EC50 of ~1 µM. Frondoside B was less potent (EC50 ~2.5 µM. Frondoside C and the aglycone had no effect. At 100 µg/kg, frondoside A administered to CD2F1 mice as an i.v. bolus, the Cpmax was 129 nM, Cltb was 6.35 mL/min/m2, and half-life was 510 min. With i.p. administration the Cpmax was 18.3 nM, Cltb was 127 mL/min/m2 and half-life was 840 min. Oral dosing was ineffective. Frondoside A (100 µg/kg/day i.p. markedly inhibited growth cancer xenografts in nude mice. The same dose delivered by oral gavage had no effect. No evidence of acute toxicity was seen with frondoside A. Frondoside A is more potent inhibitor of cancer growth than other frondosides. The glycoside component is essential for bioactivity. Frondoside A is only effective when administered systemically. Based on the current and previous studies, frondoside A appears safe and may be valuable in the treatment of cancer.

  7. Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer

    Y. Sobita Devi


    Full Text Available Purpose: The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation withlocal/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate(HDR brachytherapy (BT source is reduced to single, double and triple half life in relation to original strength of10 Ci (~ 4.081 cGy x m2 x h–1. Material and methods: A retrospective study was carried out on 52 cervical cancer patients with stage II and IIItreated with fractionated HDR-BT following external beam radiation therapy (EBRT. International Commission onRadiation Units and Measurement (ICRU points were defined according to ICRU Report 38, using two orthogonal radiographimages taken by Simulator (Simulix HQ. Biologically effective dose (BED was calculated at point A for diffe -rent Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed. Result: The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervicalcancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction ofsource strength, respectively. The probabilities of disease recurrence (local/loco-regional within 26 months are expectedas 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h–1, respectively.The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively. Conclusions: This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 sourcestrength shows reduction in disease free survival according to the increase in treatment time duration per fraction.The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical

  8. Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers.

    Lei, H-P; Yu, X-Y; Xie, H-T; Li, H-H; Fan, L; Dai, L-L; Chen, Y; Zhou, H-H


    The objective of this study was to investigate the effects of continuous St. John's wort administration on single-dose pharmacokinetics of bupropion, a substrate of cytochrome P450 (CYP) 2B6, in healthy Chinese volunteers. Eighteen unrelated healthy male subjects participated in this study. The single-dose pharmacokinetics of bupropion and hydroxybupropion were determined before (control) and after a long-term period of St. John's wort intake (325 mg, three times a day for 14 days). Plasma concentrations of bupropion and hydroxybupropion were determined before and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60 and 72 h after dosing. St. John's wort treatment decreased the area under the concentration versus time curve extrapolated to infinity of bupropion in healthy volunteers from 1.4 microg.h ml(-1) (95% confidence interval [CI] = 1.2-1.6 microg.h ml(-1)) after bupropion alone to 1.2 microg.h ml(-1) (95% CI = 1.1-1.3 microg.h ml(-1)) during St. John's wort treatment. St. John's wort treatment increased the oral clearance of bupropion from 108.3 l h(-1) (95% CI = 95.4-123.0 l h(-1)) to 130.0 l h(-1) (95% CI = 118.4-142.7 l h(-1)). No change in the time to peak concentration (t(max)) and the blood elimination half-life (t(1/2)) of bupropion was observed between the control and St. John's wort-treated phases. However, the half-life of hydroxybupropion between two phases had a significant difference by a Student's t test after logarithmic transformation. St. John's wort treatment decreased the half-life of hydroxybupropion from 26.7 h (95% CI = 23.8-29.9 h) to 24.4 h (95% CI = 21.9-27.3 h). St. John's wort decreased, to a statistically significant extent, the plasma concentrations of bupropion, probably mainly by increasing the clearance of bupropion.

  9. The effect of immobilization stress on the pharmacokinetics of omeprazole in rats.

    Watanabe K


    Full Text Available The effects of immobilization stress on the pharmacokinetics of omeprazole were studied in rats. The immobilization stress for 30 or 60 min immediately after oral administration of the drug caused an increase in the time to reach the maximum concentration. However, such stress did not alter the area under the plasma concentration-time curve (AUC. When administered intravenously, the half-life during the elimination phase was significantly prolonged by 30 min of immobilization stress, but the AUC value remained unchanged. The intestinal propulsive activity was significantly decreased by immobilization stress. These findings suggest that immobilization stress reduces gastrointestinal motility. A resulting delay during the absorption phase of omeprazole occurs, although the degree of influence on overall pharmacokinetics is relatively insignificant.

  10. Effect of polymers on the retention and aging of enzyme on bioactive papers.

    Khan, Mohidus Samad; Haniffa, Sharon B M; Slater, Alison; Garnier, Gil


    The effect of polymer on the retention and the thermal stability of bioactive enzymatic papers was measured using a colorimetric technique quantifying the intensity of the enzyme-substrate product complex. Alkaline phosphatase (ALP) was used as model enzyme. Three water soluble polymers: a cationic polyacrylamide (CPAM), an anionic polyacrylic acid (PAA) and a neutral polyethylene oxide (PEO) were selected as retention aids. The model polymers increased the enzyme adsorption on paper by around 50% and prevented enzyme desorption upon rewetting of the papers. The thermal deactivation of ALP retained on paper with polymers follows two sequential first order reactions. This was also observed for ALP simply physisorbed on paper. The retention aid polymers instigated a rapid initial deactivation which significantly decreased the longevity of the enzymatic papers. This suggests some enzyme-polymer interaction probably affecting the enzyme tertiary structure. A deactivation mathematical model predicting the enzymatic paper half-life was developed.

  11. Effect of fatty acids and oils on photodegradation of azadirachtin-A.

    Johnson, S; Patra, D; Dureja, P


    Azadirachtin-A on exposure to UV-light (254 nm) as a thin film on glass surface gave a isomerised (Z)-2-methylbut-2-enoate product. Half-life of azadirachtin-A as thin film under UV light was found to be 48 min. Azadirachtin-A was irradiated along with saturated and unsaturated fatty acids, and fatty oils under ultra-violet light as thin film. Saturated fatty acid increased the rate of photodegradation of azadirachtin-A, whereas unsaturated fatty acids such as oleic, linoleic and elaidic acid reduced the rate of degradation. Castor, linseed and olive oil accelerated the rate of degradation, whereas neem oil showed no or little change in the rate of degradation of azadirachtin-A. None of these fatty acids and fatty oils were effective in controlling the rate of degradation of azadirachtin-A under UV-light as thin film.

  12. Effects of 5-FU.

    Wigmore, Peter M; Mustafa, Sarah; El-Beltagy, Maha; Lyons, Laura; Umka, Jariya; Bennett, Geoff


    5-fluorouracil (5-FU) is a chemotherapeutical agent used to treat cancers including breast and colorectal. Working as an antimetabolite to prevent cell proliferation, it primarily inhibits the enzyme thymidylate synthase blocking the thymidine formation required for DNA synthesis. Although having a relatively short half-life (fog" These accounts have come primarily from patients undergoing treatment for breast cancer who report symptoms including confusion and memory impairment, which can last for months to years. Psychometric studies of patients have suffered from confounding variables, which has led to the use of rodent models to assess the cognitive effects of this drug. Researchers have used behavioral and physiological tests including the Morris water maze, novel object location/recognition tests, shock motivated T-maze, sensory gating and conditioning, to investigate the effect of this drug on cognition. The variety of cognitive tests and the difference in dosing and administration of 5-FU has led to varied results, possibly due to the different brain regions associated with each test and the subtlety of the drug's effect, but overall these studies indicates that 5-FU has a negative effect on memory, executive function and sensory gating. 5-FU has also been demonstrated to have biochemical and structural changes on specific regions of the brain. Evidence shows it can induce apoptosis and depress cell proliferation in the neurogenic regions of the adult brain including the sub granular zone (SGZ) within the hippocampus and in oligodendrocyte precursor populations within white matter tracts. Furthermore, investigations indicate levels ofdoublecortin, a marker for newly formed neurons and brain derived neurotrophic factor, a cell survival modulator, are also reduced by 5-FU in the SGZ. Thus, 5-FU appears to have a lasting negative impact on cognition and to affect cellular and biochemical markers in various brain regions. Further work is needed to understand the

  13. In vivo animal demonstration of the effect of vasoactive drugs using /sup 195m/Au and gamma camera techniques

    Bourgeois, P.; Bourgeois, F.; Lupo, P.; Vooren, J.P. van; Clercx, C.


    /sup 195m/Au, an ultrashort lived (physical half life = 30.5 s), generator produced, radionuclide, has been used in an animal model to study, by gamma camera techniques, the peripheral effects of the vasoactive drugs norepinephrine and sodium nitroprusside systemically administered or epinephrine intraarterially injected, at various concentrations. According to the results obtained by the analysis of time on the proximal and distal parts of the limbs, the well known hemodynamic changes induced by these drugs, vascoconstriction (resulting in a decrease of the distal acitvity recorded), or vasodilatation (shortening the time of radioactivity appearance), could be observed. It is concluded that gamma camera techniques using the ultrashort lived radionuclide /sup 195m/Au allow the in vivo study of the effects of vasoactive drugs in an animal model and potentially in clinical situations.

  14. In vivo Pharm acodynam ic Effect of Thiam phenicol in Serum of Carassius auratus on Aerom onas hydrophila

    Yang; Hongbo; Wang; Di; LU; Tongyan


    This study was to investigate the in vitro pharmacodynamic effect of thiamphenicol( TAP) in serum of Carassius auratus on Aeromonas hydrophila. By combining the in vivo pharmacokinetics and in vitro pharmacodynamics,the pharmacodynamic effect of TAP on Aeromonas hydrophila was studied,and the data were processed and analyzed by software Excel 2007,Kinetica3P97 and Kinetica4. 4. The results showed that oral administration of singly 30 mg /kg TAP assumed a rapid assimilation-quickly peaking-slowly dispelling trend in Carassius auratus. The related parameters were measured as follows: time of peaked plasma concentration of TAP( Tpeak) of 1.5 h,peak concentration( Cmax) of 37.172 μg/mL and absorption rate( ka) of 1.523 h,half-life period T1/2( ka) of 0.455 h,lag time( TL)of 0. 02 h,elimination half life T1/2( ke) of 16.712 h. The half maximal effective concentration( EC50) was 14.28 h. The PK-PD parameters were 32.41 h in AUC0- 24/ MICserumand 23. 23 in Cmax/MICserum. Employing an inhibitory Sigmoid Emax model,the administration dosage of TAP for preventing Aeromonas hydrophila-caused bacterial septicemia was 8. 61- 46. 20 mg /kg in clinical application. Based on these,we proposed the optimal administration route for preventing and controlling the Aeromonas hydrophila-caused bacterial septicemia: delivering TAP at the ratio of 46. 20 mg /kg on diseased Carassius auratus by mixing with baits or oral administration,followed by delivering with baits at ratio of 8. 61 mg /kg for preventing the Aeromonas hydrophila-caused bacterial septicemia. The results provided references for applying thiamphenicol for preventing and controlling the bacterial septicemia in aquatic livestock.

  15. Effect of solar radiation on the optical properties and molecular composition of laboratory proxies of atmospheric brown carbon.

    Lee, Hyun Ji Julie; Aiona, Paige Kuuipo; Laskin, Alexander; Laskin, Julia; Nizkorodov, Sergey A


    Sources, optical properties, and chemical composition of atmospheric brown carbon (BrC) aerosol are uncertain, making it challenging to estimate its contribution to radiative forcing. Furthermore, optical properties of BrC may change significantly during its atmospheric aging. We examined the effect of photolysis on the molecular composition, mass absorption coefficient, and fluorescence of secondary organic aerosol (SOA) prepared by high-NOx photooxidation of naphthalene (NAP SOA). Our experiments were designed to model photolysis processes of NAP SOA compounds dissolved in cloud or fog droplets. Aqueous solutions of NAP SOA were observed to photobleach (i.e., lose their ability to absorb visible radiation) with an effective half-life of ∼15 h (with sun in its zenith) for the loss of near-UV (300-400 nm) absorbance. The molecular composition of NAP SOA was significantly modified by photolysis, with the average SOA formula changing from C14.1H14.5O5.1N0.085 to C11.8H14.9O4.5N0.023 after 4 h of irradiation. However, the average O/C ratio did not change significantly, suggesting that it is not a good metric for assessing the extent of photolysis-driven aging in NAP SOA (and in BrC in general). In contrast to NAP SOA, the photobleaching of BrC material produced by the reaction of limonene + ozone SOA with ammonia vapor (aged LIM/O3 SOA) was much faster, but it did not result in a significant change in average molecular composition. The characteristic absorbance of the aged LIM/O3 SOA in the 450-600 nm range decayed with an effective half-life of <0.5 h. These results emphasize the highly variable and dynamic nature of different types of atmospheric BrC.

  16. A comprehensive evaluation of health effects in Europe-two decades after Chernobyl

    Seidel, C.; Maringer, F.J. [University of Natural Resources and Applied Life Science Vienna, Low-Level Counting Lab. Arsenal, Wien (Austria); Maringer, F.J. [BEV-Federal Office of Metrology and Surveying (BEV), Wien (Austria); Bossew, P. [BEV-Federal Office of Metrology and Surveying (BEV), Mathematics and analytics, Vienna (Austria)


    This report sums up radioactive environmental contamination due to the Chernobyl accident in 1986 in various regions all over Europe (Ukraine, Belarus, Russia, Sweden, Austria and Greece). Most of the radionuclides released with the reactor accident possess short-lives (e.g. 131 I) of a few hours or several days and weeks or were deposed in low quantities (e.g. 90 Sr). So the main focus was put on 137 Cs, because this radionuclide has a long half-life (30 years), is measurable till this day and gives a presentable view of radiation exposure in contaminated regions. The decrease of 137 Cs activity concentrations in soil, surface water, foodstuffs and air was shown in the course of time. The comparison of radioactive environmental contamination shows, that the 137 Cs-activity concentration in nearly all media has decreased faster than the physical half-life. Part of this elaboration was also to describe the contribution of the reactor accident to the radiation exposure of selected population groups in the last 20 years. The second part of the report follows a valuation of European studies, which are linked to late health effects of the Chernobyl accident specially thyroid cancer, leukaemia and other solid tumours. These studies has been discussed and evaluated. Only in countries with the highest impact like Ukraine, Belarus and Russia, an increased number of infant thyroid cancer has been observed but up to now no increases in leukaemia or malignant deceases in this or other European countries can be detected. (authors)

  17. Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans.

    Dolder, Patrick C; Schmid, Yasmin; Haschke, Manuel; Rentsch, Katharina M; Liechti, Matthias E


    The pharmacokinetics of oral lysergic acid diethylamide are unknown despite its common recreational use and renewed interest in its use in psychiatric research and practice. We characterized the pharmacokinetic profile, pharmacokinetic-pharmacodynamic relationship, and urine recovery of lysergic acid diethylamide and its main metabolite after administration of a single oral dose of lysergic acid diethylamide (200 μg) in 8 male and 8 female healthy subjects. Plasma lysergic acid diethylamide concentrations were quantifiable (>0.1 ng/mL) in all the subjects up to 12 hours after administration. Maximal concentrations of lysergic acid diethylamide (mean±SD: 4.5±1.4 ng/mL) were reached (median, range) 1.5 (0.5-4) hours after administration. Concentrations then decreased following first-order kinetics with a half-life of 3.6±0.9 hours up to 12 hours and slower elimination thereafter with a terminal half-life of 8.9±5.9 hours. One percent of the orally administered lysergic acid diethylamide was eliminated in urine as lysergic acid diethylamide, and 13% was eliminated as 2-oxo-3-hydroxy-lysergic acid diethylamide within 24 hours. No sex differences were observed in the pharmacokinetic profiles of lysergic acid diethylamide. The acute subjective and sympathomimetic responses to lysergic acid diethylamide lasted up to 12 hours and were closely associated with the concentrations in plasma over time and exhibited no acute tolerance. These first data on the pharmacokinetics and concentration-effect relationship of oral lysergic acid diethylamide are relevant for further clinical studies and serve as a reference for the assessment of intoxication with lysergic acid diethylamide. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  18. The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

    Tanaka, E; Nakamura, K


    The effect of pretreatment for 7 days with either roxatidine acetate 75 mg twice daily or cimetidine 200 mg four times daily on the kinetics of antipyrine (AP), trimethadione (TMO) and indocyanine green (ICG) was studied in seven healthy, male, nonsmoking subjects. After pretreatment with cimetidine, the plasma clearances (CL) of AP and TMO were significantly lower and the elimination half-life (t1/2) of AP was significantly increased. The volumes of distribution (V) of AP and TMO were not affected. After roxatidine acetate, the pharmacokinetics of AP and TMO were unchanged. The cumulative renal excretion (% dose) and formation clearance of 3-hydroxymethyl-3-nor-antipyrine (NORA) were lowered by cimetidine treatment, but not following the administration of roxatidine acetate. ICG clearance was not changed significantly by either pretreatment. The results of this study show that roxatidine acetate does not impair the metabolism of three model substrates used to assess hepatic drug clearance.

  19. Tolerability, pharmacokinetics, and neuroendocrine effects of PRX-00023, a novel 5-HT1A agonist, in healthy subjects.

    Iyer, Ganesh R; Reinhard, John F; Oshana, Scott; Kauffman, Michael; Donahue, Stephen


    PRX-00023 is a novel, nonazapirone 5-HT1A agonist in clinical development for treatment of affective disorders. The objectives of the initial clinical phase I studies (a single ascending dose study and multiple dose-ascending and high-dose titration studies) were to measure the pharmacokinetics, pharmacodynamic (neuroendocrine) effects, and tolerability of PRX-00023 in healthy subjects. The studies evaluated 10-mg to 150-mg doses of PRX-00023 in up to 112 healthy male and female subjects aged 18 to 54 years. Single and multiple oral doses of PRX-00023 were found to be safe and well tolerated in healthy subjects. PRX-00023 was absorbed relatively rapidly, with a tmax of 0.5 to 2 hours, and eliminated with a half-life of approximately 12 hours. PRX-00023 treatment transiently increased blood prolactin levels 2 to 3 hours after administration, consistent with its mechanism as a 5-HT1A agonist.

  20. Effect of olive-mill waste addition to agricultural soil on the enantioselective behavior of the chiral fungicide metalaxyl.

    Gámiz, Beatriz; Celis, Rafael; Hermosín, M Carmen; Cornejo, Juan


    Certain soil management practices can affect the enantioselective behavior of chiral pesticide enantiomers in agricultural soils. In this work, laboratory experiments were conducted to study the effects of olive-mill waste (OMW) addition to a Mediterranean agricultural soil on the enantioselectivity of sorption, degradation, and leaching processes of the chiral fungicide metalaxyl. Sorption-desorption isotherms indicated that the sorption of metalaxyl enantiomers by unamended and OMW-amended soil (2% w/w) was non-enantioselective and that OMW addition had little effect on the extent of sorption of metalaxyl enantiomers by the soil. Soil incubation experiments revealed that the degradation of metalaxyl in unamended soil was highly enantioselective, with R-metalaxyl being degraded faster (t1/2 = 12 days) than S-metalaxyl (t1/2 = 39 days). OMW addition to the soil increased the half-life of the biologically-active R-metalaxyl enantiomer from 12 to 28 days, and decreased the half-life of the non-active S-metalaxyl enantiomer from 39 to 33 days. Consequently, the enantioselectivity of metalaxyl degradation in the soil was greatly reduced upon OMW addition. Column leaching data were consistent with batch sorption and incubation results, showing similar retardation of S- and R-metalaxyl in unamended and OMW-amended soil and enantioselective leaching of the fungicide only in unamended soil. The results have important implications regarding the biological efficacy and environmental impact of the fungicide when applied as a mixture of enantiomers or racemate to OMW-treated soils. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Aspects of biochemical effects by hyperthermia

    Streffer, C.


    Hyperthermia caused an immediate decrease of DNA, RNA, and protein synthesis. The latter process was most sensitive. Initiation of DNA synthesis at the transition from G1-to S-phase and at the start of new replication units were inhibited. These effects were responsible for the growth delay of cells and were potentiated with irradiation. The immediate inhibition of protein synthesis was due mainly to a disaggregation of the synthesizing mechanisms. It led to a decrease of enzyme activities with a short biological half-life, e.g., ornithine decarboxylase. Lysosomal hydrolytic activities might be enhanced after hyperthermia and contribute to tissue damage. During hyperthermia, glycogen breakdown and glucose turnover through glycolysis and the citrate cycle were apparently increased, but after hyperthermia, respiration and glycolysis were reduced. No lactate accumulation occurred, but other acidic metabolites were enhanced and could induce a metabolic acidosis hours later. A glucose load potentiated the effects on respiration and glycolysis. Immediately after hyperthermia, a lactate accumulation was observed under these conditions. A formula is given by which the ratios of reduced to oxidized substrates might indicate the redox state in different cellular compartments, with oxygen pressure, and during other metabolic conditions. Such changes of the intracellular milieu are important for the thermosensitivity of cells.

  2. Effects of tenoxicam on renal function and the disposition of inulin and p-aminohippurate in healthy volunteers and patients with chronic renal failure.

    Freestone, S; McAuslane, J A; Prescott, L F


    1. The effects of tenoxicam on renal function were studied in 10 patients with chronic renal failure (creatinine clearance 46.7 +/- 11.9 ml min-1 1.73 m-2) and eight healthy volunteers. A parallel treatment control group of eight healthy volunteers received placebo. Tenoxicam was given orally in a dose of 40 mg daily for 2 days followed by 20 mg daily for a further 8 days. Renal function was assessed by measurement of the renal clearances of inulin and p-aminohippurate (PAH) using the single injection technique before and during administration of tenoxicam. 2. In the healthy volunteers there were no changes in glomerular filtration rate, effective renal plasma flow, or the urinary excretion of N-acetylglucosaminidase and beta 2-microglobulin on the 3rd and 10th days of treatment with tenoxicam. The mean urinary excretion of prostaglandins E2 and 6-keto F1 alpha decreased during treatment but there was great individual variation and the differences were not statistically significant. Tenoxicam had no effect on the half-life, clearance, volume of distribution or urinary recovery of inulin and PAH. 3. There was no significant change in the clearance of inulin and creatinine after treatment with tenoxicam for 10 days in the patients with chronic renal failure. However, in this group there was a significant increase in plasma creatinine on the 3rd and 6th days with a return to pretreatment levels by the 10th day. The administration of tenoxicam for 10 days was associated with a small but significant increase in the plasma half-life and volume of distribution of inulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1958445

  3. Pharmacokinetics of digoxin cross-reacting substances in patients with acute yellow Oleander (Thevetia peruviana) poisoning, including the effect of activated charcoal.

    Roberts, Darren M; Southcott, Emma; Potter, Julia M; Roberts, Michael S; Eddleston, Michael; Buckley, Nick A


    Intentional self-poisonings with seeds from the yellow oleander tree (Thevetia peruviana) are widely reported. Activated charcoal has been suggested to benefit patients with yellow oleander poisoning by reducing absorption and/or facilitating elimination. Two recent randomized controlled trials (RCTs) assessing the efficacy of activated charcoal yielded conflicting outcomes in terms of mortality. The effect of activated charcoal on the pharmacokinetics of Thevetia cardenolides has not been assessed. This information may be useful for determining whether further studies are necessary. Serial blood samples were obtained from patients enrolled in an RCT assessing the relative efficacy of single-dose and multiple-dose activated charcoal (SDAC and MDAC, respectively) compared with no activated charcoal (NoAC). The concentration of Thevetia cardenolides was estimated with a digoxin immunoassay. The effect of activated charcoal on cardenolide pharmacokinetics was compared between treatment groups by determining the area under the curve for each patient in the 24 hours following admission, the 24-hour mean residence time, and regression lines obtained from serial concentration points, adjusted for exposure. Erratic and prolonged absorption patterns were noted in each patient group. The apparent terminal half-life was highly variable, with a median time of 42.9 hours. There was a reduction in 24-hour mean residence time and in the apparent terminal half-life estimated from linear regression in patients administered activated charcoal, versus the control group (NoAC). This effect was approximately equal in patients administered MDAC or SDAC. Activated charcoal appears to favorably influence the pharmacokinetic profile of Thevetia cardenolides in patients with acute self-poisoning and may have clinical benefits. Given the conflicting clinical outcomes noted in previous RCTs, these mechanistic data support the need for further studies to determine whether a particular subgroup

  4. Fast and cost-effective cyclotron production of (61)Cu using a (nat)Zn liquid target: an opportunity for radiopharmaceutical production and R&D.

    do Carmo, S J C; Alves, V H P; Alves, F; Abrunhosa, A J


    Following our previous work on the production of radiometals, such as (64)Cu and (68)Ga, through the irradiation of liquid targets using a medical cyclotron, we describe in this paper a technique to produce (61)Cu through the irradiation of natural zinc using a liquid target. The proposed method is very cost-effective, as it avoids the use of expensive enriched material, and is fast, as a purified solution of (61)CuCl2 is obtained in less than 30 min after the end of beam. Considering its moderate half-life of 3.33 h and favourable decay properties as a positron emitter, (61)Cu is a very attractive nuclide for the labelling of PET tracers for pre-clinical and clinical use with PET as well as to support the intense R&D programmes being carried out worldwide by taking advantage of the rich and versatile chemistry of copper.

  5. A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: Effects of tumor burden and antigen expression

    Scheinberg, D.A.; Straus, D.J.; Yeh, S.D.; Divgi, C.; Garin-Chesa, P.; Graham, M.; Pentlow, K.; Coit, D.; Oettgen, H.F.; Old, L.J. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA))


    Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I.

  6. The effect of mirabegron, a potent and selective β3-adrenoceptor agonist, on the pharmacokinetics of CYP2D6 substrates desipramine and metoprolol.

    Krauwinkel, Walter; Dickinson, James; Schaddelee, Marloes; Meijer, John; Tretter, Reiner; van de Wetering, Jeroen; Strabach, Gregory; van Gelderen, Marcel


    Mirabegron is a potent and selective β3-adrenoceptor agonist developed for the treatment of overactive bladder. In vitro studies demonstrated that mirabegron partly acts as a (quasi-) irreversible, metabolism-dependent inhibitor of CYP2D6. The effect of steady-state mirabegron on single doses of the sensitive CYP2D6 substrates metoprolol (100 mg) and desipramine (50 mg) was assessed in two open-label, one-sequence crossover studies in healthy subjects (CYP2D6 extensive metabolizers). Mirabegron 160 mg/day increased metoprolol maximum plasma concentration (C max) 1.90-fold (90 % confidence interval [CI] 1.54; 2.33) and total exposure (AUC0-∞) 3.29-fold (90 % CI 2.70; 4.00) in 12 males (study 1). Mean metoprolol half-life increased from 2.96 to 4.11 h. α-Hydroxymetoprolol C max and AUC to last measurable concentration decreased 2.6-fold and 2.2-fold, respectively. In study 2, mirabegron 100 mg/day increased desipramine C max 1.79-fold (90 % CI 1.69; 1.90) and AUC0-∞ 3.41-fold (90 % CI 3.07; 3.80) in 14 males and 14 females. Mean desipramine half-life increased from 19.5 to 35.8 h. C max of 2-hydroxydesipramine decreased ~twofold, while AUC increased ~1.3-fold. Desipramine was administered again 2 weeks after the last mirabegron dose. Desipramine C max and AUC0-∞ were still ~1.13-fold increased; the 90 % CIs fell within the 0.80-1.25 interval. All treatments were well tolerated. In conclusion, mirabegron is a moderate CYP2D6 inhibitor (ratio and 90 % CI <5.0).

  7. Propylthiouracil, independent of its antithyroid effect, decreases VSMC collagen expression.

    Chen, Wei-Jan; Pang, Jong-Hwei S; Lin, Kwang-Huei; Yang, Su-Hui


    Propylthiouracil (PTU), in addition to its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. Because collagen accumulation is the major contributor to the growth of atherosclerotic lesions and the neointimal formation after arterial injury, the aim of this study is to investigate the impact of PTU on collagen regulation. In the rat carotid injury model, PTU administration reversed the up-regulation of collagen in the neointima induced by balloon injury. In vitro, vascular smooth muscle cells (VSMCs), the main origin of arterial collagen, were treated with PTU. Propylthiouracil caused a concentration-dependent decrease in collagen I and III steady-state protein and mRNA levels, as determined by immuno-cytochemistry, Western, and/or Northern blot analyses. Transient transfection experiments using rat type I collagen promoter construct showed that PTU failed to affect collagen gene transcription in VSMCs. Actinomycin D studies demonstrated that the half-life of collagens mRNA decreased with PTU treatment, suggesting that PTU down-regulates collagen expression predominantly at the post-transcriptional level. Taken together, these data suggest that PTU inhibits VSMC collagen production via destabilization of collagen mRNA that contributes to its beneficial effect on atherogenesis and neointimal formation after arterial injury. However, whether the destabilization of collagen may induce plaque rupture in PTU-treated arteries merits further investigation.

  8. Effect of household processing on fenazaquin residues in okra fruits.

    Duhan, Anil; Kumari, Beena; Gulati, Rachna


    Fenazaquin (4-[[4 (1,1-dimethylethyl) phenyl] ethoxy]quinazoline) is a new acaricide of the quinazoline class. Residue levels of fenazaquin were determined in unprocessed and processed okra fruits to evaluate the effect of different processes (washing, boiling and washing followed by boiling) in reduction of residues of this pesticide in okra. The study was carried out on okra crop (Variety, Varsha Uphar) in research farm of Chaudhary Charan Singh Haryana Agricultural University, Hisar with application of fenazaquin (Magister 10 EC) @ 125 ga.i./ha (Single Dose, T(1)) and 250 g a.i./ha (Double Dose, T(2)). Samples of okra fruits were collected on 0, 3, 7, 15 days after treatment and at harvest (30 days). Residues were estimated by gas chromatograph equipped with capillary column and nitrogen phosphorus detector. Residues reached below maximum residue limit of 0.01 mg/kg at harvest. The residues dissipated with half-life period of 3.13 days at lower dose and 4.43 days at higher dose. Processing is shown to be very effective in reducing the levels of fenazaquin residues in okra fruits. Maximum reduction (60-61%) was observed by washing + boiling followed by boiling/cooking (38-40%) and then by washing (31-32%).

  9. Ultra low fluence rate photodynamic therapy: simulation of light emitted by the Cerenkov effect

    Gonzales, Jonathan; Wang, Fred; Zamora, Genesis; Trinidad, Anthony; Marcu, Laura; Cherry, Simon; Hirschberg, Henry


    PDT has been shown to be most effective at low fluence rates. Many radionuclides used for both diagnostic and therapeutic purposes produce measurable amounts of visible radiation when they decay via the Cerenkov effect which occurs when a charged particle travels faster in a dielectric medium than the speed of light in that medium. Cerenkov radiation from radiopharmaceuticals could serve as a source of extended duration, low level "internal" light, to mediate PDT, with the ultimate goals of overcoming some its current limitations. Using laser light, we are exploring the effects of fluence rates that could be generated by Cerenkov radiation on PDT efficacy. ALA or TPPS2a mediated PDT of rat gliomas monolayers or multicell spheroids ( F98, C6) was performed with 410 nm laser light exposure over an extended period of 24-96hrs. Photosensitizers were delivered either as a bolus or continuously with light exposure. At fluence rate of 20μW/cm2 effective PDT was obtained as measured by decrease in cell viability or inhibition of spheroid growth. PDT is effective at ultra low fluence rates if given over long time periods. No lower threshold has been ascertained. Since the half-life of 90Y, a radionuclide with a high Cherenkov yield is 64 hrs it is a good candidate to supply sufficient light activation for PDT. The combination of radionuclide and photodynamic therapies could improve the effectiveness of cancer treatment by exploiting synergies between these two modalities.

  10. In vivo and in vitro percutaneous absorption of [{sup 14}C]pyrene in sprague dawley male rats: skin reservoir effect and consequence on urinary 1-OH pyrene excretion

    Payan, Jean-Paul; Lafontaine, Michel; Simon, Patrice; Marquet, Fabrice; Champmartin-Gendre, Catherine; Beydon, Dominique; Ferrari, Elisabeth [Institut National de Recherche et de Securite, Vandoeuvre (France)


    The skin reservoir effect of [{sup 14}C]pyrene (in vivo and in vitro) on percutaneous absorption was determined in male Sprague Dawley rats. The urinary 1-OHpyrene (1-OHPy) excretion was compared between dermal exposure and intravenous administration. In vivo, the percutaneous absorption flux of [{sup 14}C]pyrene (200 {mu}g/cm{sup 2}; 50 {mu}L/cm{sup 2} of ethanol) determined by sacrificing batches of rats after different exposure times over 4.5 h was 1.0{+-}0.1 {mu}g/cm{sup 2} h{sup -1}. During exposure, penetration flux was twofold higher than absorption flux, indicating a gradual accumulation of pyrene in the skin. [{sup 14}C] skin content at the end of exposure was 16{mu}g/cm{sup 2}, which decreased gradually over time to 2 {mu}g/cm{sup 2} 68 h after the end of exposure. The total absorbed dose during exposure was threefold lower than that after exposure, indicating a high contribution of pyrene skin content to the systemic availability of the compound. Similar results were obtained in vitro. The apparent elimination rate of [{sup 14}C]pyrene (23 h) contained in the skin after an exposure of 4.5 h was similar to the apparent urinary excretion half life of 1-OHPy (21 h). These values are threefold higher than the urinary excretion half life of 1-OHPy after an intravenous administration of pyrene (0.5 mg/kg). In conclusion, absorbed dose and percutaneous absorption flux were well estimated from the 1-OHPy urinary excretion rate. For risk assessment purposes, the penetration flux rather than the absorption flux should be taken into account for topical pyrene exposure. (orig.)

  11. Effect of heavy metals on, and handling by, the kidney.

    Barbier, Olivier; Jacquillet, Grégory; Tauc, Michel; Cougnon, Marc; Poujeol, Philippe


    Heavy metals such as cadmium (Cd), mercury (Hg), lead (Pb), chromium (Cr) and platinum (Pt) are a major environmental and occupational hazard. Unfortunately, these non-essential elements are toxic at very low doses and non-biodegradable with a very long biological half-life. Thus, exposure to heavy metals is potentially harmful. Because of its ability to reabsorb and accumulate divalent metals, the kidney is the first target organ of heavy metal toxicity. The extent of renal damage by heavy metals depends on the nature, the dose, route and duration of exposure. Both acute and chronic intoxication have been demonstrated to cause nephropathies, with various levels of severity ranging from tubular dysfunctions like acquired Fanconi syndrome to severe renal failure leading occasionally to death. Very varied pathways are involved in uptake of heavy metals by the epithelium, depending on the form (free or bound) of the metal and the segment of the nephron where reabsorption occurs (proximal tubule, loop of Henle, distal tubule and terminal segments). In this review, we address the putative uptake pathways involved along the nephron, the mechanisms of intracellular sequestration and detoxification and the nephropathies caused by heavy metals. We also tackle the question of the possible therapeutic means of decreasing the toxic effect of heavy metals by increasing their urinary excretion without affecting the renal uptake of essential trace elements. We have chosen to focus mainly on Cd, Hg and Pb and on in vivo studies.

  12. Effect of pregnancy on topiramate pharmacokinetics in rabbits.

    Matar, Kamal M; Marafie, Najlaa A


    Pregnancy is associated with various physiological changes that may lead to significant alterations in the pharmacokinetic profiles of many drugs. The present study was designed to investigate the potential effects of pregnancy on the pharmacokinetics of topiramate (TPM) in the rabbit model. Nineteen female New Zealand white rabbits (nine pregnant and 10 non-pregnant) were used in this study. Blood samples were collected from the animals just before receiving TPM orally at a dose of 20 mg/kg and then serially for up to 24 h. TPM plasma samples were analysed using a validated tandem mass spectrometric (LC-MS/MS) method. The mean values of TPM pharmacokinetic parameters (t(1/2), T(max), AUC(0-∞), and CL/F) were significantly modified in pregnant rabbits as compared with non-pregnant group. Pregnancy significantly (P < 0.05) increased TPM half-life (t(1/2)), time to attain the maximum plasma concentration (T(max)), and the area under TPM plasma concentration-time curve (AUC(0-∞)) and decreased the drug's oral clearance (CL/F) compared with non-pregnancy state in rabbits. The present study demonstrates that pregnancy alters the pharmacokinetics of TPM in rabbits in late gestational period and considerable inter-animal variability was observed. The findings of the present study indicate that TPM CL/F is decreased during late pregnancy in the rabbit model.

  13. Effects of DNA replication on mRNA noise.

    Peterson, Joseph R; Cole, John A; Fei, Jingyi; Ha, Taekjip; Luthey-Schulten, Zaida A


    There are several sources of fluctuations in gene expression. Here we study the effects of time-dependent DNA replication, itself a tightly controlled process, on noise in mRNA levels. Stochastic simulations of constitutive and regulated gene expression are used to analyze the time-averaged mean and variation in each case. The simulations demonstrate that to capture mRNA distributions correctly, chromosome replication must be realistically modeled. Slow relaxation of mRNA from the low copy number steady state before gene replication to the high steady state after replication is set by the transcript's half-life and contributes significantly to the shape of the mRNA distribution. Consequently both the intrinsic kinetics and the gene location play an important role in accounting for the mRNA average and variance. Exact analytic expressions for moments of the mRNA distributions that depend on the DNA copy number, gene location, cell doubling time, and the rates of transcription and degradation are derived for the case of constitutive expression and subsequently extended to provide approximate corrections for regulated expression and RNA polymerase variability. Comparisons of the simulated models and analytical expressions to experimentally measured mRNA distributions show that they better capture the physics of the system than previous theories.

  14. Pharmacokinetics of amikacin during hemodialysis and peritoneal dialysis

    Regeur, L; Colding, H; Jensen, H


    renal function. During hemodialysis the half-life decreased to less than 10% (5.6 h) of the pretreatment value. The effectiveness of peritoneal dialysis was less as the half-life decreased to only about 30% (17.9 h) of the pretreatment value. During the dialyses a significant correlation between...

  15. Concentrations of MDPV in rat striatum correlate with the psychostimulant effect.

    Novellas, Judith; López-Arnau, Raúl; Carbó, Marcel Li; Pubill, David; Camarasa, Jorge; Escubedo, Elena


    3,4-methylenedioxypyrovalerone or MDPV is a synthetic cathinone with psychostimulant properties more potent than cocaine. We quantified this drug in the striatum after subcutaneous administration to rats. MDPV reached the brain around 5 min after its administration and peaked at 20-25 min later. The elimination half-life in the striatum (61 min) correlates with the decrease in the psychostimulant effect after 60 min. Around 11% of the administered dose reached the striatum and, considering a homogeneous brain distribution, we determined that around 86% of the plasma MDPV is distributed to the brain. MDPV induced a dose-dependent increase in locomotor activity, rearing behaviour and stereotypies, all prevented by haloperidol. A plot of locomotor activity or stereotypies versus MDPV striatal concentrations over time showed a direct relationship between factors. No free MDPV metabolites were detected in plasma, at any time, but hydrolysis with glucuronidase allowed us to identify mainly three metabolites, one of them for the first time in rat plasma. The present results contribute to evidence that MDPV induces hyperlocomotion mainly through a dopamine-dependent mechanism. Good correlation between behavioural effects and striatal levels of MDPV leads us to conclude that its psychostimulant effect is mainly due to a striatal distribution of the substance. The present research provides useful information on the pharmacokinetics of MDPV, and can help design new experiments with kinetics data as well as provide a better understanding of the effects of MDPV in humans and its potential interactions. © The Author(s) 2015.

  16. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury

    Hong-fei Li


    Full Text Available Nerve growth factor (NGF plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.

  17. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury.

    Li, Hong-Fei; Wang, Yi-Ru; Huo, Hui-Ping; Wang, Yue-Xiang; Tang, Jie


    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.

  18. Effective Dose of Radon 222 Bottled Water in Different Age Groups Humans: Bandar Abbas City, Iran.

    Fakhri, Yadolah; Mahvi, Amir Hossein; Langarizadeh, Ghazaleh; Zandsalimi, Yahya; Amirhajeloo, Leila Rasouli; Kargosha, Morteza; Moradi, Mahboobeh; Moradi, Bigard; Mirzaei, Maryam


    Radon 222 is a natural radioactive element with a half-life of 3.8 days. It is odorless and colorless as well as water-soluble. Consuming waters which contain high concentration of 222Rn would increase the effective dose received by different age groups. It would also be followed by an increased prevalence of cancer. In this research, 72 samples of the most commonly used bottled water in Bandar Abbas were collected in 3 consecutive months, May, June and July of 2013. Concentration 222Rn of was measured by radon-meter model RTM166-2. The effective dose received by the 4 age groups, male and female adults as well as children and infants was estimated using the equation proposed by UNSCEAR. The results revealed that the mean and range concentration of 222Rn in bottled waters were 641±9 Bq/m3 and 0-901 Bq/m3, respectively. The mean concentration of 222Rn in the well-known Marks followed this Zam Zam>Bishe>Koohrng>Dassani>Christal>Polour>Damavand>Sivan. Infants were observed to receive a higher effective dose than children. The highest and lowest effective dose received was found to belong to male adults and children, respectively.

  19. Effective Dose Radon 222 of the Tap Water in Children and Adults People; Minab City, Iran.

    Fakhri, Yadolah; Kargosha, Morteza; Langarizadeh, Ghazaleh; Zandsalimi, Yahya; Rasouli Amirhajeloo, Leila; Moradi, Mahboobeh; Moradi, Bigard; Mirzaei, Maryam


    (222)Rn is a radioactive, odorless, and colorless element which has a half-life of 3.83 days. One of (222)Rn main resources are Groundwater (wells, springs, etc.). Hence, the use of groundwater with high concentration of (222)Rn can increase the risk of lung and stomach cancers. Concentration of (222)Rn in tap water of Minab city in two temperatures 5 and 15 ºC was measured by radon meter model RTM1668-2. The effective dose was calculated by equations proposed by UNSCEAR. Geometric mean concentration of (222)Rn in drinking water was found to be 0.78±0.06 and 0.46±0.04 Bq/l at 5 and 15 ̊C (p value222)Rn at 5 and 15 ̊C were estimated 0.0021 and 0.0012mSv/y, respectively. Geometric mean concentration in (222)Rn drinking water and effective dose received from drinking water and inhalation of (222)Rn is lower than WHO and EPA standard limits. Increasing temperature of drinking water will decrease the effective dose received. Annual Effective dose received from inhalation and consumption of (222)Rn in drinking water in children is more than adults.

  20. Effect of Recombinant Human Lecithin Cholesterol Acyltransferase Infusion on Lipoprotein Metabolism in Mice

    Vaisman, Boris; Auerbach, Bruce; Krause, Brian R.; Homan, Reyn; Stonik, John; Csako, Gyorgy; Shamburek, Robert; Remaley, Alan T.


    Lecithin cholesterol acyl transferase (LCAT) deficiency is associated with low high-density lipoprotein (HDL) and the presence of an abnormal lipoprotein called lipoprotein X (Lp-X) that contributes to end-stage renal disease. We examined the possibility of using LCAT an as enzyme replacement therapy agent by testing the infusion of human recombinant (r)LCAT into several mouse models of LCAT deficiency. Infusion of plasma from human LCAT transgenic mice into LCAT-knockout (KO) mice rapidly increased HDL-cholesterol (C) and lowered cholesterol in fractions containing very-low-density lipoprotein (VLDL) and Lp-X. rLCAT was produced in a stably transfected human embryonic kidney 293f cell line and purified to homogeneity, with a specific activity of 1850 nmol/mg/h. Infusion of rLCAT intravenously, subcutaneously, or intramuscularly into human apoA-I transgenic mice showed a nearly identical effect in increasing HDL-C approximately 2-fold. When rLCAT was intravenously injected into LCAT-KO mice, it showed a similar effect as plasma from human LCAT transgenic mice in correcting the abnormal lipoprotein profile, but it had a considerably shorter half-life of approximately 1.23 ± 0.63 versus 8.29 ± 1.82 h for the plasma infusion. rLCAT intravenously injected in LCAT-KO mice crossed with human apolipoprotein (apo)A-I transgenic mice had a half-life of 7.39 ± 2.1 h and increased HDL-C more than 8-fold. rLCAT treatment of LCAT-KO mice was found to increase cholesterol efflux to HDL isolated from mice when added to cells transfected with either ATP-binding cassette (ABC) transporter A1 or ABCG1. In summary, rLCAT treatment rapidly restored the normal lipoprotein phenotype in LCAT-KO mice and increased cholesterol efflux, suggesting the possibility of using rLCAT as an enzyme replacement therapy agent for LCAT deficiency. PMID:20605907

  1. Effect of Misoprostol on the Pharmacokinetics of Sustained Release Diclofenac in Myanmar Healthy Male Volunteers

    Htet Htet Aung


    Full Text Available Background: Sustained release diclofenac (diclofenac SR is the commonly used non-steroidal anti-inflammatory drug for chronic inflammatory conditions such as rheumatoid arthritis. Misoprostol, prostaglandin analogue, is the agent that enhances gastrointestinal mucosal defense. Concomitant administration of misoprostol with diclofenac SR can prevent the gastrointestinal side effects of diclofenac SR. Objective: The purpose of the study was to explore the effect of misoprostol on the pharmacokinetics of diclofenac SR in healthy volunteers. Methods: Crossover study was evaluated in 14 male volunteers. Single oral dose of 100 mg diclofenac SR was concomitantly administered with 200 μg misoprostol with one-week wash out period. Plasma concentrations at 0, 0.5, 1, 1.5, 2, 3, 6 and 10 hrs were determined by high performance liquid chromatography (HPLC. Pharmacokinetic parameters such as area under concentration-time curve (AUC0-α, peak plasma concentration (Cmax, time to achieve peak plasma concentration (Tmax, absorption half-life (T½(ab, elimination half-life (T1/2(el, absorption rate constant (Kab, and elimination rate constant (Kel were determined. Results: With misoprostol, the mean AUC0-α of diclofenac SR was significantly reduced from 12.11±5.25μg/ mL×hr to 4.17±2.72μg/mL×hr (p0.05. The mean T½(ab was decreased from 0.56±0.23hr to 0.54±0.19hr (p>0.05. The mean Kab were almost the same 1.43±0.54hr-1 and 1.43±0.48hr-1. The mean T1/2(el was decreased from 3.68±1.64hr to 3.03±1.08hr (p>0.05. The mean Kel was increased from 0.21±0.09hr-1 to 0.25±0.09hr-1 (p>0.05. Conclusion: There was a significant reduction in the extent of absorption of diclofenac SR when concomitantly administered with misoprostol. Therefore, the dose of diclofenac SR may need to be increased to avoid therapeutic failure of diclofenac SR or concurrent use with misoprostol may need to be changed to other gastroprotective agents.

  2. Effect of dairy manure rate and the stabilization time of amended soils on atrazine degradation.

    Aguilera, Paula; Briceño, Gabriela; Candia, Maribel; Mora, Maria de la Luz; Demanet, Rolando; Palma, Graciela


    The application rate of liquid cow manure (LCM) in the field and the stabilization time of amended soils before application of pre-plant herbicides are factors that determine their efficiency. This study includes evaluation of residual atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) in soil and amended soils with equivalent rate of 100,000; 200,000; and 300,000 L ha(-1) of LCM and the effect of pre-incubation time of amended soils on atrazine degradation. The study was carried out under controlled conditions using an Andisol with previous historical application of atrazine. The respiratory activity and fluorescein diacetate (FDA) studies indicated that the time necessary for stabilization of amended soils is over 20-30 d. During the measurement of respiratory and FDA activity, no significant differences were observed when atrazine was applied. The half-life of atrazine ranged from 5 to 8d and the relative distribution of degradation products seem to be affected by the application of LCM. The pre-incubation time of amended soil and LCM dose would not affect atrazine degradation rate, when the soil has a history of herbicide application. However, repeated applications of LCM in a long period of time could change the soil pH and increase the content of dissolved organic carbon (DOC) which could further contribute to a faster degradation of atrazine. Both effects would reduce the effectiveness of atrazine in weed control.

  3. Pharmacokinetic-pharmacodynamic relationships of cognitive and psychomotor effects of intravenous buprenorphine infusion in human volunteers.

    Jensen, Mette L; Sjøgren, Per; Upton, Richard N; Foster, David J R; Bonde, Peter; Graae, Christian; Skram, Ulrik; Stevner, Lene; Christrup, Lona L


    The main objective of the present study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of the effects of buprenorphine on cognitive functioning in healthy volunteers. Twenty-three male volunteers received 0.6 mg buprenorphine as an intravenous infusion over 150 min. The cognitive and psychomotor performance was evaluated before and at various times after drug administration by a test battery consisting of trail-making test for visual information processing, finger-tapping test for psychomotor speed, and continuous reaction time for attention. Non-linear mixed effect modelling was used in the analysis of the PK/PD relationships. Buprenorphine caused significant deficits in cognitive and psychomotor functioning. The time course of cognitive and psychomotor impairment was found to have a slow distribution to the biophase from plasma with PK/PD models involving an effect compartment providing the best descriptions of the time course of the data. The values for half-life of biophase equilibration were consistent between the neuropsychological tests in the range of 66.6-84.9 min. The time to onset and duration of the cognitive and psychomotor impairment of buprenorphine was determined by a slow distribution to the biophase.

  4. Enhanced acute anti-inflammatory effects of CORM-2-loaded nanoparticles via sustained carbon monoxide delivery.

    Qureshi, Omer Salman; Zeb, Alam; Akram, Muhammad; Kim, Myung-Sic; Kang, Jong-Ho; Kim, Hoo-Seong; Majid, Arshad; Han, Inbo; Chang, Sun-Young; Bae, Ok-Nam; Kim, Jin-Ki


    The aim of this study was to enhance the anti-inflammatory effects of carbon monoxide (CO) via sustained release of CO from carbon monoxide-releasing molecule-2-loaded lipid nanoparticles (CORM-2-NPs). CORM-2-NPs were prepared by hot high pressure homogenization method using trilaurin as a solid lipid core and Tween 20/Span 20/Myrj S40 as surfactant mixture. The physicochemical properties of CORM-2-NPs were characterized and CO release from CORM-2-NPs was assessed by myoglobin assay. In vitro anti-inflammatory effects were evaluated by nitric oxide assay in lipopolysaccharide-stimulated RAW 264.7 macrophages. In vivo anti-inflammatory activity was investigated by measuring paw volumes and histological examination in carrageenan-induced rat paw edema. Spherical CORM-2-NPs were around 100nm with narrow particle size distribution. The sustained CO release from CORM-2-NPs was observed and the half-life of CO release increased up to 10 times compared with CORM-2 solution. CORM-2-NPs showed enhanced in vitro anti-inflammatory effects by inhibition of nitric oxide production. Edema volume in rat paw was significantly reduced after treatment with CORM-2-NPs. Taken together, CORM-2-NPs have a great potential for CO therapeutics against inflammation via sustained release of CO. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Neuroprotective Effects of 7, 8-dihydroxyflavone on Midbrain Dopaminergic Neurons in MPP+-treated Monkeys

    He, Jingjing; Xiang, Zheng; Zhu, Xiaoqing; Ai, Zongyong; Shen, Jingsong; Huang, Tianzhuang; Liu, Liegang; Ji, Weizhi; Li, Tianqing


    Parkinson’s disease (PD) is one common neurodegenerative disease caused by a significant loss of midbrain dopaminergic neurons. Previous reports showed that 7, 8- dihydroxyflavone (7, 8-DHF) as a potent TrkB agonist can mimic BDNF and play neuroprotective roles for mouse dopaminergic neurons. Nonetheless, the safety and neuroprotective effects are unclear in monkey models of PD. Here, we find that 7, 8-DHF could be absorbed and metabolized into 7-hydroxy-8-methoxyflavone through oral administration in monkeys. The half-life time of 7, 8-DHF in monkey plasma is about 4–8 hrs. Furthermore, these monkeys maintain health state throughout the course of seven-month treatments of 7, 8-DHF (30 mg/kg/day). Importantly, 7, 8-DHF treatments can prevent the progressive degeneration of midbrain dopaminergic neurons by attenuating neurotoxic effects of MPP+ and display strong neuroprotective effects in monkeys. Our study demonstrates that this promising small molecule may be transited into a clinical useful pharmacological agent. PMID:27731318

  6. Stereoselective pharmacokinetics of stiripentol: an explanation for the development of tolerance to anticonvulsant effect.

    Arends, R H; Zhang, K; Levy, R H; Baillie, T A; Shen, D D


    An earlier pharmacodynamic study of the chiral antiepileptic drug stiripentol in an intravenous pentylenetetrazol-induced seizure model in the rat showed the development of a significant degree of tolerance to the anticonvulsant and neurotoxic effects following subacute treatment with the racemic compound. A more recent study with the pure enantiomers of stiripentol indicated that the (+)-enantiomer is 2.4 times more potent than the (-)-enantiomer, based on a comparison of brain EC50 values for the anticonvulsant effect. Moreover, (-)-stiripentol has a much longer elimination half-life than (+)-stiripentol. We have re-analyzed the brain and blood samples from the first pharmacodynamic study using a newly developed chiral HPLC assay to investigate whether the tolerance phenomenon with racemic stiripentol was due to a shift in the enantiomeric composition of stiripentol in brain tissue during repetitive administration of racemic drug. A large increase, as much as 5-6-fold, in the (-)/(+) ratio in brain concentration of stiripentol was observed after subacute administration, as compared with that after a single dose of the racemic drug. The enrichment in the less potent enantiomers during repetitive drug administration explains the previous observation of an apparent development of tolerance when the pharmacologic effects were related to total [(-)+(+)] brain concentrations of stiripentol as measured by a non-stereoselective assay. The results of this study highlight the importance of stereoselective pharmacokinetics in investigating the pharmacodynamics of the racemic mixture of a chiral anticonvulsant.

  7. The combined effect of encapsulating curcumin and C6 ceramide in liposomal nanoparticles against osteosarcoma.

    Dhule, Santosh S; Penfornis, Patrice; He, Jibao; Harris, Michael R; Terry, Treniece; John, Vijay; Pochampally, Radhika


    This study examines the antitumor potential of curcumin and C6 ceramide (C6) against osteosarcoma (OS) cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Three liposomal formulations were prepared: curcumin liposomes, C6 liposomes and C6-curcumin liposomes. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with curcumin liposomes alone. Importantly, C6-curcumin liposomes were found to be less toxic on untransformed primary human cells (human mesenchymal stem cells) in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. The efficiency of the preparations was tested in vivo using a human osteosarcoma xenograft assay. Using pegylated liposomes to increase the plasma half-life and tagging with folate (FA) for targeted delivery in vivo, a significant reduction in tumor size was observed with C6-curcumin-FA liposomes. The encapsulation of two water insoluble drugs, curcumin and C6, in the lipid bilayer of liposomes enhances the cytotoxic effect and validates the potential of combined drug therapy.

  8. KR-62980: a novel peroxisome proliferator-activated receptor gamma agonist with weak adipogenic effects.

    Kim, Kwang Rok; Lee, Jeong Hyung; Kim, Seung Jun; Rhee, Sang Dal; Jung, Won Hoon; Yang, Sung-Don; Kim, Sung Soo; Ahn, Jin Hee; Cheon, Hyae Gyeong


    The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is the target for the anti-diabetic drugs including thiazolidinediones. We report here the identification and characterization of a novel PPARgamma agonist KR-62980. KR-62980 acted as a selective PPARgamma agonist in transactivation assay with an EC50 of 15 nM. In fully differentiated 3T3-L1 adipocytes, KR-62980 induced [3H]-deoxyglucose uptake in a concentration-dependent manner in the presence of insulin. KR-62980 was weakly adipogenic with little induction of aP2 mRNA, and was able to antagonize the adipogenic effects of rosiglitazone in C3H10T1/2 cells. In vivo pharmacokinetic profile of KR-62980 revealed that the compound exhibited good oral bioavailability of 65% with a terminal elimination half-life of 2.5 h in the rat. Treatment of high fat diet-induced C57BL/6J mice with KR-62980 for 14 days reduced plasma glucose levels with little side effects with regard to weight gain, cardiac hypertrophy and hepatotoxicity. These results suggest that KR-62980 acts as a selective PPARgamma modulator with anti-hyperglycemic activity, and that the mechanism of actions of KR-62980 appears to be different from that of rosiglitazone with improved side effect profiles.

  9. Effect of BMP-2 Delivery Mode on Osteogenic Differentiation of Stem Cells

    Kim, Yong-Jin; Kim, Ki-Suk; Jang, Hyon-Seok; Chung, Hyung-Min


    Differentiation of stem cells is an important strategy for regeneration of defective tissue in stem cell therapy. Bone morphogenetic protein-2 (BMP-2) is a well-known osteogenic differentiation factor that stimulates stem cell signaling pathways by activating transmembrane type I and type II receptors. However, BMPs have a very short half-life and may rapidly lose their bioactivity. Thus, a BMP delivery system is required to take advantage of an osteoinductive effect for osteogenic differentiation. Previously, BMP delivery has been designed and evaluated for osteogenic differentiation, focusing on carriers and sustained release system for delivery of BMPs. The effect of the delivery mode in cell culture plate on osteogenic differentiation potential was not evaluated. Herein, to investigate the effect of delivery mode on osteogenic differentiation of BM-MSCs in this study, we fabricated bottom-up release and top-down release systems for culture plate delivery of BMP-2. And also, we selected Arg-Gly-Asp- (RGD-) conjugated alginate hydrogel for BMP-2 delivery because alginate is able to release BMP-2 in a sustained manner and it is a biocompatible material. After 7 days of culture, the bottom-up release system in culture plate significantly stimulated alkaline phosphate activity of human bone marrow-mesenchymal stem cells. The present study highlights the potential value of the tool in stem cell therapy. PMID:28197209

  10. Effects of Peripheral Neurotensin on Appetite Regulation and Its Role in Gastric Bypass Surgery.

    Ratner, Cecilia; Skov, Louise J; Raida, Zindy; Bächler, Thomas; Bellmann-Sickert, Kathrin; Le Foll, Christelle; Sivertsen, Bjørn; Dalbøge, Louise S; Hartmann, Bolette; Beck-Sickinger, Annette G; Madsen, Andreas N; Jelsing, Jacob; Holst, Jens J; Lutz, Thomas A; Andrews, Zane B; Holst, Birgitte


    Neurotensin (NT) is a peptide expressed in the brain and in the gastrointestinal tract. Brain NT inhibits food intake, but the effects of peripheral NT are less investigated. In this study, peripheral NT decreased food intake in both mice and rats, which was abolished by a NT antagonist. Using c-Fos immunohistochemistry, we found that peripheral NT activated brainstem and hypothalamic regions. The anorexigenic effect of NT was preserved in vagotomized mice but lasted shorter than in sham-operated mice. This in combination with a strong increase in c-Fos activation in area postrema after ip administration indicates that NT acts both through the blood circulation and the vagus. To improve the pharmacokinetics of NT, we developed a pegylated NT peptide, which presumably prolonged the half-life, and thus, the effect on feeding was extended compared with native NT. On a molecular level, the pegylated NT peptide increased proopiomelanocortin mRNA in the arcuate nucleus. We also investigated the importance of NT for the decreased food intake after gastric bypass surgery in a rat model of Roux-en-Y gastric bypass (RYGB). NT was increased in plasma and in the gastrointestinal tract in RYGB rats, and pharmacological antagonism of NT increased food intake transiently in RYGB rats. Taken together, our data suggest that NT is a metabolically active hormone, which contributes to the regulation of food intake.

  11. Determination of sulfosulfuron residues in soil under wheat crop by a novel and cost-effective method and evaluation of its carryover effect.

    Singh, Shashi B; Kulshrestha, Gita


    A novel and cost-effective method of sulfosulfuron extraction has been developed using distilled water as an extraction solvent. Using this method, the environmental fate of sulfosulfuron was investigated in soil under wheat crop. Studies were conducted under natural field conditions in randomized block design and herbicide (75% water dispersible granules (WG)) was applied after 24 days of sowing. The rates of applications were 25 and 50 g of active ingredient (a.i.) per hectare. Soil samples were collected at predetermined intervals and analyzed by high performance liquid chromatography (HPLC). The minimum detection limit was found to be 0.001 micro g g(-1). The dissipation of sulfosulfuron followed first-order rate kinetics and dissipated with a half-life of 5.4-6.3 days. After harvest, field soil was used for conducting a pot experiment with bottle gourd (Lagenaria siceraria) as test plants to study the carry over effect of sulfosulfuron. No phytotoxicity was observed to bottle gourd in pot experiment with harvest soil.

  12. Modelling the biological half-life and seasonality of ¹⁴C in Fucus vesiculosus from the east coast of Ireland: implications for the estimation of future trends.

    Keogh, S M; Cournane, S; León Vintró, L; McGee, E J; Mitchell, P I


    Radiocarbon levels were recorded in Fucus vesiculosus samples collected on a monthly basis over a three-year period at a site on the east coast of Ireland. The resulting data was analysed using a numerical model which estimates the transit times from the Sellafield plant to the sampling location, and the mean availability time of ¹⁴C in seaweed. With the inclusion of a model parameter allowing for seasonal variability in uptake by the Fucus, good correlation was observed between the predicted and measured concentrations. Future temporal trends of ¹⁴C Fucus concentrations along the eastern Irish coastline were modelled with the application of three possible prospective discharge scenarios, predicting ¹⁴C Fucus concentrations to reduce to ambient background levels within 2.5-years of discharges being set to zero. Such projections may prove helpful in assessing the consequences of discharge management and policy making in the context of the OSPAR convention.

  13. In the eye of the storm. Planned EEG amendments reduce the half-life of the market survey of complete PV power generation systems; Im Auge des Wirbelsturms. Die EEG-Reformplaene lassen die Halbwertszeit der Marktuebersicht Komplettsysteme rapide schrumpfen

    Krause, Matthias B.


    The impending amendments of the German Renewables Act (EEG) have put the photovoltaic industry in a state of fright. Accurate market surveys are hardly possible, although at least a return on investments will still be possible even after 2012.

  14. Analysis on the Changes of the Journal Half Life in the Science JCR%JCR自然科学版期刊半衰期指标的区间变化分析

    党亚茹; 王莉亚



  15. 互引期刊群中出版延时对被引半衰期的影响%The influence of the publication delay on journal cited half-life in an inter-citation journal group

    于光; 郭蕊



  16. Association of lipoprotein(a), prostaglandin I(2)--synthesis stimulating plasma factor, biological half-life of prostaglandin I(2)and high-density lipoproteins in HIV-1 infection of different stages.

    Kritz, H; Efthimiou, Y; Stamatopoulos, J; Najemnik, C; Sinzinger, H


    Patients with human immunodeficiency virus show increased atheroembolism and premature arterial events (stroke, myocardial infarction), but no increased venous thromboembolism. This paper describes an association of elevated lipoprotein(a), a decreased prostaglandin I(2)(PGI(2)) synthesis stimulating plasma factor, diminished PGI(2)-stability in plasma and decreased high-density lipoprotein-cholesterol and apolipoprotein A. It is unclear to what extent these biochemical findings represent an acute phase reaction only or a disturbance in the prostaglandin system. Definitely, they are resulting in severe hemostatic imbalance decreasing local PGI(2)-availability with a dramatic reduction in the cytoprotective capacity favouring the onset of premature arterial events seen in some of the patients. Copyright 2000 Harcourt Publishers Ltd.

  17. Non-monotonous half-life growth model for Internet topology%面向互联网拓扑的非单调半程增长模型

    张昕; 李晓光; 宋宝燕


    互联网拓扑模型的构造,是网络进一步应用和发展的重要研究基础.在现有建模方法中,构成拓扑的节点和连接均为单调增长,显然无法体现网络的真实演化.通过分析长时间跨度的网络实测数据,提取出网络拓扑中节点和连接的消亡与新生规律.在此基础上,进一步修正了拓扑增长的优先倾向概率,并给出一种新的非单调增长的互联网拓扑模型.实验结果说明,在多项重要拓扑特征量方面,该模型均可以很好地体现互联网的动态演化过程.%The explosive applications of Internet stimulate the research on the structure evolution of networks involved. The available methods only add entities and connections to the existing networks, which is totally unrealistic since the real Internet is dynamic due to the new equipments deletion and add. To attack this issue, it presents an algorithm that can take into consideration the dynamics in Internet via a preferential tendency probability of topology, in which time series, nodes life are included. The experimental results demonstrate that the algorithm is more realistic than traditional ones, particularly in the dynamic evolution of the Internet.

  18. Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

    Steinbach, Christoph, E-mail: [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Fedorova, Ganna [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Prokes, Miroslav [Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, v.v.i., Kvetna 8, 603 65 Brno (Czech Republic); Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic)


    Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L{sup −1} to μg L{sup −1}. In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC{sub 50} values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L{sup −1} for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L{sup −1}. Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L{sup −1} of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of

  19. Doxycycline down-regulates DNA-PK and radiosensitizes tumor initiating cells: Implications for more effective radiation therapy.

    Lamb, Rebecca; Fiorillo, Marco; Chadwick, Amy; Ozsvari, Bela; Reeves, Kimberly J; Smith, Duncan L; Clarke, Robert B; Howell, Sacha J; Cappello, Anna Rita; Martinez-Outschoorn, Ubaldo E; Peiris-Pagès, Maria; Sotgia, Federica; Lisanti, Michael P


    DNA-PK is an enzyme that is required for proper DNA-repair and is thought to confer radio-resistance in cancer cells. As a consequence, it is a high-profile validated target for new pharmaceutical development. However, no FDA-approved DNA-PK inhibitors have emerged, despite many years of drug discovery and lead optimization. This is largely because existing DNA-PK inhibitors suffer from poor pharmacokinetics. They are not well absorbed and/or are unstable, with a short plasma half-life. Here, we identified the first FDA-approved DNA-PK inhibitor by "chemical proteomics". In an effort to understand how doxycycline targets cancer stem-like cells (CSCs), we serendipitously discovered that doxycycline reduces DNA-PK protein expression by nearly 15-fold (> 90%). In accordance with these observations, we show that doxycycline functionally radio-sensitizes breast CSCs, by up to 4.5-fold. Moreover, we demonstrate that DNA-PK is highly over-expressed in both MCF7- and T47D-derived mammospheres. Interestingly, genetic or pharmacological inhibition of DNA-PK in MCF7 cells is sufficient to functionally block mammosphere formation. Thus, it appears that active DNA-repair is required for the clonal expansion of CSCs. Mechanistically, doxycycline treatment dramatically reduced the oxidative mitochondrial capacity and the glycolytic activity of cancer cells, consistent with previous studies linking DNA-PK expression to the proper maintenance of mitochondrial DNA integrity and copy number. Using a luciferase-based assay, we observed that doxycycline treatment quantitatively reduces the anti-oxidant response (NRF1/2) and effectively blocks signaling along multiple independent pathways normally associated with stem cells, including STAT1/3, Sonic Hedgehog (Shh), Notch, WNT and TGF-beta signaling. In conclusion, we propose that the efficacy of doxycycline as a DNA-PK inhibitor should be tested in Phase-II clinical trials, in combination with radio-therapy. Doxycycline has excellent

  20. Effect

    M.F. Sabry; M.R. Hamed; El Sayed, M.E.


    Stress alters psychological diseases such as anxiety and depression. Protein malnutrition (PM) contributes to psychological disorders. The present study aimed to investigate the effect of biphenyl dimethyl dicarboxylate (DDB) on anxiety of psychologically stressed protein malnourished mice as compared to its effect in normally-fed mice. Fluoxetine (FLX) was used as reference standard. Animals were randomly divided into two major groups, normally-fed group provided with 20% casein diet and a p...

  1. Organic stealth nanoparticles for highly effective in vivo near-infrared photothermal therapy of cancer.

    Cheng, Liang; Yang, Kai; Chen, Qian; Liu, Zhuang


    In recent years, a wide range of near-infrared (NIR) light absorbing nanomaterials, mostly inorganic ones, have been developed for photothermal therapy (PTT) of cancer. In this work, we develop a novel organic PTT agent based on poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS), a conductive polymer mixture with strong NIR absorbance, for in vivo photothermal treatment of cancer. After being layer-by-layer coated with charged polymers and then conjugated with branched polyethylene glycol (PEG), the obtained PEDOT:PSS-PEG nanoparticles are highly stable in the physiological environment and exhibit a stealth-like behavior after intravenous injection with a long blood circulation half-life. As a result, an extremely high in vivo tumor uptake of PEDOT:PSS-PEG attributed to the tumor-enhanced permeability and retention effect is observed. We further use PEDOT:PSS-PEG as a PTT agent for in vivo cancer treatment and realize excellent therapeutic efficacy in a mouse tumor model under NIR light irradiation at a low laser power density. Comprehensive blood tests and careful histological examination reveal no apparent toxicity of PEDOT:PSS-PEG to mice at our treated dose within 40 days. To our best knowledge, this work is the first to use systemically administrated conductive polymer nanoparticles for highly effective in vivo PTT treatment in animals and encourages further explorations of those organic nanomaterials for cancer theranostic applications.

  2. Nanoprecipitated catestatin released from pharmacologically active microcarriers (PAMs) exerts pro-survival effects on MSC.

    Angotti, C; Venier-Julienne, M C; Penna, C; Femminò, S; Sindji, L; Paniagua, C; Montero-Menei, C N; Pagliaro, P


    Catestatin (CST), a fragment of Chromogranin-A, exerts angiogenic, arteriogenic, vasculogenic and cardioprotective effects. CST is a very promising agent for revascularization purposes, in "NOOPTION" patients. However, peptides have a very short half-life after administration and must be conveniently protected. Fibronectin-coated pharmacologically active microcarriers (FN-PAM), are biodegradable and biocompatible polymeric microspheres that can convey mesenchymal stem cell (MSCs) and therapeutic proteins delivered in a prolonged manner. In this study, we first evaluated whether a small peptide such as CST could be nanoprecipitated and incorporated within FN-PAMs. Subsequently, whether CST may be released in a prolonged manner by functionalized FN-PAMs (FN-PAM-CST). Finally, we assessed the effect of CST released by FN-PAM-CST on the survival of MSCs under stress conditions of hypoxia-reoxygenation. An experimental design, modifying three key parameters (ionic strength, mixing and centrifugation time) of protein nanoprecipitation, was used to define the optimum condition for CST. An optimal nanoprecipitation yield of 76% was obtained allowing encapsulation of solid CST within FN-PAM-CST, which released CST in a prolonged manner. In vitro, MSCs adhered to FN-PAMs, and the controlled release of CST from FN-PAM-CST greatly limited hypoxic MSC-death and enhanced MSC-survival in post-hypoxic environment. These results suggest that FN-PAM-CST are promising tools for cell-therapy.

  3. Lacosamide as treatment for partial epilepsy: mechanisms of action, pharmacology, effects, and safety

    Christoph Kellinghaus


    Full Text Available Christoph KellinghausDepartment of Neurology, Klinikum Osnabrück, GermanyAbstract: Lacosamide (LCM is a novel agent that has been developed as an antiepileptic drug. In vitro studies suggest that LCM modulates voltage-gated sodium channels by enhancing their slow inactivation. In addition, LCM seems to interact with collapsin-response mediator protein 2 and thus may mediate neuronal plasticity. LCM has an elimination half-life of 13 hours, no relevant protein binding, and does not induce or inhibit enzymes of the cytochrome P450 system. No clinically significant drug–drug interactions have been discovered as yet. Experimental data suggest anticonvulsant as well as analgesic effects. Large clinical studies have demonstrated its efficacy for treatment of patients with partial seizures. LCM is well tolerated, and the most common adverse events are unspecific central nervous system and gastrointestinal effects such as dizziness, vertigo, nausea, and headache. LCM is approved for treatment of partial seizures with or without secondary generalization in the United States and the European Union within a dose range of 200 to 400 mg per day, administered twice daily. In addition to the oral formulations, an intravenous infusion solution is available.Keywords: lacosamide, epilepsy, antiepileptic drug

  4. Effects of transforming growth interacting factor on biological behaviors of gastric carcinoma cells

    Zhong-Liang Hu; Ji-Fang Wen; De-Sheng Xiao; Hui Zhen; Chun-Yan Fu


    AIM:Transforming growth interacting factor (TGIF) is an inhibitor of both transforming growth factor β (TGF-β) and retinoid signaling pathways. Moreover, the activation of MAPK pathway can prolong its half-life. However, its role in carcinogenesis is still unknown. Thus we attempted to investigate the effect of TGIF on biologic behaviors of gastric carcinoma cells.METHODS: Gastric carcinoma cell line, SGC-7901, was stably transfected with plasmid PcDNA3.1-TGIF. Western blotting and cell immunohistochemistry screening for the highly expressing clone of TGIF were employed. The growth of transfected cells was investigated by MTT and colonyformation assays, and apoptosis was measured by flow cytometry (FCM) and transmission electron microscopy.Tumorigenicity of the transfectant cells was also analyzed.RESULTS: TGIF had no effect on the proliferation, cell cycle and apoptosis of SGC-7901 cells, but cellular organelles of cells transfected with TGIF were richer than those of vector control or parental cells. Its clones were smaller than the control ones in plate efficiency, and its tumor tissues also had no obvious necrosis compared with the vector control or parental cells. Moreover, TGIF could resist TGF-β mediated growth inhibition.CONCLUSION: TGIF may induce differentiation of stomach neoplastic cells. In addition, TGIF can counteract the growth inhibition induced by TGF-β.

  5. The pharmacokinetics and physiological effects of buprenorphine infusion in premature neonates.

    Barrett, D A; Simpson, J; Rutter, N; Kurihara-Bergstrom, T; Shaw, P N; Davis, S S


    1. The pharmacokinetics and physiological effects of buprenorphine were studied in 12 newborn premature neonates (27 to 32 weeks gestational age) who were given a loading dose of 3.0 micrograms kg-1 of buprenorphine followed by an intravenous infusion of 0.72 micrograms kg-1 h-1 of buprenorphine. Plasma concentrations of buprenorphine were measured during the infusion, at steady-state and for 24 h after the cessation of the buprenorphine infusion. 2. The mean steady-state plasma buprenorphine concentration (+/- s.d.) for an infusion rate of 0.72 micrograms kg-1 h-1 was 4.3 +/- 2.6 ng ml-1. 3. Buprenorphine clearance was 0.23 +/- 0.07 l h-1 kg-1, the elimination half-life was 20 +/- 8 h and the volume of distribution was 6.2 +/- 2.11 l kg-1. 4. Small but significant falls were noted in systolic blood pressure at 6 h and heart rate at 1, 6 and 12 h after the administration of buprenorphine, but these did not appear to cause any clinical deterioration. 5. Four of the 12 subjects studied required an increase in the infusion rate of buprenorphine to achieve adequate sedation. 6. The results suggest that this dosing regimen of buprenorphine is safe but may not be as effective as other opioids in producing sedation and analgesia in premature newborns.

  6. Non-target effects of pretilachlor on microbial properties in tropical rice soil.

    Sahoo, Subhashree; Adak, Totan; Bagchi, Torit B; Kumar, Upendra; Munda, Sushmita; Saha, Sanjoy; Berliner, J; Jena, Mayabini; Mishra, B B


    The use of herbicides has been questioned in recent past for their non-target effects. Therefore, we planned to study the effect of pretilachlor on growth and activities of microbes in tropical rice soil under controlled condition at National Rice Research Institute, Cuttack, India. Three pretilachlor treatments, namely, recommended dose at 600 g a.i. ha(-1) (RD), double the recommended dose at 1200 g a.i. ha(-1) (2RD), and ten times of the recommended dose at 6000 g a.i. ha(-1) (10RD) along with control, were imposed. The initial residue (after 2 h of spray) deposits in soil were 0.174, 0.968, and 3.35 μg g(-1) for recommended, double the recommended, and ten times of the recommended doses, respectively. No residue in soil was detected in RD treatment on day 45. The half life values were 16.90, 17.76, and 36.47 days for RD, 2RD, and 10RD treatments, respectively. Application of pretilachlor at 10RD, in general, had significantly reduced the number of bacteria, actinomycetes, fungi, nitrogen fixers, and microbial biomass carbon. Pretilachlor at RD did not record any significant changes in microbial properties compared to control. The results of the present study thus indicated that pretilachlor at RD can be safely used for controlling grassy weeds in rice fields.

  7. Effects of repeated applications of fungicide carbendazim on its persistence and microbial community in soil

    YU Yunlong; CHU Xiaoqiang; PANG Guohui; XIANG Yueqin; FANG Hua


    Carbendazim, a systemic benzimidazole fungicide, is applied repeatedly to control of plant diseases including soilborne diseases, over a growing season. Studies were carried out under laboratory conditions to assess the effects of repeated carbendazim applications on its persistence and microbial community in soil. The results indicate that dissipation of carbendazim in soil was accelerated with its application frequency. The degradation rate constant of carbendazim was increased significantly from 0.074 d-1 to 0.79 d-1. The corresponding half-life was shorten markedly from 9.3 d to 0.9 d after four repeated applications. No significant inhibitory effect of carbendazim on soil microbial utilization of the carbon sources was observed after first treatment, but a slight increase in average well color development (AWCD) was shown after second, third, and fourth applications. It suggested that soil microorganisms become adapted to carbendazim after repeated application. Simpson and Shannon indexes of soil microbial community from carbendazim treated soil were also similar to those from the control soil, indicating that the richness and dominant character of soil microorganisms remain unchangeable after repeated application. However, after first, second, and third addition of carbendazim, McIntosh indexes on day 21 were significantly increased as compared with the control, suggesting that balance of soil microorganisms was altered due to the enrichment of the specific carbendazim-adapting strains in soil.

  8. [Plasma pharmacokinetics of roxatidine in the healthy man: correlation with gastric antisecretory effect].

    Chen, W W; Kolsky, H; Lewin, M J; Bonfils, S


    Inhibitory effects of roxatidine acetate upon human gastric secretion have been shown to be dose-related after oral administration. In order to correlate this effect with drug pharmacokinetics, blood concentration of the active metabolite, roxatidine, was assessed in 10 healthy volunteers, each receiving in random order 75, 150, 300, 600 mg of roxatidine acetate and placebo. Blood was drawn for roxatidine measurement at T 0 (time of drug intake) T 75, 90, 120, 150, 210, 240 and 300 min. Meal-induced gastric secretion was studied by intragastric titration (IGT) at 15 min intervals, from T 150 to T 240. Mean peak of blood concentration occurred at T 150 with significant correlation with the administered dosage. Gastric secretion inhibition over the 90 min of IGT correlated with peak concentration exclusively for the subpopulation with peak occurrence at T 150. Beyond the peak, decrease in roxatidine concentrations was slow, as expected from a known 6-h half-life. However, overall results showed that mean blood concentration was correlated with gastric secretion inhibition from T 180 on. The last IGT sample also correlated with the peak. Interpretation of these results would be different whether roxatidine concentration variations are appreciated as exhibiting a significant decrease or not. Infusion studies of roxatidine would be a valuable technique for further analysis and comparison of blood-concentration/efficacy relationships as compared with other H2-antagonists.

  9. Phosphate buffer effects on thermal stability and H2O2-resistance of horseradish peroxidase.

    Asad, Sedigheh; Torabi, Seyed-Fakhreddin; Fathi-Roudsari, Mehrnoosh; Ghaemi, Nasser; Khajeh, Khosro


    Horseradish peroxidase (HRP) has attracted intense research interest due to its potential applications in biotechnological fields. However, inadequate stability under prevalent conditions such as elevated temperatures and H(2)O(2) exposure, has limited its industrial application. In this study, stability of HRP was investigated in the presence of different buffer systems (potassium phosphate and Tris-HCl) and additives. It was shown that the concentration of phosphate buffer severely affects enzyme thermostability in a way that in diluted potassium phosphate buffer (10mM) half-life (from 13 to 35 min at 80 °C) and T(m) (from 73 to 77.5 °C) increased significantly. Among additives tested, trehalose had the most thermostabilizing effect. Exploring the role of glycosylation in stabilizing effect of phosphate buffer, non-glycosylated recombinant HRP was also examined for its thermal and H(2)O(2) stability in both diluted and concentrated phosphate buffers. The recombinant enzyme was more thermally stable in diluted buffer in accordance to glycosylated HRP; but interestingly recombinant HRP showed higher H(2)O(2) tolerance in concentrated buffer.

  10. Surfactant effect on persistence of oxadiazolyl 3(2H)-pyridazinones against Pseudaletia separata walker.

    Huang, Qingchun; Wu, Jihua; Kong, Yuping; Liu, Manhui; Cao, Song


    The photodynamic decomposition of two new insect-growth inhibitors (IGRs), 2-tert-butyl-5-[5'-aryl-2'-(1',3',4'-oxadiazolyl)methoxy]-3(2H)-pyridazinones (OPB) and its 4-chloro substituted derivative (OPC), and effect of surfactants on persistence of their bioactivity were taken into investigation. Both chemicals were significantly induced to photolysis by ultraviolet light at 365 nm wavelength and their inhibitory activities against Pseudaletia separata larvae decreased with the increasing irradiation time. However, irradiation at 254 nm wavelength didn't cause their photodegradation. Triton X-100 and Succinic-sulfonie acidic sodium but not Tween 60 possessed strong capability to slow down the decomposition and obviously prolonged the half life of OPC in laboratory and field whilst effects of the three surfactants almost did not preserve the inhibitory activity of OPB. Data suggested that electron-withdrawing halogen (-Cl) on the pi electron system in planar benzene-oxadialyl structures might reduce the efficiency of OPC on ultraviolet (UV) photoabsorption, and its hydrophobic interaction with the surfactants might be beneficial for forming stable micellar solubilization, thus sustaining the chemical's bioactivity.

  11. The isolation of nuclear envelopes. Effects of thiol-group oxidation and of calcium ions.

    Comerford, S A; McLuckie, I F; Gorman, M; Scott, K A; Agutter, P S


    The effects of (a) oxidative cross-linking of protein thiol groups and (b) the presence or absence of Ca2+ ions on rat liver nuclear-envelope isolation were studied. Two envelope-isolation procedures were compared: a well characterized low-ionic-strength method and a recently developed high-ionic-strength method. The latter method seems preferable to the former in respect of lower intranuclear contamination of the envelopes, suppression of endogenous serine proteinase, and maintenance of high specific activities of envelope-associated enzymes. In both procedures, however, the presence of Ca2+ gave rise to a rapid, apparently irreversible, contamination of the envelopes by intranuclear material. This effect was half-maximal at 20 microM-Ca2+. In addition, the envelopes became contaminated with intranuclear material by a Ca2+-independent mechanism, apparently resulting from N-ethylmaleimide-sensitive intermolecular disulphide-bond formation. This oxidative process seemed to have two major kinetic components (half-life, t1/2, approx. 2 min and 10 min). In view of these findings, it is recommended that (i) for most purposes, nuclear envelopes be isolated by the newly developed high-ionic-strength procedure, (ii) irrespective of the method used, Ca2+-chelators be included in all the buffers, (iii) thiol-group oxidation be prevented or reversed during the procedure.

  12. Effects of Activating Mutations on EGFR Cellular Protein Turnover and Amino Acid Recycling Determined Using SILAC Mass Spectrometry

    Michael J. Greig


    Full Text Available Rapid mutations of proteins that are targeted in cancer therapy often lead to drug resistance. Often, the mutation directly affects a drug’s binding site, effectively blocking binding of the drug, but these mutations can have other effects such as changing the protein turnover half-life. Utilizing SILAC MS, we measured the cellular turnover rates of an important non-small cell lung cancer target, epidermal growth factor receptor (EGFR. Wild-type (WT EGFR, EGFR with a single activating mutant (Del 746–750 or L858R, and the drug-resistant double mutant (L858R/T790M EGFR were analyzed. In non-small cell lung cancer cell lines, EGFR turnover rates ranged from 28 hours in A431 cells (WT to 7.5 hours in the PC-9 cells (Del 746–750 mutant. The measurement of EGFR turnover rate in PC-9 cells dosed with irreversible inhibitors has additional complexity due to inhibitor effects on cell viability and results were reported as a range. Finally, essential amino acid recycling (K and R was measured in different cell lines. The recycling was different in each cell line, but the overall inclusion of the effect of amino acid recycling on calculating EGFR turnover rates resulted in a 10–20% reduction in rates.

  13. β-Cyclodextrin-complexed (-)-linalool produces antinociceptive effect superior to that of (-)-linalool in experimental pain protocols.

    Quintans-Júnior, Lucindo J; Barreto, Rosana S S; Menezes, Paula P; Almeida, Jackson R G S; Viana, Ana Flávia S C; Oliveira, Rita C M; Oliveira, Aldeídia P; Gelain, Daniel P; de Lucca Júnior, Waldecy; Araújo, Adriano A S


    Many plants produce (-)-linalool, a plant-derived monoterpene alcohol, including members of the Lamiaceae (mints) and Lauraceae family (laurels, cinnamon, rosewood). The anti-inflammatory and analgesic effects of (-)-linalool have been widely suggested for various studies. Poor chemical stability and short half-life restrain the clinical applications of some essential oil and monoterpenes, including (-)-linalool. However, β-cyclodextrin (β-CD) has been used to increase solubility and stability of lipophilic compounds and also to improve the pharmacological effects. In this study, the antinociceptive effect of (-)-linalool and (-)-linalool/β-CD was examined using the acetic acid writhing reflex, formalin and hotplate tests in rodents. (-)-Linalool and (-)-linalool/β-CD demonstrated strong antinociceptive activity in all the chemical- and heat-induced mice models (p < 0.01 or p < 0.001). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. In peritonitis induced by carrageenan, isolated monoterpene or β-CD complex also reduced total leucocyte migration and TNF-α levels in peritoneal fluid. The inclusion complexes, (-)-linalool/β-CD, revealed that the antinociceptive effect was significantly (p < 0.01) improved when compared with (-)-linalool alone. Such results were unlikely to be provoked by any motor abnormality. Together, our results suggest that β-CD might represent an important tool for improvement of analgesic and anti-inflammatory profiles of (-)-linalool and other water-insoluble compounds, such as lipophilic monoterpenes or essential oils.

  14. Balancing benefits and risks in patients receiving incretin-based therapies: focus on cardiovascular and pancreatic side effects.

    Haluzík, Martin; Mráz, Miloš; Svačina, Štěpán


    Incretin-based therapies either increase endogenous levels of glucagon-like peptide-1 by prolonging its half-life (DPP-4 inhibitors) or directly stimulate its receptor (glucagon-like peptide-1 analogues; GLP-1 RA). They are currently widely used for the treatment of patients with type 2 diabetes mellitus owing to good antidiabetic efficacy, low risk of hypoglycemia, and relatively few other side effects. They also offer potential additional benefits such as weight neutrality or weight loss, positive effects on blood pressure and lipid levels, and potential cardio- and neuroprotectivity. Some experimental and clinical studies have raised concerns with respect to potential cardiovascular and pancreatic side effects of these therapies such as increased risk of heart failure with DPP-4 inhibitors as well as acute pancreatitis and pancreatic cancer with both classes. The available data are at present not robust enough to enable firm conclusions regarding these potential associations. Nevertheless, some recent data suggest a possibility of slightly increased risk of acute pancreatitis with GLP-1 RAs while they do not indicate increased risk of pancreatic cancer. Ongoing cardiovascular outcome trials will shed more light on the possible cardioprotective effects of incretin-based therapies as well as on the possible interconnection of DPP-4 inhibitors and heart failure.

  15. [Preparation and the biological effect of fusion protein GLP-1-exendin-4/ IgG4(Fc) fusion protein as long acting GLP-1 receptor agonist].

    Zheng, Yun-cheng


    GLP-1 has a variety of anti-diabetic effects. However, native GLP-1 is not suitable for treatment of diabetes due to its short half-life (t½, 2-5 min). Exendin-4 is a polypeptide isolated from lizard saliva, which can bind to GLP-1 receptor, produce physiological effects similar to GLP-1, t½ up to 2.5 h, therefore, we developed a long-lasting GLP-1 receptor agonists and GLP-1-exendin-4 fusion IgG4 Fc [GLP-1-exendin-4/ IgG4(Fc)]. We constructed the eukaryotic expression vector of human GLP-1-exendin-4/IgG4(Fc)-pOptiVEC- TOPO by gene recombination technique and expressed the fusion protein human GLP-1-IgG4 (Fc) in CHO/DG44 cells. The fusion protein stimulated the INS-1 cells secretion of insulin, GLP-1, exendin-4 and fusion protein in CD1 mice pharmacokinetic experiments, as well as GLP-1, exendin-4 and fusion protein did anti-diabetic effect on streptozotocin induced mice. Results demonstrated that the GLP-1-exendin-4/IgG4(Fc) positive CHO/DG44 clones were chosen and the media from these positive clones. Western blotting showed that one protein band was found to match well with the predicted relative molecular mass of human GLP-1-exendin-4/IgG4(Fc). Insulin RIA showed that GLP-1-exendin-4/IgG4(Fc) dose-dependently stimulated insulin secretion from INS-1 cells. Pharmacokinetic studies in CD1 mice showed that with intraperitoneal injection (ip), the fusion protein peaked at 30 min in circulation and maintained a plateau for 200 h. Natural biological half-life of exendin-4 was (1.39 ± 0.28) h, GLP-1 in vivo t½ 4 min, indicating that fusion protein has long-lasting effects on the modulation of glucose homeostasis. GLP-1-exendin-4/IgG4(Fc) was found to be effective in reducing the incidence of diabetes in multiple-low-dose streptozotocin-induced diabetes in mice, longer duration of the biological activity of the fusion protein. The biological activity was significantly higher than that of GLP-1 and exendin-4. GLP-1-exendin-4/IgG4(Fc) has good anti-diabetic activity

  16. A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects

    Zhao, Shao-Jun; Wang, De-Hua; Li, Yan-Wei; Han, Lei; Xiao, Xing; Ma, Min; Wan, David Chi-Cheong; Hong, An; Ma, Yi


    A novel neuroendocrine peptide, pituitary adenylate cyclase activating peptide (PACAP), was found to have an important role in carbohydrate or lipid metabolism and was susceptible to dipeptidyl peptidase IV degradation. It can not only mediate glucose-dependent insulin secretion and lower blood glucose by activating VPAC2 receptor, but also raise blood glucose by promoting glucagon production by VPAC1 receptor activation. Therefore, its therapeutic application is restricted by the exceedingly short-acting half-life and the stimulatory function for glycogenolysis. Herein, we generated novel peptide-conjugated selenium nanoparticles (SeNPs; named as SCD), comprising a 32-amino acid PACAP-derived peptide DBAYL that selectively binds to VPAC2, and chitosan-modified SeNPs (SeNPs-CTS, SC) as slow-release carrier. The circulating half-life of SCD is 14.12 h in mice, which is 168.4-and 7.1-fold longer than wild PACAP (~5 min) and DBAYL (~1.98 h), respectively. SCD (10 nmol/L) significantly promotes INS-1 cell proliferation, glucose uptake, insulin secretion, insulin receptor expression and also obviously reduces intracellular reactive oxygen species levels in H2O2-injured INS-1 cells. Furthermore, the biological effects of SCD are stronger than Exendin-4 (a clinically approved drug through its insulinotropic effect), DBAYL, SeNPs or SC. A single injection of SCD (20 nmol/kg) into db/db mice with type 2 diabetes leads to enhanced insulin secretion and sustained hypoglycemic effect, and the effectiveness and duration of SCD in enhancing insulin secretion and reducing blood glucose levels are much stronger than Exendin-4, SeNPs or SC. In db/db mice, chronic administration of SCD by daily injection for 12 weeks markedly improved glucose and lipid profiles, insulin sensitivity and the structures of pancreatic and adipose tissue. The results indicate that SC can play a role as a carrier for the slow release of bioactive peptides and SCD could be a hopeful therapeutic against

  17. A kinematic-based methodology for radiological protection: Runoff analysis to calculate the effective dose for internal exposure caused by ingestion of radioactive isotopes

    Sasaki, Syota; Yamada, Tadashi; Yamada, Tomohito J.


    We aim to propose a kinematic-based methodology similar with runoff analysis for readily understandable radiological protection. A merit of this methodology is to produce sufficiently accurate effective doses by basic analysis. The great earthquake attacked the north-east area in Japan on March 11, 2011. The system of electrical facilities to control Fukushima Daiichi nuclear power plant was completely destroyed by the following tsunamis. From the damaged reactor containment vessels, an amount of radioactive isotopes had leaked and been diffused in the vicinity of the plant. Radiological internal exposure caused by ingestion of food containing radioactive isotopes has become an issue of great interest to the public, and has caused excessive anxiety because of a deficiency of fundamental knowledge concerning radioactivity. Concentrations of radioactivity in the human body and internal exposure have been studied extensively. Previous radiologic studies, for example, studies by International Commission on Radiological Protection(ICRP), employ a large-scale computational simulation including actual mechanism of metabolism in the human body. While computational simulation is a standard method for calculating exposure doses among radiology specialists, these methods, although exact, are too difficult for non-specialists to grasp the whole image owing to the sophistication. In this study, the human body is treated as a vessel. The number of radioactive atoms in the human body can be described by an equation of continuity, which is the only governing equation. Half-life, the period of time required for the amount of a substance decreases by half, is only parameter to calculate the number of radioactive isotopes in the human body. Half-life depends only on the kinds of nuclides, there are no arbitrary parameters. It is known that the number of radioactive isotopes decrease exponentially by radioactive decay (physical outflow). It is also known that radioactive isotopes

  18. On the effects of human galanin in man

    Holst, J J; Bersani, M; Hvidberg, A;


    concentrations in plasma decreased significantly and similarly. Growth hormone levels, however, increased eight-fold during galanin infusions. Galanin was eliminated from plasma with a half-life of 3.7 +/- 0.4 min, similar to that of porcine galanin. It is concluded that human galanin powerfully stimulates...

  19. Clinical Pharmacology of Ciprofloxacin in Neonates: Effects and Pharmacokinetics

    Gian Maria Pacifici


    Full Text Available Ciprofloxacin is the most commonly used fluoroquinolone. Ciprofloxacin is prescribed for 1 in 44 Americans. Ciprofloxacin is a broad-spectrum bactericidal antibiotic, effective against both gram-positive and gram-negative bacteria, being especially active against the Enterobacteriacae, including many microorganisms resistant to penicillins, cephalosporins and aminoglycosides, and also is effective against Haemophilus influenzae, penicillinase-producing Neisseria gonorrhea, Campylobacter and Pseudomonas aeruginosa. Streptococci and pneumococci are weakly inhibited and there is a high incidence of staphylococcal resistance to ciprofloxacin. In neonates, the dose of ciprofloxacin is 10 mg/kg intravenously over 30-60 min infusion, and 20 mg/kg is used to treat Pseudomonas aeruginosa infection. Ciprofloxacin treatment is effective in life-threatening multi-drug resistant Pseudomonas aeruginosa. Ciprofloxacin may be administered by mouth and has a bioavailability of 70% and is mainly recovered unchanged in the urine. Ciprofloxacin is safe and well tolerated in infants. In neonates, the half-life of ciprofloxacin is 3-4 hours. For meningococcal prophylaxis, give a single dose of 30 mg/kg (up to a maximum of 125 mg orally. Ciprofloxacin is active against Citrobacter kosery that produces brain abscesses. The mortality rate for meningitis due to Citrobacter kosery is approximately 30%. Third-generation cephalosporins and aminoglycosides failed to prevent the high rates of morbidity and mortality caused by Citrobacter infections. Ciprofloxacin is the antibiotic treatment option for systemic infection or meningitis caused by Citrobacter kosery. Ciprofloxacin has been used to treat neonatal pneumonia, meningitis, and septicemia and was effective in all cases. The aim of this study is to review the clinical pharmacology of ciprofloxacin in neonates.

  20. Age-dependent pharmacokinetics and effect of roscovitine on Cdk5 and Erk1/2 in the rat brain.

    Sallam, Hatem; Jimenez, Patricia; Song, Hairong; Vita, Marina; Cedazo-Minguez, Angel; Hassan, Moustapha


    Roscovitine is a cyclin-dependent kinase (Cdk) and signal-regulated kinase (Erk1/2) inhibitor that has been shown to be effective against several cancer types including brain tumors. We have shown previously that roscovitine crosses the blood brain barrier (BBB) and is rapidly eliminated from both plasma and brain in adult rats. However, age-dependent kinetics and its effects on the brain have not been reported. In the present study, we investigated the pharmacokinetics of roscovitine in adult and in 14 days old rats after the administration of a single dose of 25 mg/kg. Moreover, we studied the effect of the drug on Cdk5 and Erk1/2 activities in three brain regions, hippocampus, frontal cortex and cerebellum. The pharmacokinetics of roscovitine followed a two-compartment model in both plasma and brain in both adult and young rats. The terminal elimination half-life was 7 h in brain as well as in plasma in rat pups compared to Roscovitine induced a significant Cdk5 inhibition and significant Erk1/2 activation in all studied pups brain regions at 2 h. This is the first study describing age-dependent pharmacokinetics of roscovitine and showing the high brain exposure of infant rats to the drug. Thus, roscovitine may be a promising candidate for the treatment of brain tumors in children.

  1. A novel recombinant slow-release TNF α-derived peptide effectively inhibits tumor growth and angiogensis.

    Ma, Yi; Zhao, Shaojun; Shen, Shutao; Fang, Shixiong; Ye, Zulu; Shi, Zhi; Hong, An


    RMP16, a recombinant TNF α-derived polypeptide comprising a specific human serum albumin (HSA)-binding 7-mer peptide identified by phage display screening (WQRPSSW), a cleavage peptide for Factor Xa (IEGR), and a 20-amino acid bioactive peptide P16 (TNF α segment including amino acid residues 75-94), was prepared by gene-engineering technology. RMP16 showed prolonged half-life, 13.11 hours in mice (half-lives of P16 and TNF α are 5.77 and 29.0 minutes, respectively), and obviously higher receptor selectivity for TNFRI than TNF α. RMP16 had significant inhibition effects for multiple tumor cells, especially prostate cancer Du145 cells, and human vascular endothelial cells but not for human mammary non-tumorigenic epithelial cells. RMP16 can more effectively induce apoptosis and inhibit proliferation for DU145 cells than P16 and TNF α via the caspase-dependent apoptosis pathway and G0/G1 cell cycle arrest. In nude mice with transplanted tumor of DU145 cells, RMP16 significantly induced apoptosis and necrosis of tumor tissues but causing less side effects, and tumor inhibitory rate reached nearly 80%, furthermore, RMP16 can potently inhibit tumor angiogenesis and neovascularization. These findings suggest that RMP16 may represent a promising long-lasting antitumor therapeutic peptide with less TNF α-induced toxicity.

  2. Effect

    Amin Abdou Seleem; Fakhr El-Din M. Lashein


    Verapamil is a calcium channel blocker that belongs to the phenylalkylamine group. It has been clinically used for various diseases such as combating hypertension, ischemic heart diseases, supraventricular antiarrhythmic and tycolysis. The study was conducted to investigate the effect of verapamil on selected pro- and apoptotic factors during prenatal retinal differentiation of mice at E14 and E17 of gestation. The pregnant females were classified into two groups, the first is the control and...

  3. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on signal transduction pathway-related protein expression in liver and cerebrum of rhesus monkey

    Ohta, Mari; Akema, Satoshi; Tsuzuki, Masami; Kubota, Shunichiro [Tokyo Univ. (Japan); Korenaga, Tatsumi; Fukusato, Toshio [Teikyo Univ. of School of Medicine, Tokyo (Japan); Asaoka, Kazuo [Kyoto Univ. (Japan); Murata, Nobuo [Teikyo Univ. of School of Medicine, Kawasaki (Japan); Nomizu, Motoyoshi [Hokkaido Univ., Sapporo (Japan); Arima, Akihiro [Shin Nippon Biomedical Laboratories, Ltd., Kagoshima (Japan)


    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to produce a wide range of toxic and biochemical effects in experimental animals, including immunological dysfunctions, chloracne, tetragenecity and carcinogenesis. Recently, the potential impact of dioxins on neurological disorders with particular focus on attention deficit hyperactivity disorder (ADHD) are concerned. Although a lot of information is available from studies in rodents, not much is known of the low dose effects of TCDD in non-human primates. In higher animals, dioxins are metabolized slowly, as evidenced by the estimated TCDD half-life of 5.8 to 14.1 years. Therefore, it is necessary to investigate the long-term effects of TCDD on human health. Considering the pronounced species differences observed in some studies of TCDD, the studies using primates are needed for assessment of TCDD exposure on human health. We have been studying the metabolism and the effects of single administration of TCDD on pregnant monkey (F0) and F1 rhesus monkey. The focus of the present study is to study the effects of TCDD on signal transduction pathway-related protein levels in various organs, especially in liver and brain of F0 monkeys.

  4. Pharmacodynamic and pharmacokinetic effects of flumazenil and theophylline application in rats acutely intoxicated by diazepam

    Šegrt Zoran


    Full Text Available Background/Aim. The majority of symptoms and signs of acute diazepam poisoning are the consequence of its sedative effect on the CNS affecting selectively polisynaptic routes by stimulating inhibitory action of GABA. The aim of the present study was to examine the effects of combined application of theophylline and flumazenil on sedation and impaired motor function activity in acute diazepam poisoning in rats. Methods. Male Wistar rats were divided in four main groups and treated as follows: group I - with increasing doses of diazepam in order to produce the highest level of sedation and motor activity impairment; group II - diazepam + different doses of flumazenil; group III - diazepam + different doses of theophylline; group IV - diazepam + combined application of theophylline and flumazenil. Concentrations of diazepam and its metabolites were measured with LC-MS. The experiment was performed on a commercial apparatus for spontaneous motor-activity registration (LKBFarad, Sweden. Assessment of diazepam- induced neurotoxic effects and effects after theophylline and flumazenil application was performed with rotarod test on a commercial apparatus (Automatic treadmill for rats, Ugo Basile, Italy. Results. Diazepam in doses of 10 mg/kg and 15 mg/kg produced long-time and reproducible pharmacodynamic effects. Single application of flumazenil or theophylline antagonized effects of diazepam, but not completely. Combined application of flumazenile and theophylline resulted in best effects on diazepaminduced impairment of motoric activity and sedation. As a result of theopylline application there was better elimination of diazepam and its metabolites. Conclusion. Combined application of flumazenil and theophylline resulted in the best antidotal effects in the treatment of diazepam poisoned rats. These effects are a result of different mechanisms of their action, longer half-life of theophylline in relation to that of flumezenil and presumably the

  5. Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

    Magd A. Kotb


    Full Text Available Ursodeoxycholic acid (UDCA is a steroid bile acid approved for primary biliary cirrhosis (PBC. UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively. “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day and toxic dose (28 mg/kg/day, and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

  6. Effect of food and various antacids on the absorption of tenoxicam.

    Day, R O; Lam, S; Paull, P; Wade, D


    1 Twelve healthy volunteers received a single oral dose of tenoxicam 20 mg on six occasions separated by 3 weeks. 2 The six occasions were: fasted overnight; postprandial; fasting and 15 ml aluminium hydroxide gel; postprandial and 15 ml aluminium hydroxide gel; fasting and 15 ml aluminium and magnesium hydroxide gel; postprandial and 15 ml aluminium and magnesium hydroxide gel. 3 Twenty plasma samples were collected over 15 days following dosing with tenoxicam. 4 The following kinetic parameters for plasma tenoxicam were compared: peak concentrations, time taken to reach peak concentrations, area under the plasma concentration-time curve (AUC) and half-life of elimination. 5 Food lengthened the time taken to reach peak tenoxicam concentrations (5.82 +/- 4.6 vs 1.84 +/- 1.0 h in the fasting state; P less than 0.02) and marginally reduced the peak concentrations achieved. AUC was not affected by any of the different regimens. 6 These effects of food on tenoxicam bioavailability are unlikely to be of clinical significance during chronic dosing with the drug. PMID:3499163

  7. Effects of Green Tea Extracts on the Pharmacokinetics of Quetiapine in Rats

    Essam Ezzeldin


    Full Text Available Quetiapine is an atypical antipsychotic, used clinically in the treatment of schizophrenia, acute mania in bipolar disorders, and bipolar depression in adults. In this study, the effect of green tea extracts (GTE on the pharmacokinetics of quetiapine (substrate of CYP3A4 was investigated in rats. Male Wistar albino rats received GTE (175 mg/kg or saline (control by oral gavage for 7 days before a single intragastric administration of 25 mg/kg quetiapine. Plasma concentrations of quetiapine were measured up to 12 h after its administration by a validated ultraperformance liquid chromatography-tandem mass spectroscopy. Pretreatment with GTE produced significant reductions in the maximum plasma concentration and area under the curve of quetiapine by 45% and 35%, respectively, compared to quetiapine alone. However, GTE did not produce significant change in elimination half-life and oral clearance of quetiapine. This study concluded that GTE may decrease the bioavailability of quetiapine when coadministered.

  8. Effect of copper on the degradation of pesticides cypermethrin and cyhalothrin


    The influence of coexisting copper (Cu) ion on the degradation of pesticides pyrethroid cypermethrin and cyhalothrin in soil and photodegradation in water system were studied. Serial concentrations of the pesticides with the addition of copper ion were spiked in the soil and incubated for a regular period of time, the analysis of the extracts from the soil was carried out using gas chromatography(GC). The photodegradation of pyrethroids in water system was conducted under UV irradiation. The effect of Cu2+ on the pesticides degradation was measured with half life (t0.5) of degradation. It was found that a negative correlation between the degradation of the pyrethroid pesticides in soil and Cu addition was observed. But Cu2+ could accelerate photodegradation of the pyrethroids in water. The t0.5 for cyhalothrin extended from 6.7 to 6.8 d while for cypermethrin extended from 8.1 to 10.9 d with the presence of copper ion in soil. As for photodegradation, t0.5 for cyhalothrin reduced from 173.3 to 115.5 min and for cypermethrin from 115.5 to 99.0 min. The results suggested that copper influenced the degradation of the pesticides in soil by affecting the activity of microorganisms. However,it had catalyst tendency for photodegradation in water system. The difference for the degradation efficiency of pyrethroid isomers in soil was also observed. Copper could obviously accelerate the degradation of some special isomers.

  9. Effects of mexiletine, a CYP1A2 inhibitor, on tizanidine pharmacokinetics and pharmacodynamics.

    Momo, Kenji; Homma, Masato; Osaka, Yoshiko; Inomata, Shin-ichi; Tanaka, Makoto; Kohda, Yukinao


    The aim of this study was to determine whether mexiletine, a CYP1A2 inhibitor, altered the pharmacokinetics and pharmacodynamics of tizanidine. The pharmacokinetics of tizanidine were examined in an open-label study in 12 healthy participants after a single dose of tizanidine (2 mg) with and without mexiletine coadministration (50 mg, 3 times as a pretreatment for a day and 2 times on the study day). Compared with tizanidine alone, mexiletine coadministration increased the peak plasma concentration (1.8 +/- 0.8 vs 5.3 +/- 1.8 ng/mL), area under the curve (4.5 +/- 2.2 vs 15.4 +/- 6.5 ng x h/mL), and the half-life (1.3 +/- 0.2 vs 1.8 +/- 0.7 h) of tizanidine, respectively (P < .05). Reduction in systolic blood pressure (-10 +/- 8 vs -24 +/- 7 mm Hg) and diastolic blood pressure (-10 +/- 7 vs -18 +/- 8 mm Hg) after tizanidine administration was also significantly enhanced by coadministration of mexiletine (P < .01). Of the 15 patients treated with tizanidine and mexiletine, 4 suffered tizanidine-induced adverse effects such as drowsiness and dry mouth in the retrospective survey. Present results suggested that coadministration of mexiletine increased blood tizanidine concentrations and enhanced tizanidine pharmacodynamics in terms of reduction in blood pressure and adverse symptoms.

  10. New in vitro model to study the effect of human simulated antibiotic concentrations on bacterial biofilms.

    Haagensen, Janus A J; Verotta, Davide; Huang, Liusheng; Spormann, Alfred; Yang, Katherine


    A new in vitro pharmacokinetic/pharmacodynamic simulator for bacterial biofilms utilizing flow cell technology and confocal laser scanning microscopy is described. The device has the ability to simulate the changing antibiotic concentrations in humans associated with intravenous dosing on bacterial biofilms grown under continuous culture conditions. The free drug concentrations of a single 2-g meropenem intravenous bolus dose and first-order elimination utilizing a half-life of 0.895 h (elimination rate constant, 0.776 h(-1)) were simulated. The antibacterial activity of meropenem against biofilms of Pseudomonas aeruginosa PAO1 and three clinical strains isolated from patients with cystic fibrosis was investigated. Additionally, the effect of meropenem on PAO1 biofilms cultured for 24 h versus that on biofilms cultured for 72 h was examined. Using confocal laser scanning microscopy, rapid biofilm killing was observed in the first hour of the dosing interval for all biofilms. However, for PAO1 biofilms cultured for 72 h, only bacterial subpopulations at the periphery of the biofilm were affected, with subpopulations at the substratum remaining viable, even at the conclusion of the dosing interval. The described model is a novel method to investigate antimicrobial killing of bacterial biofilms using human simulated concentrations.

  11. Effects of green tea extract and (-)-epigallocatechin-3-gallate on pharmacokinetics of nadolol in rats.

    Misaka, S; Miyazaki, N; Fukushima, T; Yamada, S; Kimura, J


    Green tea catechins have been shown to affect the activities of drug transporters in vitro, including P-glycoprotein and organic anion transporting polypeptides. However, it remains unclear whether catechins influence the in vivo disposition of substrate drugs for these transporters. In the present study, we investigated effects of green tea extract (GTE) and (-)-epigallocatechin-3-gallate (EGCG) on pharmacokinetics of a non-selective hydrophilic β-blocker nadolol, which is reported to be a substrate for several drug transporters and is not metabolized by cytochrome P450 enzymes. Male Sprague-Dawley rats received GTE (400 mg/kg), EGCG (150 mg/kg) or saline (control) by oral gavage, 30 min before a single intragastric administration of 10 mg/kg nadolol. Plasma and urinary concentrations of nadolol were determined using high performance liquid chromatography. Pharmacokinetic parameters were estimated by a noncompartmental analysis. Pretreatment with GTE resulted in marked reductions in the maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) of nadolol by 85% and 74%, respectively, as compared with control. In addition, EGCG alone significantly reduced Cmax and AUC of nadolol. Amounts of nadolol excreted into the urine were decreased by pretreatments with GTE and EGCG, while the terminal half-life of nadolol was not different among groups. These results suggest that the coadministration with green tea catechins, particularly EGCG, causes a significant alteration in the pharmacokinetics of nadolol, possibly through the inhibition of its intestinal absorption mediated by uptake transporters.

  12. Metabolic peculiarity of 134Cs and its radioimmunotoxicological effect on central and peripheral immune cells

    朱寿彭; 夏芬


    A fitted equation with least square method to describe the retention of 134Cs in whole body is obtained by a whole body counter.That is R(t)=18.04exp(-9.3175t)+ 45.13exp(-0.0423t),where R(t) is in %,and t in d.The equationn consists of two half-life components,the fast component is T1/2=0.07d,and the slow is T1/2=16.14d,Study on the localization of 134Cs at cellular level was carried out by freezing microautoradiography.The results indicate of 134Cs at cellular level was carried out by freezing microautoradiography.The results indicate that 134Cs was chiefly in ionizing form accumulated in red as well as white blood cells.In bone marrow cells 134Cs predominantly deposited in young cells and less in mature cells.Distribution of 134Cs penetrated quickly into the tissue cells.The observation of investigating radioimmunotoxicological effect induced by 134Cs shows that the inhibition of thymocytes is higher than bone marrow cells,the spleen T lynmphocytes are more sensitive to 134Cs than B lymphocytes and lymphocytes of peripheral immune cells are more sensitive to radiation than central immune cells.

  13. Effects of interlinker sequences on the biological properties of bispecific single-chain antibodies

    FANG Min; JIANG Xin; YANG Zhi; YIN Changcheng; LI Hua; ZHAO Rui; ZHANG Zhong; LIN Qing; HUANG Hualiang


    Single-chain bispecific antibody (scBsAb) is one of the promising genetic engineering antibody formats for clinical application. But the effects of interlinker sequences on the biological properties of bispecific single-chain antibodies have not been studied in detail. Three interlinker sequences were designed and synthesized, and denominated as Fc, HSA, 205C′, respectively. Universal vectors with these different interlinker sequences for scBsAb expression in E. coli were constructed. A model scBsAb based on a reshaped single-chain antibody (scFv) against human CD3 and a scFv directed against human ovarian carcinoma were generated and expressed in E. coli. The results of SDS-PAGE and Western blot showed that the different interlinker sequences did not affect the expression levelof scBsAb. However, as demonstrated by ELISA and pharmacokinetics studies performed in mice, scBsAbs with different interlinker sequences had difference in the antigen-binding activities and terminal half-life time (T1/2β) in vivo, the interlinker HSA could remarkably prolong the retention time of scBsAb in blood. These results indicated that the peptide sequence of interlinker could affect important biological properties of scBsAb, such as antigen-binding properties and stability in vivo. So, selection of an appropriate interlinker sequence is very important for scBsAb construction. Optimal interlinker can bring scBsAb biologicalproperties more suitable for clinical application.

  14. Laboratory studies on the effect of ozonation on THM formation in swimming pool water

    Hansen, Kamilla Marie Speht; Spiliotopoulou, Aikaterini; Cheema, Waqas Akram


    Water samples from indoor swimming pool were ozonated at different pH values to evaluate the effect of pH on decomposition of ozone in swimming pool water. Furthermore, drinking and pool water were repeatedly ozonated followed by chlorination to evaluate THM formation. Decomposition of ozone...... was not affected by pH in the range relevant to swimming pools (pH 6.8 – 7.8) and a half-life time at 10-12 min was obtained. Repeating the ozonation, the decomposition of ozone increased at the second dose of ozone added (t½,2=8 min) and then decreased again at the third and fourth dose of ozone (t½,3=17 min; t...... chlorine for drinking water as lower TTHM formation occurred than in non-ozonated samples. For pool water, a higher TTHM formation was observed in ozonated than non-ozonated pool water. Thus, it was observed that ozone reacts markedly different in swimming pool water from the known pattern in drinking...

  15. Effect of nitrogen supplementation on aerobic degradation of linear alkylbenzene sulfonate by consortia of bacteria

    Kehinde I. Temitope Eniola


    Full Text Available Untreated detergent bearing wastes discharged into the environment are sources of linear alkylbenzene sulfonate (LAS. Detergent wastes usually do not contain nitrogen or contain very low amounts. Biostimulation by introducing limiting nutrient element can be useful in biotreatment of such waste. The effect of inorganic and organic nitrogen supplements on aerobic degradation of LAS by LAS-utilizing bacteria was examined. Phosphate-buffered LAS mineral media were prepared and supplemented with different nitrogen sources: NPK fertilizer (inorganic and urea fertilizer (organic. Individual and various consortia of pure cultures of Alcaligenes odorans, Citrobacter diversus, Micrococcus luteus and Pseudomonas putida, previously isolated from a detergent effluent polluted stream, were used. Biodegradation of LAS was monitored in terms of half-life (t½ of the surfactant. The rates of biodegradation by the consortia can be ranked as: 4-membered (t½=8-12 days >3-membered (t½=8-13 days >2-membered consortia (t½=10-15 days >individuals (t½=9-16 days. The inorganic nitrogen source enhanced utilization of the surfactant, while organic nitrogen supplementation generally slowed degradation of the surfactant. In undertaking biotreatment of detergent bearing effluent, inorganic nitrogen should be used as biostimulant.

  16. The effect of moderate urine alkalinisation on low dose diethylcarbamazine therapy in patients with onchocerciasis.

    Awadzi, K; Adjepon-Yamoah, K K; Edwards, G; Orme, M L; Breckenridge, A M; Gilles, H M


    Twenty-one patients with moderate to heavy infections with O. volvulus were treated with 25 mg of diethylcarbamazine (DEC) citrate twice daily for 10 days. In 11 patients the urine was made alkaline with sodium bicarbonate, 2 g, administered 6 hourly for three doses daily beginning 1 day before DEC was started and continued throughout the DEC therapy. Ten patients served as controls. The mean pre-dose plasma DEC concentration during treatment and the mean plasma DEC half-life were significantly higher in bicarbonate treated patients as compared to controls. Total urinary excretion of DEC was significantly less in the bicarbonate treated group than in controls. Mean overall total reaction was higher in bicarbonate-treated patients but the difference was not significant. The bicarbonate-treated group achieved a significantly greater reduction in skin microfilarial counts than the control group as assessed 1 week after completion of therapy, but there was little difference at 1 month. Microfilarial killing was associated with microfilarial mobilisation, alteration in peripheral leucocytes and elevation in serum aminotransferases in both groups. There was no effect of DEC on the number of adult worms recovered in nodules removed at the end of the therapy. This study indicates that moderate urinary alkalinisation alters the kinetics of DEC and the therapeutic response. However the severity of clinical reaction coupled with the inadequate level of microfilarial killing achieved make it unlikely that manipulation of urinary pH will be of practical value in onchocerciasis chemotherapy.

  17. Effect of Different Nucleating Agents on the Crystallization of Ziegler-Natta Isotactic Polypropylene

    Felipe Avalos-Belmontes


    Full Text Available Ziegler-Natta isotactic polypropylene (iPP was melt mixed with four different nucleating agents (carbon nanotubes (CNT, carbon nanofibers (CNF, lithium benzoate (LiBe, and a sorbitol derivative (Millad in order to study their effect on the crystallization of iPP. It was found that the four different nucleating agents promote the alpha crystalline form. At 0.01 wt%, the carbon nanoparticles produced the higher crystallization temperature “Tc” (~119°C, whereas, at 0.10 wt%, LiBe and Millad produced a markedly higher Tc (~125°C. Tc of pure iPP was 111°C. With 0.1 wt% nucleating agent, at 120°C, the crystallization half-life time of PP, when using LiBe or Millad, was 15 times faster than for pure PP, whereas, when using carbon nanoparticles, it was 20–25 times faster. At 135°C, with 0.01 wt% nucleating agent, the isothermal crystallization process of iPP was completed after 25 min, as well as with Millad. With LiBe, it was completed after just 15 min and, with any of the carbon nanoparticles, it was practically over after only a couple of minutes.

  18. Toxicogenomic evaluation of long-term hepatic effects of TCDD in immature, ovariectomized C57BL/6 mice.

    Kopec, Anna K; Boverhof, Darrell R; Nault, Rance; Harkema, Jack R; Tashiro, Colleen; Potter, Dave; Sharratt, Bonnie; Chittim, Brock; Zacharewski, Timothy R


    Acute exposure to hepatotoxic doses of 2,3,7,8-tetrachloro- dibenzo-p-dioxin (TCDD) in mice is characterized by differential gene expression that can be phenotypically anchored to elevated levels of serum alanine aminotransferase, increased relative liver weights, hepatic steatosis, inflammation, and hepatocellular necrosis. Unlike most studies that focus on acute exposure effects, this study evaluated the long-term effects of a single oral gavage of 30 μg/kg TCDD at 1, 4, 12, 24, 36, and 72 weeks postdose in ovariectomized C57BL/6 mice. Hepatic TCDD levels were almost completely eliminated by 24 weeks with a calculated half-life of 12 days. Hepatic gene expression analysis identified 395 unique differentially expressed genes between 1 and 12 weeks that decreased to ≤ 8 by 72 weeks, consistent with the minimal hepatic TCDD levels. Hepatic vacuolization, characteristic of short-term exposure, subsided by 4 weeks. Similarly, TCDD-elicited hepatic necrosis and inflammation dissipated by 1 week. Collectively, these results suggest that TCDD-elicited histologic and gene expression responses can be correlated to elevated hepatic TCDD levels, which, once eliminated, elicit minimal hepatic gene expression and histologic alterations.

  19. The effect of a heparin-based coacervate of fibroblast growth factor-2 on scarring in the infarcted myocardium.

    Chu, Hunghao; Chen, Chien-Wen; Huard, Johnny; Wang, Yadong


    Effective delivery of exogenous angiogenic growth factors can provide a new therapy for ischemic diseases. However, clinical translation of growth factor therapies faces multiples challenges; the most significant one is the short half-life of the naked protein. We use heparin and a nontoxic polycation to form an injectable coacervate that protects growth factors and preserves their bioactivities. Here we report the effectiveness of fibroblast growth factor-2 (FGF2) coacervate in reducing scar burden in a mouse myocardial infarction model. The coacervate provides spatial and temporal control of the release of heparin-binding proteins. Coacervate treated animals show lower level of inflammation, fibrosis and cardiomyocyte death in the infarcted myocardium. Histological evaluation indicates that FGF2 coacervate significantly increases the number of endothelial and mural cells and results in stable capillaries and arterioles to at least 6 weeks post injection. Echocardiographic assessment shows that FGF2 coacervate promotes cardiac contractibility and inhibits ventricular dilation, suggesting that the improvement at the tissue level leads to better cardiac functions. On the contrary, identical dosage of free FGF2 shows no statistical difference from saline or vehicle control in histological or functional assessment. Overall, injection of FGF2 coacervate ameliorated the ischemic injury caused by myocardial infarction. The promising data in rodent warrant further examination of the potential of clinical translation of this technology.

  20. Pharmacokinetics and cardiovascular effect of etoricoxib in the absence or presence of St. John's Wort in rats.

    Radwan, M A; Baky, N A A; Zaghloul, I; Aboul-Enein, H Y


    The effect of chronic administration of etoricoxib (EXB), in the absence or presence of St. John's Wort (SJW), on its pharmacokinetic parameters and blood pressure was investigated in rats.Rats were divided into 3 groups, each group received daily different oral treatment for 3 weeks. Rats' blood pressures were monitored initially, after 1 and 3 weeks of treatment, and after 1 week of discontinuing dosing of both drugs. EXB pharmacokinetic parameters in the absence or presence of SJW were calculated after 3 weeks.SJW was significantly affected EXB pharmacokinetic parameters. The steady state peak plasma concentration and terminal half-life were reduced by 32% and 91%, respectively, due to a > 3 fold increase in its apparent clearance which is a concentration and time dependent effect. EXB was significantly increased (P0.05) rats' blood pressure as compared to the control.Monitoring blood pressure of patients anticipated taking EXB for extended period should be advised. The co-administration of SJW with EXB should be avoided since SJW would greatly reduce EXB concentrations by inducing its metabolism.

  1. [Effectiveness of intercostal nerve block with ropivacaine in analgesia of patients undergoing emergency open cholecystectomy under general anesthesia].

    Vizcarra-Román, M A; Bahena-Aponte, J A; Cruz-Jarquín, A; Vázquez-García, Ja C; Cárdenas-Lailson, L E


    Postoperative pain after open cholecystectomy is associated with reduced respiratory function, longer recovery period before deambulation and oral food intake, and prolonged hospital stay. Intercostal nerve block provides satisfactory analgesia and ropivacaine is the most widely used local anesthetic agent in intercostal nerve block due to its excellent effectiveness, lower cardiovascular toxicity, and longer half-life. To evaluate intercostal nerve block effectiveness with ropivacaine in patients undergoing emergency open cholecystectomy under general anesthesia compared with conventional management. A controlled clinical trial was carried out on 50 patients undergoing open cholecystectomy, 25 patients without intercostal nerve block versus 25 patients with intercostal nerve block using ropivacaine at 0.5% combined with epinephrine. Intraoperative minimum alveolar concentration and inhalation anesthetic use were evaluated. Tramadol as rescue analgesic agent and pain were evaluated during immediate postoperative period by means of the Visual Analog Scale at 8, 16, and 24 hours. Mean inhalation anesthetic use was lower in the intercostal nerve block group with 13% vs 37% in the group without intercostal nerve block (p= 0.01). Rescue tramadol requirement was lower in the intercostal nerve block group than in the group without intercostal nerve block at 8 hours (8% vs 67%), 16 hours (0% vs 83%), and 24 hours (12% vs 79%) (pIntercostal nerve block reduces intraoperative inhalation anesthetic use, immediate postoperative pain, and tramadol intake as rescue analgesic agent in patients undergoing open cholecystectomy.

  2. Kresoxim methyl dissipation kinetics and its residue effect on soil extra-cellular and intra-cellular enzymatic activity in four different soils of India.

    Sabale, Rupali P; Shabeer T P, Ahammed; Utture, Sagar C; Banerjee, Kaushik; Oulkar, Dasharath P; Adsule, Pandurang G; Deshmukh, Madhukar B


    The rate of degradation of kresoxim methyl and its effect on soil extra-cellular (acid phosphatase, alkaline phosphatase and β-glucosidase) and intra-cellular (dehydrogenase) enzymes were explored in four different soils of India. In all the tested soils, the degradation rate was faster at the beginning, which slowed down with time indicating a non-linear pattern of degradation. Rate of degradation in black soil was fastest followed by saline, brown and red soils, respectively and followed 1st or 1st + 1st order kinetics with half-life ranging between 1-6 days for natural soil and 1-19 days for sterile soils. The rate of degradation in natural against sterilized soils suggests that microbial degradation might be the major pathway of residue dissipation. Although small changes in enzyme activities were observed, kresoxim methyl did not have any significant deleterious effect on the enzymatic activity of the various test soils in long run. Simple correlation studies between degradation percentage and individual enzyme activities did not establish any significant relationships. The pattern and change of enzyme activity was primarily due to the effect of the incubation period rather than the effect of kresoxim methyl itself.

  3. Prandial effect on the systemic exposure of amisulpride.

    Jang, Yoo-Jung; Jeong, Tae Cheon; Noh, Keumhan; Baek, In-Whan; Kwon, Kwang-il; Kim, Eunyoung; Yoon, Young-Ran; Kang, Wonku


    A substituted benzamide, amisulpride is an atypical antipsychotic and a specific antagonist for dopamine D2 and D3 receptors. The prandial effect on amisulpride absorption remains unclear, therefore, this study was designed to investigate the effect of food on the systemic exposure to amisulpride in healthy volunteers. The study was a randomized, two-way crossed trial in which a single oral dose of amisulpride was administered on two occasions, with 7-days washout period between each drug administration. The volunteers were randomly divided into two groups and received amisulpride (50 mg) with Korean traditional food or under fasting state. Blood was serially taken, and the plasma amisulpride concentrations were measured by LC/MS/MS. At fasting state, amisulpride reached the first peak (37.1 ± 13.3 ng/ml) at ~2.3 h, and decreased down to 19.4 ± 4.3 ng/ml until 3.5 h, and then again went up to the second peak (25.3 ± 5.8 ng/ml) at 5 h followed by a slow decay with 10.6 h of half-life. In contrast, no double peaks were shown when the drug was given with meal. The maximum concentration of amisulpride (56.0 ± 12.7 ng/ml) was increased by a 1.5-fold compared with that under fasting (p > 0.05), and the time to peak shortened a little (1.7 ± 0.6 h).

  4. Autophagy enhancement contributes to the synergistic effect of vitamin D in temozolomide-based glioblastoma chemotherapy



    Temozolomide (TMZ), an alkylating agent, is recommended as the initial treatment for high-grade glioblastoma. TMZ is widely used, but its short half-life and the frequency of tumor resistance limit its therapeutic efficacy. In the present study, the anticancer effect of vitamin D (VD) combined with TMZ upon glioblastoma was determined, and the underlying mechanism of this effect was identified. Through cell viability, clonogenic and wound healing assays, the current study demonstrated that treatment of a C6 glioblastoma cell line with TMZ and VD resulted in significantly increased in vitro antitumor effects compared with either VD or TMZ alone. Autophagy, hypothesized to be the dominant mechanism underlying TMZ-based tumor cell death, was maximally activated in TMZ and VD co-treated C6 cells. This was demonstrated by ultrastructural observations of autophagosomes, increased size and number of microtubule-associated protein 1 light chain 3 (LC3) puncta and increased conversion of LC3-I to LC3-II. However, the extent of apoptosis was not significantly different between cells treated with TMZ and VD and those treated with TMZ alone. Addition of the autophagy inhibitor 3-methyladenine markedly inhibited the anticancer effect of TMZ and VD treatment, indicating that the chemosensitizing effect of VD in TMZ-based glioblastoma therapy is generated through enhancement of cytotoxic autophagy. TMZ and VD co-treatment also significantly inhibited tumor progression and prolonged survival duration in rat glioblastoma orthotopic xenograft models when compared with TMZ treatment alone. These in vivo results are concordant with the aforementioned in vitro results, together revealing that the combined use of TMZ and VD exerts synergistic antitumor effects on rat models of glioblastoma and may represent an effective therapeutic strategy. PMID:27313664

  5. Dose-rate effects of ethylene oxide exposure on developmental toxicity.

    Weller, E; Long, N; Smith, A; Williams, P; Ravi, S; Gill, J; Henessey, R; Skornik, W; Brain, J; Kimmel, C; Kimmel, G; Holmes, L; Ryan, L


    In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.

  6. Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure

    van Gilst Wiek H


    Full Text Available Abstract Background Progressive remodeling after myocardial infarction (MI is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4, an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4 inhibitor vildagliptin will increase levels of GLP-1 and may exert protective effects on cardiac function after MI. Methods Sprague-Dawley rats were either subjected to coronary ligation to induce MI and left ventricular (LV remodeling, or sham operation. Parts of the rats with an MI were pre-treated for 2 days with the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15 mg/kg/day. The remainder of the rats was, three weeks after coronary artery ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI-Vildagliptin Late, MI-VL or control (MI. At 12 weeks, echocardiography and invasive hemodynamics were measured and molecular analysis and immunohistochemistry were performed. Results Vildagliptin inhibited the DPP-4 enzymatic activity by almost 70% and increased active GLP-1 levels by about 3-fold in plasma in both treated groups (p Conclusion Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model.

  7. Effects of the pyrethroid insecticide, cypermethrin, on a freshwater community studied under field conditions. I. Direct and indirect effects on abundance measures of organisms at different trophic levels

    Friberg-Jensen, Ursula; Wendt-Rasch, Lina; Woin, Per; Christoffersen, Kirsten


    The effects of the pyrethroid insecticide cypermethrin on a natural freshwater community were studied in small in situ enclosures over an 11-day period. The experiment was conducted in a eutrophic lake using a regression design that included three untreated controls and a gradient of six unreplicated cypermethrin concentrations, ranging from 0.01 to 6.1 {mu}g/l. This paper is the first in a series of two, and describes the fate of cypermethrin and its effects on the abundance of crustaceans, rotifers, protozoans (cilliates and heterotrophic nanoflagellates (HNF)) and bacteria and the biomass of periphytic and planktonic algae. The concentration of cypermethrin decreased quickly during the experiment, with a half-life of 48 h for the total and 25 h for the dissolved fractions of cypermethrin, respectively. Cypermethrin proved to be acutely toxic to crustaceans in enclosures receiving nominal cypermethrin concentrations of {>=}0.13 {mu}g/l. No Effect Concentration (NEC) and median Effect Concentration (EC{sub 50}) for the total crustacean community and cladoceran and copepod subgroups ranged between 0.02-0.07 and 0.04-0.17 {mu}g/l, respectively, with copepods being less sensitive than cladocerans. The abundance of rotifers, protozoans and bacteria and the chlorophyll-a concentration of planktonic and periphytic algae was significantly related to the concentration of cypermethrin. All groups proliferated within 2-7 days after the cypermethrin application in those enclosures where the abundance of crustaceans was seriously affected by cypermethrin (i.e. {>=}0.13 {mu}g/l). We hypothesise that the proliferation of rotifers, protozoans, bacteria and algae was due to a reduced grazer control from crustaceans and thereby mediated indirectly by cypermethrin. The results of this experiment provide knowledge on how an entire microplankton community may respond to pyrethroids in nature, and the indirect effects observed on the community clearly demonstrates the necessity of

  8. Long-range effects and functional consequences of stabilizing mutations in the ankyrin repeat domain of IκBα.

    Cervantes, Carla F; Handley, Lindsey D; Sue, Shih-Che; Dyson, H Jane; Komives, Elizabeth A


    Protein domains containing three or more ankyrin repeats (ARs) are ubiquitous in all phyla. Sequence alignments previously identified certain conserved positions, which have been shown to stabilize AR domains and promote their folding. Consensus mutations [Y254L/T257A (YLTA) and C186P/A220P (CPAP)] stabilize the naturally occuring AR domain of human IκBα to denaturation; however, only the YLTA mutations stabilize the protein to proteasomal degradation. We present results from NMR experiments designed to probe the roles of these consensus mutations in IκBα. According to residual dipolar coupling analysis, the gross structures of the AR domains of both mutants appear to be similar to the wild type (WT). Comparison of chemical shifts of mutant and WT proteins reveals that the YLTA and CPAP consensus mutations cause unexpected long-range effects throughout the AR domains. Backbone dynamics experiments reveal that the YLTA mutations in the sixth AR order the C-terminal PEST sequence on the picosecond-to-nanosecond timescale, compared to either the WT or the CPAP mutant IκBαs. This property is likely the mechanism by which the half-life of YLTA IκBα is extended in vivo.

  9. Effects on soil organic matter mineralization and microbiological properties of applying compost to burned and unburned soils.

    Turrión, M B; Lafuente, F; Mulas, R; López, O; Ruipérez, C; Pando, V


    This study was undertaken in the context of a project of reclamation of a burned forest area applying municipal waste compost (MWC) and it consisted of an incubation experience carried out under laboratory conditions. The objectives of this research were to asses the effect of three doses of MWC added to burned and unburned calcareous soils on a) SOM mineralization and b) soil microbiological parameters. The laboratory incubation experience was carried out with three compost doses (1, 2 and 4% w/w) on a burned soil and another unburned one from an adjacent plot, besides the corresponding control samples. The mineralization kinetics of the organic matter was studied for 92 days. The kinetics data were adjusted to a double exponential model, showing two C pools of different degrees of resistance to mineralization and concentration, with half-life times of 1.9-4.9 and 34-76 days, respectively. In the unburned soil, the initial potential mineralization rate of the labile and stable C pools showed an opposed behavior, increased and decreased with the MWC dose, respectively. However in the burned soil no significant tendencies were observed. Although applying compost tended to increase the size of more labile pool with respect to total mineralizable C, however most of the soil or compost OM did not result mineralizable in the short and medium term. The compost amendment did not increase soil microbial activity. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Inhibition of retinoblastoma mRNA degradation through Poly (A involved in the neuroprotective effect of berberine against cerebral ischemia.

    Yu-Shuang Chai

    Full Text Available Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb from degradation through its function on the poly(A tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1 mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine.

  11. Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses.

    Knych, H K; Arthur, R M; McKemie, D S; Chapman, N


    Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug concentrations reached the recommended regulatory threshold. Sixteen exercised adult horses received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up to 72 h postadministration and analyzed using LC-MS. Blood samples were collected from 8 horses for determination of TxB(2) and PGE(2) concentrations prior to and up to 96 h postflunixin administration. Mean systemic clearance, steady-state volume of distribution and terminal elimination half-life was 0.767 ± 0.098 mL/min/kg, 0.137 ± 0.12 L/kg, and 4.8 ± 1.59 h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24 h postadministration. TxB(2) suppression was significant for up to 24 h postadministration.

  12. Residues of azoxystrobin, fenhexamid and pyrimethanil in strawberry following field treatments and the effect of domestic washing.

    Angioni, A; Schirra, M; Garau, V L; Melis, M; Tuberoso, C I G; Cabras, P


    Residues of the pesticides azoxystrobin, fenhexamid and pyrimethanil were determined in strawberry after field treatment. The effect of 'home' washing with tap water and a commercially available vegetable detergent on residue levels was also studied. After treatment, azoxystrobin and pyrimethanil residues on strawberry were on average 0.55 and 2.98 mg kg(-1), respectively, values below the maximum residue level (MRL) fixed by the European Union (2.0 and 5 mg kg(-1), respectively), while fenhexamid residues were on average 2.99 mg kg(-1), which is very close to the MRL of 3.0 mg kg(-1), but some samples were over the MRL. Thereafter, all residues declined, with a half-life of about 8 days (azoxystrobin and fenhexamid) and 4.8 days (pyrimethanil). Washing the fruit with tap water reduced the residues of azoxystrobin and fenhexamid but did not affect pyrimethanil residues. Finally, when fruits were washed with a commercial detergent, greater amounts were removed (about 45% of azoxystrobin and pyrimethanil and 60% of fenhexamid).

  13. Effects of Mitragynine and a Crude Alkaloid Extract Derived from Mitragyna speciosa Korth. on Permethrin Elimination in Rats

    Kachamas Srichana


    Full Text Available Detoxification and elimination of permethrin (PM are mediated by hydrolysis via carboxylesterase (CES. Mitragyna speciosa (kratom contains mitragynine (MG and other bioactive alkaloids. Since PM and MG have the same catalytic site and M. speciosa is usually abused by adding other ingredients such as pyrethroid insecticides, the effects of MG and an alkaloid extract (AE on the elimination of PM were investigated in rats. Rats were subjected to single and multiple pretreatment with MG and AE prior to receiving a single oral dose (460 mg/kg of PM. Plasma concentrations of trans-PM and its metabolite phenoxybenzylalcohol (PBAlc were measured. The elimination rate constant (kel and the elimination half-life (t1/2 el of PM were determined, as well as the metabolic ratio (PMR. A single and multiple oral pretreatment with MG and AE altered the plasma concentration-time courses of both trans-PM and PBAlc during 8–22 h, decreased the PMRs, delayed elimination of PM, but enhanced elimination of PBAlc. Results indicated that PM–MG or AE toxicokinetic interactions might have resulted from the MG and AE interfering with PM hydrolysis. The results obtained in rats suggest that in humans using kratom cocktails containing PM, there might be an increased risk of PM toxicity due to inhibition of PM metabolism and elimination.

  14. The effect of cyclodextrins on chemical and physical stability of glucagon and characterization of glucagon/gamma-CD inclusion complexes.

    Matilainen, Laura; Larsen, Kim Lambertsen; Wimmer, Reinhard; Keski-Rahkonen, Pekka; Auriola, Seppo; Järvinen, Tomi; Jarho, Pekka


    The purpose of the study was to evaluate the effect of cyclodextrin (CD) complexation on the chemical and physical stability of a polypeptide hormone glucagon and to study the interactions between glucagon and gamma-cyclodextrin molecules in inclusion complexes. The chemical stability of glucagon at pH 2.0 was studied with HPLC-UV and HPLC-MS/MS. The physical stability of glucagon at pH 2.5 was studied by measuring the turbidity (A(405 nm)) and viscosity (Ostwald capillary viscosimeter) of the samples. The structure of glucagon/gamma-CD complexes at pH 2.5 was studied with 2D-NMR. The presence of various CDs increased the chemical half-life of glucagon at pH 2.0 (37 degrees C, 0.01 M HCl, ionic strength 0.15) and prolonged the lag-time before aggregation at pH 2.5 (0.9% (w/v) NaCl in 3.2 mM HCl). The NMR studies showed that the side chains of all the aromatic amino acid residues (Phe6, Tyr10, Tyr13, Phe22, Trp25) and leucines (Leu14 and Leu26) of glucagon interacted with the cavities of the gamma-CD molecules. The present study shows that glucagon forms inclusion complexes with cyclodextrins in acidic solution, resulting in an improvement in its chemical and physical stability.

  15. Insights into the Effect of Nitric Oxide and its Metabolites Nitrite and Nitrate at Inhibiting Neointimal Hyperplasia

    Vavra, Ashley K.; Havelka, George E.; Martinez, Janet; Lee, Vanessa R.; Fu, Bo; Jiang, Qun; Keefer, Larry K.; Kibbe, Melina R.


    Objective Periadventitial delivery of the nitric oxide (NO) donor PROLI/NO following arterial injury effectively inhibits neointimal hyperplasia. Given the short half-life of NO release from PROLI/NO, our goal was to determine if inhibition of neointimal hyperplasia by PROLI/NO was due to NO, or its metabolites nitrite and nitrate. Methods and Results In vitro, the NO donor DETA/NO inhibited proliferation of rat aortic vascular smooth muscle cells (RASMC), but neither nitrite nor nitrate did. In vivo, following rat carotid artery balloon injury or injury plus the molar equivalents of PROLI/NO, nitrite, or nitrate (n=8–11/group), PROLI/NO was found to provide superior inhibition of neointimal hyperplasia (82% inhibition of intimal area, and 44% inhibition of medial area, phyperplasia following arterial injury than nitrite or nitrate. However, modest inhibition of neointimal hyperplasia was observed with nitrite and nitrate, likely secondary to anti-inflammatory actions. In conclusion, we have demonstrated that the efficacy of NO donors is primarily due to NO production and not its metabolites, nitrite and nitrate. PMID:21554972

  16. Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG₂₀₀₀ micelles.

    Cai, Lulu; Qiu, Neng; Xiang, Mingli; Tong, Rongsheng; Yan, Junfeng; He, Lin; Shi, Jianyou; Chen, Tao; Wen, Jiaolin; Wang, Wenwen; Chen, Lijuan


    The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa) methoxy poly(ethylene glycol) methyl ether (mPEG) to gambogic acid (GA-mPEG₂₀₀₀) through an ester linkage and characterized by (1)H nuclear magnetic resonance. The GA-mPEG₂₀₀₀ conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG₂₀₀₀ micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazo l-2-yl)-2,5 diphenyl tetrazolium bromide) tests demonstrated that the GA-mPEG₂₀₀₀ micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG₂₀₀₀ micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG₂₀₀₀ micelles may have promising applications in tumor therapy.


    Shweta P. Alai et al.


    Full Text Available There are various drugs used in daily life. Some of them show hazardous effect on various organs and some of them shows even lethal effect. Such drugs are required to banned. One of them is Etizolam (marketed under the brand name Sedekopan, Pasaden or Depas is a drug which is a thiebenzothiodiazepines analog. The aim of this work is done to compare the effect of administration of the etizolam drug at (Zero-day before incubation and at the (5-day first week of incubation, to get an idea about the extent of the teratogenic effect of this drug on the development of chick embryo. So that morphological and biochemical studies were done on the chick embryo of 8- and 16-days old chick embryos treated with (0.5mg/ml egg of etizolam on the (zero and 5-th days of incubation. Etizolam caused abnormality in concentration dependent manner. Enlarged remains of primitive streak was seen at 0.1mg/ml and o.3mg/ml concentration of Etizolam embryo dies. Etizolam inhibit development of somites of the development of 5-day at of incubation also it does not allow the development of notochord. The toxic effects of the drug was seen also more at 16-days treated chick embryos and the drug induced death of chick embryo at both 8- and 16-days treated with 0.1mg/ml and o.3mg/ml. The conclusion from this study was the etizolam drug has dangerous effects on tissues and with powerful toxicity on the cells, because the drug absorbed rapidly with peak plasma levels achieved between 30 minutes and 2 hours and has a mean elimination half life of about 3 and a half hours.

  18. Long-term safety and effectiveness of pramipexole in tetrahydrobiopterin deficiency.

    Porta, Francesco; Ponzone, Alberto; Spada, Marco


    Tetrahydrobiopterin (BH4) deficiencies are inherited neuro-metabolic disorders leading to monoamine neurotransmitters deficiency. An individualized replacement therapy with neurotransmitters precursors is necessary to restore dopaminergic and serotoninergic homeostasis. The correction of dopaminergic tone is complicated, like in Parkinson disease, by l-dopa short half-life and adverse effects. To improve this picture, since 2009 we introduced the non-ergot dopamine agonist pramipexole as an adjunct to l-dopa therapy in the treatment of the most common causes of BH4 deficiency, 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency and dihydropteridine reductase (DHPR) deficiency. In the short-term period, this approach allowed substantial clinical advantages in affected patients, with amelioration and stabilization of the clinical picture on twice daily treatment administration and no adverse effect. Here we describe the long-term clinical follow-up (83 ± 24 months) of seven patients with BH4 deficiency treated with pramipexole. After a period of good clinical compensation (34 ± 1 months), different impulse control disorders (gambling, compulsive buying, and hypersexuality) were observed in three patients treated with high-dose pramipexole (0.030-0.033 mg/kg/day) beyond adolescence. These psychiatric adverse effects promptly disappeared after curtailing pramipexole dose by 50-60%. Low-dose pramipexole therapy has been safe and effective in the long-term period in all treated patients (59 ± 9 months). High-dose pramipexole therapy in BH4 deficiency can be complicated, like in Parkinson disease, by psychiatric adverse effects. Low-dose pramipexole therapy (∼0.010 mg/kg/day) has been safe and clinically effective on long-term follow-up, representing a helpful therapeutic option in patients with BH4 deficiency.

  19. Thermal effects of impact bombardments on Noachian Mars

    Abramov, Oleg; Mojzsis, Stephen J.


    Noachian (prior to ca. 3700 Ma) terranes are the oldest and most heavily cratered landscapes on Mars, with crater densities comparable to the ancient highlands of the Moon and Mercury. Intense early cratering affected Mars by melting and fracturing its crust, draping large areas in impact ejecta, generating regional-scale hydrothermal systems, and increasing atmospheric pressure (and thereby, temperature) to periodically re-start an otherwise moribund hydrological cycle. Post primary-accretionary bombardment scenarios that shaped early Mars can be imagined in two ways: either as a simple exponential decay with an approximately 100 Myr half-life, or as a "sawtooth" timeline characterized by both faster-than-exponential decay from primary accretion and relatively lower total delivered mass. Indications are that a late bombardment spike was superposed on an otherwise broadly monotonic decline subsequent to primary accretion, of which two types are investigated: a classical "Late Heavy Bombardment" (LHB) peak of impactors centered at ca. 3900 Ma that lasted 100 Myr, and a protracted bombardment typified by a sudden increase in impactor flux at ca. 4100-4200 Ma with a correspondingly longer decay time (≤400 Myr). Numerical models for each of the four bombardment scenarios cited above show that the martian crust mostly escaped exogenic melting from bombardment. We find that depending on the chosen scenario, other physical effects of impacts were more important than melt generation. Model output shows that between 10 and 100% of the Noachian surface was covered by impact craters and blanketed in resultant (hot) ejecta. If early Mars was generally arid and cold, impact-induced heating punctuated this surface state by intermittently destabilizing the near-subsurface cryosphere to generate regional-scale hydrothermal systems. Rather than being deleterious to the proclivity of Noachian Mars to host an emergent biosphere, this intense early impact environment instead

  20. Cover Crops Effects on Soil Chemical Properties and Onion Yield

    Rodolfo Assis de Oliveira


    Full Text Available ABSTRACT Cover crops contribute to nutrient cycling and may improve soil chemical properties and, consequently, increase crop yield. The aim of this study was to evaluate cover crop residue decomposition and nutrient release, and the effects of these plants on soil chemical properties and on onion (Allium cepa L. yield in a no-tillage system. The experiment was carried out in an Inceptisol in southern Brazil, where cover crops were sown in April 2012 and 2013. In July 2013, shoots of weeds (WD, black oats (BO, rye (RY, oilseed radish (RD, oilseed radish + black oats (RD + BO, and oilseed radish + rye (RD + RY were cut at ground level and part of these material from each treatment was placed in litter bags. The litter bags were distributed on the soil surface and were collected at 0, 30, 45, 60, 75, and 90 days after distribution (DAD. The residues in the litter bags were dried, weighed, and ground, and then analyzed to quantify lignin, cellulose, non-structural biomass, total organic carbon (TOC, N, P, K, Ca, and Mg. In November 2012 and 2013, onion crops were harvested to quantify yield, and bulbs were classified according to diameter, and the number of rotted and flowering bulbs was determined. Soil in the 0.00-0.10 m layer was collected for chemical analysis before transplanting and after harvesting onion in December 2012 and 2013. The rye plant residues presented the highest half-life and they released less nutrients until 90 DAD. The great permanence of rye residue was considered a protection to soil surface, the opposite was observed with spontaneous vegetation. The cultivation and addition of dry residue of cover crops increased the onion yield at 2.5 Mg ha-1.

  1. Monitoring the effects of exposure to lead and cadmium in working and living environment through standard biochemical blood parameters and liver endonucleases activity

    Nikolić Ružica S.


    Full Text Available Heavy metals as pollutants in the working and living environment are a serious health and environmental problem because they are toxic, non-biodegradable, accumulate in living systems and have a long half-life in soil. Sources of lead contamination are combustion products in the chemical industry and metallurgy, industrial waste water, landfills, traffic etc. Lead enters into the body via the food chain and drinking water. In the body lead is deposited in the liver, kidneys, brain and mineral tissues. Excretion of lead causes damage to the epithelial cells of certain organs. High level exposure to cadmium is usually the result of environmental pollution by human activities. Exposure to cadmium can lead to acute and chronic tissue damage of various organs, including liver and kidneys in humans and in animals. In this paper we analyzed the effects of lead and cadmium exposure, in working and living environment, on the model system of experimental animals, particularly the activity of certain liver enzymes, acid and alkaline DNase, and standard biochemical blood parameters. The study showed that lead and cadmium significantly affect the protein content, red blood cells, hemoglobin and hematocrit, and the activity of liver enzymes. This harmful effect of this toxic metal can be reduced by the supplements.

  2. Cyclodextrin-Complexed Ocimum basilicum Leaves Essential Oil Increases Fos Protein Expression in the Central Nervous System and Produce an Antihyperalgesic Effect in Animal Models for Fibromyalgia

    Simone S. Nascimento


    Full Text Available O. basilicum leaves produce essential oils (LEO rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD, on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o., LEO (25 mg/kg, p.o., tramadol (TRM 4 mg/kg, i.p. or vehicle (saline, and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey, motor coordination (Rota-rod and muscle strength (Grip Strength Metter in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC, thermogravimetry/derivate thermogravimetry (TG/DTG and infrared absorption spectroscopy (FTIR curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

  3. Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases Fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia.

    Nascimento, Simone S; Araújo, Adriano A S; Brito, Renan G; Serafini, Mairim R; Menezes, Paula P; DeSantana, Josimari M; Lucca, Waldecy; Alves, Pericles B; Blank, Arie F; Oliveira, Rita C M; Oliveira, Aldeidia P; Albuquerque, Ricardo L C; Almeida, Jackson R G S; Quintans, Lucindo J


    O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

  4. Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics.

    Gurley, Bill J; Swain, Ashley; Williams, D Keith; Barone, Gary; Battu, Sunil K


    Concomitant administration of botanical supplements with drugs that are P-glycoprotein (P-gp) substrates may produce clinically significant herb-drug interactions. This study evaluated the effects of St. John's wort and Echinacea on the pharmacokinetics of digoxin, a recognized P-gp substrate. Eighteen healthy volunteers were randomly assigned to receive a standardized St. John's wort (300 mg three times daily) or Echinacea (267 mg three times daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (300 mg twice daily, 7 days) and clarithromycin (500 mg twice daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin 0.25 mg) was administered orally before and after each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), elimination half-life, and maximum serum concentration were used to assess the effects of St. John's wort, Echinacea, rifampin, and clarithromycin on digoxin disposition. St. John's wort and rifampin both produced significant reductions (p St. John's wort than with Echinacea.

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



    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

  6. Development of Transdermal Ondansetron Hydrochloride for the ...


    formulations were evaluated for patch thickness, tensile strength, moisture content, water absorption capacity and drug ... undesirable side effects, high clearance, short half-life, and low ..... Produced by Hot-Melt Extrusion. Pharmaceutical.

  7. Effective dose to immuno-PET patients due to metastable impurities in cyclotron produced zirconium-89

    Alfuraih, Abdulrahman; Alzimami, Khalid; Ma, Andy K.; Alghamdi, Ali; Al Jammaz, Ibrahim


    Immuno-PET is a nuclear medicine technique that combines positron emission tommography (PET) with radio-labeled monoclonal antibodies (mAbs) for tumor characterization and therapy. Zirconium-89 (89Zr) is an emerging radionuclide for immuno-PET imaging. Its long half-life (78.4 h) gives ample time for the production, the administering and the patient uptake of the tagged radiopharmaceutical. Furthermore, the nuclides will remain in the tumor cells after the mAbs are catabolized so that time series studies are possible without incurring further administration of radiopharmarceuticals. 89Zr can be produced in medical cyclotrons by bombarding an yttrium-89 (89Y) target with a proton beam through the 89Y(p,n)89Zr reaction. In this study, we estimated the effective dose to the head and neck cancer patients undergoing 89Zr-based immune-PET procedures. The production of 89Zr and the impurities from proton irradiation of the 89Y target in a cyclotron was calculated with the Monte Carlo code MCNPX and the nuclear reaction code TALYS. The cumulated activities of the Zr isotopes were derived from real patient data in literature and the effective doses were estimated using the MIRD specific absorbed fraction formalism. The estimated effective dose from 89Zr is 0.5±0.2 mSv/MBq. The highest organ dose is 1.8±0.2 mSv/MBq in the liver. These values are in agreement with those reported in literature. The effective dose from 89mZr is about 0.2-0.3% of the 89Zr dose in the worst case. Since the ratio of 89mZr to 89Zr depends on the cooling time as well as the irradiation details, contaminant dose estimation is an important aspect in optimizing the cyclotron irradiation geometry, energy and time.

  8. Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

    Frederickson Martyn


    Full Text Available Abstract Background Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior. Results We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle. Conclusion Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal

  9. Prosocial effects of oxytocin in two mouse models of autism spectrum disorders.

    Teng, Brian L; Nonneman, Randal J; Agster, Kara L; Nikolova, Viktoriya D; Davis, Tamara T; Riddick, Natallia V; Baker, Lorinda K; Pedersen, Cort A; Jarstfer, Michael B; Moy, Sheryl S


    Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs). However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier. In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens. This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms. Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens. Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J. Increased sociability was observed 24 h following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1-2 weeks post-treatment in C58/J. Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test. This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype. These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin.

  10. Prediction of a potentially effective dose in humans for BAY 60–5521, a potent inhibitor of cholesteryl ester transfer protein (CETP) by allometric species scaling and combined pharmacodynamic and physiologically-based pharmacokinetic modelling

    Weber, Olaf; Willmann, Stefan; Bischoff, Hilmar; Li, Volkhart; Vakalopoulos, Alexandros; Lustig, Klemens; Hafner, Frank-Thorsten; Heinig, Roland; Schmeck, Carsten; Buehner, Klaus


    AIMS The purpose of this work was to support the prediction of a potentially effective dose for the CETP-inhibitor, BAY 60–5521, in humans. METHODS A combination of allometric scaling of the pharmacokinetics of the CETP-inhibitor BAY 60–5521 with pharmacodynamic studies in CETP-transgenic mice and in human plasma with physiologically-based pharmacokinetic (PBPK) modelling was used to support the selection of the first-in-man dose. RESULTS The PBPK approach predicts a greater extent of distribution for BAY 60–5521 in humans compared with the allometric scaling method as reflected by a larger predicted volume of distribution and longer elimination half-life. The combined approach led to an estimate of a potentially effective dose for BAY 60–5521 of 51 mg in humans. CONCLUSION The approach described in this paper supported the prediction of a potentially effective dose for the CETP-inhibitor BAY 60–5521 in humans. Confirmation of the dose estimate was obtained in a first-in-man study. PMID:21762205

  11. Pharmacodynamic effect of enrofloxacin against Aeromonas hydrophila in vitro pharmacokinetic model%体外药动模型中恩诺沙星对嗜水气单胞菌的药动及药效研究

    陈俭清; 卢彤岩


    为降低嗜水气单胞菌耐药菌株的产生速度,延长恩诺沙星在水产动物上的应用年限,通过建立体外模型的方法,研究恩诺沙星对嗜水气单胞菌的药动-药效(PK-PD)参数.在消除半衰期为100 h的模型内,2 MIC(最小抑菌浓度)的恩诺沙星对嗜水气单胞菌能够抑制6 h,6 h后细菌出现再生长;4、8和16 MIC对嗜水气单胞菌能够起到持续的抑制作用.在消除半衰期为168 h的模型内,2 MIC的恩诺沙星对嗜水气单胞菌能够抑制6 h,6 h后细菌出现再生长;4、8和16 MIC对嗜水气单胞菌能够起到持续的抑制作用.结果表明,当AUC_(0→24)/MIC>75.24±13.24,C_(max)/MIC>4.10±0.12时,恩诺沙星对嗜水气单胞菌能够起到持续的抑制作用.%The purposes of this research is to decrease the occurrence speed of resistant Aeromonas hydrophila and prolong the time limit of enrofloxacin application on aquatic creature. By using in vitro pharmacokinetic model, PK-PD parameter of Aeromonas hydrophila against enrofloxacin was studied. In the in vitro model with elimination half-life of 100 h, Aeromonas hydrophila was inhibited for 6 h by 2 MIC enrofloxacin and was continuously inhibited in the entire experiment period of 24 h by 4, 8 and 16 MIC enrofloxacin. In the in vitro model with elimination half-life of 168 h, the inhibitation effect of 2 MIC enrofloxacin on Aeromonas hydrophila lasted for 6 h and the bacteria regrew after that. 4, 8 and 16 MIC enrofloxacin showed continously inhabitative action on Aeromonas hydrophila. It concluded that con-tinous inhabitation of Aeromonas hydrophila by enrofloxacin could be achieved at the condition of AUC_(0→24)/ MIC>75.24±13.24, C_(max)/MIC>4.10±0.12.

  12. The effect of rectal ozone on the portal vein oxygenation and pharmacokinetics of propranolol in liver cirrhosis (a preliminary human study).

    Zaky, Saad; Fouad, Ehab Ahmad; Kotb, Hassan Ibrahim Mohamad


    The aim of this study was to investigate the effect of rectal ozone on portal vein oxygenation and the pharmacokinetic changes of propranolol in patients with liver cirrhosis. Fifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80mg on the morning of day 1 after overnight fasting. Blood samples were collected at fixed time intervals for 24h. Patients were given 12 sessions of rectal ozone of 300ml of 40% ozone/oxygen mixture. On day 14 another oral dose of 80mg propranolol was given and blood samples were collected as on day 1. Plasma concentrations of propranolol were measured by HPLC. Portal vein oxygen tension and saturation were measured before and after rectal ozone. Plasma concentrations of propranolol were reduced after ozone therapy with pronounced decreases in the maximum plasma concentration and the area under the plasma concentration-time curve. The changes were consistent with a decrease in propranolol bioavailability. There was a decrease in the elimination half-life and mean residence time. Portal vein oxygenation significantly increased after rectal ozone. The changes in the pharmacokinetics of propranolol probably reflect an increase in the rate and extent of its metabolism resulting from improved portal vein oxygenation attributable to the ozone therapy. The present work highlights that ozone can be an alternative medical measure to improve portal vein oxygenation in liver cirrhosis. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  13. The effect of microwave pretreatment of seeds on the stability and degradation kinetics of phenolic compounds in rapeseed oil during long-term storage.

    Rękas, Agnieszka; Ścibisz, Iwona; Siger, Aleksander; Wroniak, Małgorzata


    Storage stability and degradation kinetics of phenolic compounds in rapeseed oil pressed from microwave treated seeds (0, 2, 4, 6, 8, 10min, 800W) during long-term storage (12months) at a temperature of 20°C was discussed in the current study. The dominant phenolic compound detected in rapeseed oil was canolol, followed by minor amounts of free phenolic acids and sinapine. The most pronounced effect of seeds microwaving was noted for canolol formation - after 10-min exposure the quantity of this compound was approximately 63-fold higher than in control oil. The degradation of phenolics during storage displayed pseudo first-order kinetics. Differences in the initial degradation rate (r0) demonstrated significant impact of the period of seeds microwave exposure on the degradation rates of phenolic compounds. Results of the half-life calculation (t1/2) showed that the storage stability of phenolic compounds was higher in oils produced from microwave treated rapeseeds than in control oil.

  14. Effects of food and gender on the pharmacokinetics of rhein and emodin in rats after oral dosing with Da-Cheng-Qi decoction.

    Gong, HanLin; Tang, WenFu; Wang, Hong; Xia, Qing; Huang, Xi


    Da-Cheng-Qi decoction (DCQD), a traditional Chinese medicine preparation used to treat digestive diseases, is composed of dahuang (Rheum officinale Baill, Polygonaceae), houpu (Magnolia officinalis Rehd., Magnoliaceae), zhishi (Citrus aurantium L, Rutaceae) and mangxiao (sodium sulphate). Rhein and emodin are the major active components of Rheum officinale Baill. To investigate the effects of food and gender on the plasma concentrations of rhein and emodin after oral administration of DCQD, a rapid high-performance liquid chromatographic method was developed and validated. A reversed phase C(18) column (150 × 4.6 mm) and a mobile phase of methanol and 0.2% acetic acid (78:22, v/v) were employed with ultraviolet detection at 254 nm. Feeding was observed to decrease the absorption of rhein and emodin in rats receiving DCQD orally. No evidence for gender-based differences in the pharmacokinetics of rhein was observed. However, the half-life and area under the concentration-time curve for emodin differed significantly between male and female rats. Because food intake and gender are anticipated to influence the pharmacokinetics of DCQD in human subjects, it is recommended that oral doses of DCQD be reduced in fasting subjects and that female patients receive lower oral doses compared with male patients.

  15. Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV.

    Tebas, Pablo; Stein, David; Binder-Scholl, Gwendolyn; Mukherjee, Rithun; Brady, Troy; Rebello, Tessio; Humeau, Laurent; Kalos, Michael; Papasavvas, Emmanouil; Montaner, Luis J; Schullery, Daniel; Shaheen, Farida; Brennan, Andrea L; Zheng, Zhaohui; Cotte, Julio; Slepushkin, Vladimir; Veloso, Elizabeth; Mackley, Adonna; Hwang, Wei-Ting; Aberra, Faten; Zhan, Jenny; Boyer, Jean; Collman, Ronald G; Bushman, Frederic D; Levine, Bruce L; June, Carl H


    We report the safety and tolerability of 87 infusions of lentiviral vector–modified autologous CD4 T cells (VRX496-T; trade name, Lexgenleucel-T) in 17 HIV patients with well-controlled viremia. Antiviral effects were studied during analytic treatment interruption in a subset of 13 patients. VRX496-T was associated with a decrease in viral load set points in 6 of 8 subjects (P = .08). In addition, A → G transitions were enriched in HIV sequences after infusion, which is consistent with a model in which transduced CD4 T cells exert antisense-mediated genetic pressure on HIV during infection. Engraftment of vector-modified CD4 T cells was measured in gut-associated lymphoid tissue and was correlated with engraftment in blood. The engraftment half-life in the blood was approximately 5 weeks, with stable persistence in some patients for up to 5 years. Conditional replication of VRX496 was detected periodically through 1 year after infusion. No evidence of clonal selection of lentiviral vector–transduced T cells or integration enrichment near oncogenes was detected. This is the first demonstration that gene-modified cells can exert genetic pressure on HIV. We conclude that gene-modified T cells have the potential to decrease the fitness of HIV-1 and conditionally replicative lentiviral vectors have a promising safety profile in T cells.

  16. Rejection of randomly coinciding events in Li$_2$$^{100}$MoO$_4$ scintillating bolometers using light detectors based on the Neganov-Luke effect

    Chernyak, D M; Dumoulin, L; Giuliani, A; Mancuso, M; de Marcillac, P; Marnieros, S; Nones, C; Olivieri, E; Poda, D V; Tretyak, V I


    Random coincidences of nuclear events can be one of the main background sources in low-temperature calorimetric experiments looking for neutrinoless double-beta decay, especially in those searches based on scintillating bolometers embedding the promising double-beta candidate $^{100}$Mo, because of the relatively short half-life of the two-neutrino double-beta decay of this nucleus. We show in this work that randomly coinciding events of the two-neutrino double decay of $^{100}$Mo in enriched Li$_2$$^{100}$MoO$_4$ detectors can be effectively discriminated by pulse-shape analysis in the light channel if the scintillating bolometer is provided with a Neganov-Luke light detector, which can improve the signal-to-noise ratio by a large factor, assumed here at the level of $\\sim 750$ on the basis of preliminary experimental results obtained with these devices. The achieved pile-up rejection efficiency results in a very low contribution, of the order of $\\sim 6\\times10^{-5}$ counts/(keV$\\cdot$kg$\\cdot$y), to the ba...

  17. The Effect of Tween® Surfactants in Sol-Gel Processing for the Production of TiO2 Thin Films

    Ann-Louise Anderson


    Full Text Available Titanium dioxide thin films were deposited using a Tween® surfactant modified non-aqueous sol-gel method onto fluorine doped tin oxide glass substrates. The surfactant concentration and type in the sols was varied as well as the number of deposited layers. The as deposited thin films were annealed at 500 °C for 15 min before characterisation and photocatalytic testing with resazurin intelligent ink. The films were characterised using scanning electron microscopy, atomic force microscopy, X-ray diffraction, Raman spectroscopy and UV-Vis spectroscopy. Photocatalytic activity of the films was evaluated using a resazurin dye-ink test and the hydrophilicity of the films was analysed by water-contact angles measurements. Characterisation and photocatalytic testing has shown that the addition of surfactant in varying types and concentrations had a significant effect on the resulting thin film microstructure, such as changing the average particle size from 130 to 25 nm, and increasing the average root mean square roughness from 11 to 350 nm. Such structural changes have resulted in an enhanced photocatalytic performance for the thin films, with an observed reduction in dye half-life from 16.5 to three minutes.

  18. Effective stimulation of growth in MCF-7 human breast cancer cells by inhibition of syntaxin18 by external guide sequence and ribonuclease P.

    Bassett, Tyler; Harpur, Brock; Poon, Ho Y; Kuo, Kuo-Hsing; Lee, Chow H


    Syntaxin18 (Stx18) is an endoplasmic reticulum (ER)-membrane bound SNARE protein involved in membrane trafficking between the ER and Golgi as well as in phagocytosis. Stx18 has also been shown to physically interact with proteins involved in the cell cycle and apoptosis. These findings suggest the possible role of Stx18 in regulating cell growth. In this study, we used theoretically designed external guide sequence molecule which utilizes RNase P to cleave Stx18 mRNA and down-regulate Stx18 levels in MCF-7 human breast cancer cells. We showed that down-regulation of Stx18 leads to significant enhancement of growth in MCF-7 cells. Consistent with this finding was the observation that over-expression of Stx18 using the CMV promoter led to suppression of cell growth. Over-expressing Stx18 had no effect on c-myc mRNA expression and half-life, suggesting that the mechanism does not involve control at the transcriptional and post-transcriptional level of the c-myc gene. Finally, we showed that Stx18 is over-expressed in clinical human breast cancer. Overall, this study showed that Stx18 plays a role in the growth of human breast cancer cells and provided the basis for further investigation in determining whether it can be used as a prognostic marker and as a molecular target in the treatment of breast cancer.

  19. Investigation by response surface methodology of the combined effect of pH and composition of water-methanol mixtures on the stability of curcuminoids.

    D'Archivio, Angelo Antonio; Maggi, Maria Anna


    Response surface methodology, coupled to a full factorial three-level experimental design, was applied to investigate the combined influence of pH (between 7.0 and 8.6) and composition of methanol-water mixtures (between 30 and 70% v/v of methanol content) on the stability of curcumin and its analogues demethoxycurcumin and bisdemethoxycurcumin. The response plots revealed that addition of methanol noticeably improved the stability of curcuminoids, this effect being both pH- and structure-dependent. In the central point of the experimental domain, half-life times of curcumin, demethoxycurcumin and bisdemethoxycurcumin were 3.8±0.2, 27±2 and 251±17h, respectively. Stability of curcuminoids increased at lower pH and higher methanol content and decreased in the opposite vertex of the experimental domain. These results can be interpreted by assuming that addition of methanol to water produces a different variation of pH of the medium and apparent pKa values of the ionisable groups of curcuminoids.

  20. Evaluation of the effectiveness and safety of the thermo-treatment process to dispose of recombinant DNA waste from biological research laboratories.

    Li, Meng-Nan; Zheng, Guang-Hong; Wang, Lei; Xiao, Wei; Fu, Xiao-Hua; Le, Yi-Quan; Ren, Da-Ming


    The discharge of recombinant DNA waste from biological laboratories into the eco-system may be one of the pathways resulting in horizontal gene transfer or "gene pollution". Heating at 100 degrees C for 5-10 min is a common method for treating recombinant DNA waste in biological research laboratories in China. In this study, we evaluated the effectiveness and the safety of the thermo-treatment method in the disposal of recombinant DNA waste. Quantitative PCR, plasmid transformation and electrophoresis technology were used to evaluate the decay/denaturation efficiency during the thermo-treatment process of recombinant plasmid, pET-28b. Results showed that prolonging thermo-treatment time could improve decay efficiency of the plasmid, and its decay half-life was 2.7-4.0 min during the thermo-treatment at 100 degrees C. However, after 30 min of thermo-treatment some transforming activity remained. Higher ionic strength could protect recombinant plasmid from decay during the treatment process. These results indicate that thermo-treatment at 100 degrees C cannot decay and inactivate pET-28b completely. In addition, preliminary results showed that thermo-treated recombinant plasmids were not degraded completely in a short period when they were discharged into an aquatic environment. This implies that when thermo-treated recombinant DNAs are discharged into the eco-system, they may have enough time to re-nature and transform, thus resulting in gene diffusion.

  1. Cost-effectiveness analysis of darbepoetin after switch from epoetin-beta in patients on hemodialysis: an Italian single-center retrospective study

    Mario Eandi


    Full Text Available Darbepoetin (DARB, a human erythropoietin with improved pharmacological parameters (longer half life and a dose-response relationship independent from the route of administration is a new treatment option for chronic nephropathy-induced anemia that in many Italian dialysis centers is substituting older erythropoietins, mainly due to greater ease of use. At current prices and at the theoretical and recommended 200:1 dose conversion factor, DARB pharmaceutical cost ranges from –9% to +17% of EPO cost. In this monocentric study, real drug consumption and related actual costs of a pre-switch semester with EPO were analysed and compared to the first two post-switch semesters with DARB therapy. Furthermore, erythropoetic response was recorded and related to drug exposition levels, in order to establish a real life EPO:DARB dose conversion factor. In this experience, the conversion factor was estimated in at least 250-280:1, depending on the method adopted for the estimation. The initial dose, chosen on the basis of the recommended conversion factor, induced an excessive erythropoietic response, which was generally followed by a dose reduction and successive titration to target desired Hb levels, generating the spiraliform dose-response curve associated with delayed feed-back mechanisms. The pharmacoeconomical analysis, conducted in the perspective of the public health service, indicated that the choice of substituting DARB for EPO in the treatment of chronic kidney failure-associated anemia is univocally convenient, the former being less costly and more effective.

  2. [Effects of coffee and caffeine on fertility, reproduction, lactation, and development. Review of human and animal data].

    Nehlig, A; Debry, G


    In the present review, we have examined the effects of coffee ingestion on fertility, reproduction, lactation and development. The potential effects of coffee consumption on fertility, spontaneous abortion and prematurity are not clearly established but appear to be quite limited. In rodents, caffeine can induce malformations but this effect appears in general at doses never encountered in humans. Indeed, as soon as the quantity of caffeine is divided over the day, as is the case for human consumption, the teratogenic effect of caffeine disappears in rodents. Coffee ingested during gestation induces a dose-dependent decrease in birth weight, but usually only when ingested amounts are high (i.e. more than 7 cups/day), whereas coffee has no effect at moderate doses. Caffeine consumption during gestation affects hematologic parameters of the new-born infant or rat. In animals, caffeine induces long-term consequences on sleep, locomotion, learning abilities, emotivity and anxiety, whereas, in children, the effects of early exposure to coffee and caffeine on behavior are not clearly established. The quantities of caffeine found in maternal milk vary with authors, but it appears clearly that caffeine does not change maternal milk composition and has a tendency to stimule milk production. In conclusion to this review, it appears that maternal coffee or caffeine consumption during gestation and/or lactation does not seem to have measurable consequences on the fetus of the newborn, as long as ingested quantities remain moderate. Therefore, pregnant mothers should be advised to limit their coffee and caffeine intake to 300 mg caffeine/day (i.e. 2-3 cups of coffee or 2.5-3 l of coke) especially because of the increase of caffeine half-life during the third trimester of pregnancy and in the neonate.

  3. Comparison of Adenosine Stress Myocardial Perfusion Scintigraphy and Oral Dipyridamole Stress Myocardial Perfusion Scintigraphy for Hemodynamic Changes and Adverse Effects

    Ahmet Yanarateş


    Full Text Available Objective: Similar effects can be achieved during stress myocardial perfusion scintigraphy (MPS using pharmacological agents to create cardiac stress for patients who are unable to exercise. In our study, we aimed to show the hemodynamic changes and adverse effects caused by adenosine and to compare the results with dipyridamole stress MPS. Materials and Methods: Sixty-five patients with suspected coronary artery disease were included in our study. Fifty patients in whom stress MPS with intravenous adenosine was performed (group A and 15 patients who underwent oral dipyridamole stress MPS (group B were retrospectively evaluated. During the test, blood pressure measurements and electrocardiographic follow-up were performed in all patients and side effects were noted. Results: At least one side effect occurred in 68% of the group A and in 46% of the group B patients. There was no statistically significant difference between the two groups in terms of side effects that occurred during the pharmacological stress. During the maximum stress, there was an increase of 15.80±11.60 beats/min in heart beats in group A and 5.53±4.54 beats/min in group B. There was a statistically significant difference between the groups in terms of heart rate increase per minute. When we compared reduction in systolic blood pressure and diastolic blood pressure, there was no statistically significant difference between the two groups. Conclusion: Although side effects are more often seen with adenosine, rapid decline in complaints was observed when adenosine infusion was terminated and there was no need for patient follow-up due to short half life of adenosine. We believe that these favourable advantages will increase the use of adenosine in clinical practice.

  4. Effects of Detrital Subsidies on Soft-Sediment Ecosystem Function Are Transient and Source-Dependent.

    Rebecca V Gladstone-Gallagher

    Full Text Available Detrital subsidies from marine macrophytes are prevalent in temperate estuaries, and their role in structuring benthic macrofaunal communities is well documented, but the resulting impact on ecosystem function is not understood. We conducted a field experiment to test the effects of detrital decay on soft-sediment primary production, community metabolism and nutrient regeneration (measures of ecosystem function. Twenty four (2 m2 plots were established on an intertidal sandflat, to which we added 0 or 220 g DW m-2 of detritus from either mangroves (Avicennia marina, seagrass (Zostera muelleri, or kelp (Ecklonia radiata (n = 6 plots per treatment. Then, after 4, 17 and 46 d we measured ecosystem function, macrofaunal community structure and sediment properties. We hypothesized that (1 detrital decay would stimulate benthic primary production either by supplying nutrients to the benthic macrophytes, or by altering the macrofaunal community; and (2 ecosystem responses would depend on the stage and rate of macrophyte decay (a function of source. Avicennia detritus decayed the slowest with a half-life (t50 of 46 d, while Zostera and Ecklonia had t50 values of 28 and 2.6 d, respectively. However, ecosystem responses were not related to these differences. Instead, we found transient effects (up to 17 d of Avicennia and Ecklonia detritus on benthic primary production, where initially (4 d these detrital sources suppressed primary production, but after 17 d, primary production was stimulated in Avicennia plots relative to controls. Other ecosystem function response variables and the macrofaunal community composition were not altered by the addition of detritus, but did vary with time. By sampling ecosystem function temporally, we were able to capture the in situ transient effects of detrital subsidies on important benthic ecosystem functions.

  5. Fluoxetine and sleep EEG: effects of a single dose, subchronic treatment, and discontinuation in healthy subjects.

    Feige, Bernd; Voderholzer, Ulrich; Riemann, Dieter; Dittmann, Ralf; Hohagen, Fritz; Berger, Mathias


    The goals of the current study were to evaluate whether a single dose of fluoxetine causes qualitatively different changes in sleep architecture and NREM sleep EEG than subchronic administration in healthy subjects and to determine degree and duration of such changes after the single dose and after discontinuation from subchronic administration. Our hypothesis was that subchronic intake should cause changes qualitatively different from the single dose and that such changes could be sufficiently long-lived to suggest the possibility of a dosing in intervals of several days. Ten healthy volunteers first took one single 60-mg dose of fluoxetine and a week later started to take a 40-mg dose every morning for three weeks. Sleep laboratory nights included two nights before and four nights after the single dose and every second night for two weeks after discontinuation from subchronic administration. The single dose caused only a slight increase in drug plasma concentrations but relatively clear changes in sleep structure. After discontinuation from subchronic administration, sleep quality indices normalized quickly (within 2-4 days), whereas REM latency and spectral power effects correlated with total SSRI plasma concentration and normalized more slowly, corresponding to the drug plasma half-life of about 10 days. The REM fraction of the sleep period showed a rebound, whereas the delta sleep ratio did not correlate with drug plasma levels and yet remained increased after the medication interval. Thus, the only qualitative difference seen between acute and subchronic medication was the initial sleep disturbance. REM latency and especially the delta sleep ratio remained increased for several days after discontinuation from subchronic administration, indicating the possibility of a less-than-daily maintenance medication after an initial daily interval. Finally, the pattern of change observed for the delta sleep ratio indicates that it may be due to secondary, adaptive

  6. Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels.

    Qijing Chen

    Full Text Available Large conductance Ca2+-activated potassium channels (BK are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α and BK (α+β1 currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1. Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms.

  7. Effects of E2HSA, a Long-Acting Glucagon Like Peptide-1 Receptor Agonist, on Glycemic Control and Beta Cell Function in Spontaneous Diabetic db/db Mice

    Shaocong Hou


    Full Text Available Glucagon like peptide-1 (GLP-1 receptor agonists such as exendin-4 have been widely used but their short half-life limits their therapeutic value. The recombinant protein, E2HSA, is a novel, long-acting GLP-1 receptor agonist generated by the fusion of exendin-4 with human serum albumin. In mouse pancreatic NIT-1 cells, E2HSA activated GLP-1 receptor with similar efficacy as exendin-4. After single-dose administration in ICR mice, E2HSA showed prolonged glucose lowering effects which lasted up to four days and extended inhibition on gastric emptying for at least 72 hours. Chronic E2HSA treatment in db/db mice significantly improved glucose tolerance, reduced elevated nonfasting and fasting plasma glucose levels, and also decreased HbA1c levels. E2HSA also increased insulin secretion and decreased body weight and appetite. Furthermore, immunofluorescence analysis showed that E2HSA increased β-cell area, improved islet morphology, and reduced β-cell apoptosis. In accordance with the promotion of β-cell function and survival, E2HSA upregulated genes such as Irs2, Pdx-1, Nkx6.1, and MafA and downregulated the expression levels of FoxO1 and proapoptotic Bcl-2 family proteins. In conclusion, with prolonged glucose lowering effects and promoting β-cell function and survival, the fusion protein, E2HSA, is a promising new therapeutic for once weekly treatment of type 2 diabetes.

  8. Effects of E2HSA, a Long-Acting Glucagon Like Peptide-1 Receptor Agonist, on Glycemic Control and Beta Cell Function in Spontaneous Diabetic db/db Mice.

    Hou, Shaocong; Li, Caina; Huan, Yi; Liu, Shuainan; Liu, Quan; Sun, Sujuan; Jiang, Qian; Jia, Chunming; Shen, Zhufang


    Glucagon like peptide-1 (GLP-1) receptor agonists such as exendin-4 have been widely used but their short half-life limits their therapeutic value. The recombinant protein, E2HSA, is a novel, long-acting GLP-1 receptor agonist generated by the fusion of exendin-4 with human serum albumin. In mouse pancreatic NIT-1 cells, E2HSA activated GLP-1 receptor with similar efficacy as exendin-4. After single-dose administration in ICR mice, E2HSA showed prolonged glucose lowering effects which lasted up to four days and extended inhibition on gastric emptying for at least 72 hours. Chronic E2HSA treatment in db/db mice significantly improved glucose tolerance, reduced elevated nonfasting and fasting plasma glucose levels, and also decreased HbA1c levels. E2HSA also increased insulin secretion and decreased body weight and appetite. Furthermore, immunofluorescence analysis showed that E2HSA increased β-cell area, improved islet morphology, and reduced β-cell apoptosis. In accordance with the promotion of β-cell function and survival, E2HSA upregulated genes such as Irs2, Pdx-1, Nkx6.1, and MafA and downregulated the expression levels of FoxO1 and proapoptotic Bcl-2 family proteins. In conclusion, with prolonged glucose lowering effects and promoting β-cell function and survival, the fusion protein, E2HSA, is a promising new therapeutic for once weekly treatment of type 2 diabetes.

  9. Respiratory Effects of the Nociceptin/Orphanin FQ Peptide and Opioid Receptor Agonist, Cebranopadol, in Healthy Human Volunteers.

    Dahan, Albert; Boom, Merel; Sarton, Elise; Hay, Justin; Groeneveld, Geert Jan; Neukirchen, Meike; Bothmer, John; Aarts, Leon; Olofsen, Erik


    Cebranopadol is a novel strong analgesic that coactivates the nociceptin/orphanin FQ receptor and classical opioid receptors. There are indications that activation of the nociceptin/orphanin FQ receptor is related to ceiling in respiratory depression. In this phase 1 clinical trial, we performed a pharmacokinetic-pharmacodynamic study to quantify cebranopadol's respiratory effects. Twelve healthy male volunteers received 600 μg oral cebranopadol as a single dose. The following main endpoints were obtained at regular time intervals for 10 to 11 h after drug intake: ventilation at an elevated clamped end-tidal pressure of carbon dioxide, pain threshold and tolerance to a transcutaneous electrical stimulus train, and plasma cebranopadol concentrations. The data were analyzed using sigmoid Emax (respiration) and power (antinociception) models. Cebranopadol displayed typical opioid-like effects including miosis, analgesia, and respiratory depression. The blood-effect-site equilibration half-life for respiratory depression and analgesia was 1.2 ± 0.4 h (median ± standard error of the estimate) and 8.1 ± 2.5 h, respectively. The effect-site concentration causing 50% respiratory depression was 62 ± 4 pg/ml; the effect-site concentration causing 25% increase in currents to obtain pain threshold and tolerance was 97 ± 29 pg/ml. The model estimate for minimum ventilation was greater than zero at 4.9 ± 0.7 l/min (95% CI, 3.5 to 6.6 l/min). At the dose tested, cebranopadol produced respiratory depression with an estimate for minimum ventilation greater than 0 l/min. This is a major advantage over full μ-opioid receptor agonists that will produce apnea at high concentrations. Further clinical studies are needed to assess whether such behavior persists at higher doses.

  10. Effects of nanoscale quantum dots in male Chinese loaches (Misgurnus anguillicaudatus):Estrogenic interference action,toxicokinetics and oxidative stress


    Quantum dots (QDs) have received more and more attention as a novel example of nanocrystals due to their unique fluorescent characteristics. Recently, the toxicity and the potential environmental effects of QDs have become a research hotspot. In this work, in vivo endocrine disrupting effect, toxicokinetics and oxidative stress of QDs were characterized following the intraperitoneal dosing in Chinese loaches. Vitellogenin (Vtg) levels induced by E2 decreased significantly when administrated with the mixture of QDs and E2, which was consistent with the observations of histopathology in testes. The release of free Cd2+ from QDs and the non-specific adsorption of E2 by QDs might be the joint factors contributing to the inhibition of Vtg expression induced by E2 in the male Chinese loaches. In the muscle, bone, intestines, blood and testis, CdSe QDs reached the maximal concentration (Cmax) in approximately 1-h postinjection and subsequently presented downtrend with the prolonged time. Whereas, there were even increasing tendencies of CdSe QDs’ concentrations in the liver and kidney. It is educible that CdSe QDs can be persistent at least for 7 days, indicating the overall half-life of CdSe QDs in the fish body is very long. The measurement of hepatic superoxide dismutase (SOD) activity and reduced glutathione (GSH) content indicate that QDs have smaller effects on the antioxidative system of the organisms compared with free Cd2+ due to the effective prevention of the release of Cd by PEG coating of QDs. The comprehensive evaluation of QDs’ toxicity in the present study provides an essential and general framework towards more focused research on the elucidation of the biological effects of QDs in vivo.

  11. Effects of nanoscale quantum dots in male Chinese Ioaches (Misgurnus anguillicaudatus): Estrogenic interference action, toxicokinetics and oxidative stress

    LI HongCheng; LUO WenRu; TAO Yong; WU Yuan; LV XueFei; ZHOU QunFang; JIANG GuiBin


    Quantum dots (QDs) have received more and more attention as a novel example of nanocrystals due to their unique fluorescent characteristics. Recently, the toxicity and the potential environmental effects of QDs have become a research hotspot. In this work, in vivo endocrine disrupting effect, toxicokinetics and oxidative stress of QDs were characterized following the intraperitoneal dosing in Chinese Ioaches. Vitellogenin (Vtg) levels induced by E2 decreased significantly when administrated with the mixture of QDs and E2, which was consistent with the observations of histopathology in testes. The release of free Cd~(2+) from QDs and the non-specific adsorption of E2 by QDs might be the joint factors contributing to the inhibition of Vtg expression induced by E2 in the male Chinese Ioaches. In the muscle, bone, intestines, blood and testis, CdSe QDs reached the maximal concentration (Cmax) in approximately 1-h postinjection and subsequently presented downtrend with the prolonged time. Whereas, there were even increasing tendencies of CdSe ODs' concentrations in the liver and kidney. It is educible that CdSe QDs can be persistent at least for 7 days, indicating the overall half-life of CdSe QDs in the fish body is very long. The measurement of hepatic superoxide dismutase (SOD) activity and reduced glutathione (GSH) content indicate that QDs have smaller effects on the antioxidative system of the organisms compared with free Cd~(2+) due to the effective prevention of the release of Cd by PEG coating of QDs. The comprehensive evaluation of QDs' toxicity in the present study provides an essential and general framework towards more focused research on the elucidation of the biological effects of QDs in vivo.

  12. Clinical effectiveness of dolutegravir in the treatment of HIV/AIDS

    Taha H


    Full Text Available Huda Taha,1 Archik Das,2 Satyajit Das1,3 1Integrated Sexual Health Service Coventry and Warwickshire Partnership NHS Trust, Coventry, 2School of Medicine, Birmingham University, Birmingham, 3Coventry University, Coventry, UK Abstract: Dolutegravir (DTG is a second-generation integrase strand transfer inhibitor (INSTI, which has now been licensed to be used in different countries including the UK. Earlier studies have demonstrated that DTG when used with nucleoside backbone in treatment-naïve and -experienced patients has been well tolerated and demonstrated virological suppression comparable to other INSTIs and superiority against other first-line agents, including efavirenz and boosted protease inhibitors. Like other INSTIs, DTG uses separate metabolic pathways compared to other antiretrovirals and is a minor substrate for CYP-450. It does not appear to have a significant interaction with drugs, which uses the CYP-450 system. Nonetheless, it uses renal solute transporters that may potentially inhibit the transport of other drugs and can have an effect on the elimination of other drugs. However, the impact of this mechanism appears to be very minimal and insignificant clinically. The side effect profiles of DTG are similar to raltegravir and have been found to be well tolerated. DTG has a long plasma half-life and is suitable for once daily use without the need for a boosting agent. DTG has all the potential to be used as a first-line drug in combination with other nucleoside backbones, especially in the form of a single tablet in combination with abacavir and lamivudine. The purpose of this review article is to present the summary of the available key information about the clinical usefulness of DTG in the treatment of HIV infection. Keywords: dolutegravir, integrase inhibitors, HIV, antiretroviral, treatment

  13. Walnut kernel-like mesoporous silica nanoparticles as effective drug carrier for cancer therapy in vitro

    Ge, Kun; Ren, Huihui; Sun, Wentong; Zhao, Qi; Jia, Guang; Zang, Aimin; Zhang, Cuimiao; Zhang, Jinchao


    In drug delivery systems, nanocarriers could reduce the degradation and renal clearance of drugs, increase the half-life in the bloodstream and payload of drugs, control the release patterns, and improve the solubility of some insoluble drugs. In particular, mesoporous silica nanoparticles (MSNs) are considered to be attractive nanocarriers for application of delivery systems because of their large surface areas, large pore volume, tunable pore sizes, good biocompatibility, and the ease of surface functionalization. However, the large-scale synthesis of monodisperse MSNs that are smaller than 200 nm remains a challenge. In this study, monodisperse walnut kernel-like MSNs with diameters of approximately 100 nm were synthesized by a sol-gel route on a large scale. The morphology and structure of MSNs were characterized by scanning electron microscope, and transmission electron microscopy, N2 adsorption-desorption isotherms, Zeta potentials, and dynamic light scattering. Drug loading and release profile, cellular uptake, subcellular localization, and anticancer effect in vitro were further investigated. The results indicated that the loading efficiency of doxorubicinhydrochloride (DOX) into the MSNs was 57 %. The MSNs-DOX delivery system exhibited a drug-pronounced initial burst release within 12 h, followed by the slow sustained release of DOX molecules; moreover, MSNs could improve DOX release efficiency in acidic medium. Most free DOX was localized in the cytoplasm, whereas the MSNs-DOX was primarily distributed in lysosome. MSNs-DOX exhibited a potential anticancer effect against MCF-7, HeLa, and A549 cells in dose- and time-dependent manners. In summary, the as-synthesized MSNs may have well function as a promising drug carrier in drug delivery fields.

  14. Effects of Power Ultrasound on Stability of Cyanidin-3-glucoside Obtained from Blueberry

    Guang-Long Yao


    Full Text Available Power ultrasound (US could potentially be used in the food industry in the future. However, the extent of anthocyanin degradation by US requires investigation. Cyanidin-3-glucoside (Cy-3-glu obtained from blueberry extracts was used as research material to investigate the effect of power ultrasound on food processing of anthocyanin-rich raw materials. The effects of ultrasonic waves on the stability of Cy-3-glu and on the corresponding changes in UV-Vis spectrum and antioxidant activity were investigated, and the mechanisms of anthocyanin degradation induced by ultrasonic waves were discussed. To explore Cy-3-glu degradation in different environments, we kept the Cy-3-glu solution treated with ultrasonic waves in four concentrations (0%, 10%, 20%, and 50% of ethanol aqueous solutions to simulate water, beer, wine, and liquor storage environment according to the chemical kinetics method. Results show that the basic spectral characteristics of Cy-3-glu did not significantly change after power ultrasound cell crusher application at 30 °C. However, with anthocyanin degradation, the intensity of the peak for Cy-3-glu at 504 nm significantly decreased (p < 0.05. The degradation kinetics of Cy-3-glu by ultrasonic waves (200–500 W frequency fitted well to first-order reaction kinetics, and the degradation rate constant of Cy-3-glu under power ultrasound was considerably larger than that under thermal degradation (p < 0.05. The sensitivity of the anthocyanins of blueberry to temperature increased with increasing ethanol concentration, and the longest half-life was observed in 20% ethanol aqueous solution.

  15. Effect of buprenorphine on total intravenous anesthetic requirements during spine surgery.

    Khelemsky, Yury; Schauer, Jacob; Loo, Nathaniel


    Buprenorphine is a partial mu receptor agonist and kappa/delta antagonist commonly used for the treatment of opioid dependence or as an analgesic. It has a long plasma half-life and a high binding affinity for opioid receptors. This affinity is so high, that the effects are not easily antagonized by competitive antagonists, such as naloxone. The high affinity also prevents binding of other opioids, at commonly used clinical doses, to receptor sites - preventing their analgesic and likely minimum alveolar concentration (MAC) reducing benefits. This case report contrasts the anesthetic requirements of a patient undergoing emergency cervical spine surgery while taking buprenorphine with anesthetic requirements of the same patient undergoing a similar procedure after weaning of buprenorphine. Use of intraoperative neurophysiological monitoring prevented use of paralytics and inhalational anesthetics during both cases, therefore total intravenous anesthesia (TIVA) was maintained with propofol and remifentanil infusions. During the initial surgery, intraoperative patient movement could not be controlled with very high doses of propofol and remifentanil. The patient stopped moving in response to surgical stimulation only after the addition of a ketamine. Buprenorphine-naloxone was discontinued postoperatively. Five days later the patient underwent a similar cervical spine surgery. She had drastically reduced anesthetic requirements during this case, suggesting buprenorphine's profound effect on anesthetic dosing. This case report elegantly illustrates that discontinuation of buprenorphine is likely warranted for patients who present for major spine surgery, which necessitates the avoidance of volatile anesthetic and paralytic agents. The addition of ketamine may be necessary in patients maintained on buprenorphine in order to ensure a motionless surgical field.

  16. Non-analgesic effects of opioids: opioid-induced respiratory depression.

    Boom, Merel; Niesters, Marieke; Sarton, Elise; Aarts, Leon; Smith, Terry W; Dahan, Albert


    Opioids induce respiratory depression via activation of μ-opioid receptors at specific sites in the central nervous system including the pre-Bötzinger complex, a respiratory rhythm generating area in the pons. Full opioid agonists like morphine and fentanyl affect breathing with onset and offset profiles that are primarily determined by opioid transfer to the receptor site, while the effects of partial opioid agonists such as buprenorphine are governed by transfer to the receptor site together with receptor kinetics, in particular dissociation kinetics. Opioid-induced respiratory depression is potentially fatal but may be reversed by the opioid receptor antagonist naloxone, an agent with a short elimination half-life (30 min). The rate-limiting factor in naloxone-reversal of opioid effect is the receptor kinetics of the opioid agonists that requires reversal. Agents with slow dissociation kinetics (buprenorphine) require a continuous naloxone infusion while agents with rapid kinetics (fentanyl) will show complete reversal upon a single naloxone dose. Since naloxone is non-selective and will reverse analgesia as well, efforts are focused on the development of compounds that reverse opioid-induced respiratory depression without affecting analgesic efficacy. Such agents include ampakines and serotonin agonists which are aimed at selectively enhancing central respiratory drive. A novel approach is aimed at the reduction of respiratory depression from opioid-activation of (micro-)glia cells in the pons and brainstem using micro-glia cell stabilizers. Since this approach simultaneously enhances opioid analgesic efficacy it seems an attractive alternative to the classical reversal strategies with naloxone.

  17. Toxicokinetics and acute effects of MTBE and ETBE in male volunteers.

    Johanson, G; Nihlén, A; Löf, A


    Methyl tertiary butyl ether (MTBE) is widely used in gasoline as an oxygenator and octane enhancer. There is also an interest in using the ethyl tertiary butyl (ETBE) and methyl tertiary amyl (TAME) ethers. We measured the blood, water, and olive oil/air partition coefficients in vitro of MTBE, ETBE, TAME and tertiary butyl alcohol (TBA), a metabolite of MTBE and ETBE. The results indicate similar uptake and distribution behavior for the three ethers and a slight affinity for fatty tissues. The partition coefficients of TBA indicate that this metabolite is not excreted via the lungs to any great extent and that it is preferentially distributed in body water. Further, we exposed 10 healthy male volunteers to MTBE vapor at 5, 25 and 50 ppm for 2 h during light physical exercise. Uptake and disposition were studied by measuring MTBE and TBA in inhaled and exhaled air, blood and urine. Low uptake, high post-exposure exhalation, and low blood clearance indicate slow metabolism of MTBE relative to many other solvents. A low recovery of TBA in urine (below 1% of uptake) indicates further metabolism of TBA. The concentration of MTBE and TBA in blood was proportional to exposure level suggesting linear kinetics up to 50 ppm. The half life of 7-10 h in blood and urine indicates that TBA would be more suitable than the parent compound as a biomarker for MTBE exposure. Subjective ratings (discomfort, irritative symptoms, CNS effects) and eye (redness, tear film break-up time, conjunctival damage, blinking frequency) and nose (peak expiratory flow, acoustic rhinometry, inflammatory markers in nasal lavage) measurements indicated no or minimal effects of MTBE.

  18. Effective therapeutic approach for head and neck cancer by an engineered minibody targeting the EGFR receptor.

    Young Pil Kim

    Full Text Available Cetuximab, a chimeric monoclonal antibody developed for targeting the Epidermal Growth Factor Receptor (EGFR, has been intensively used to treat cancer patients with metastatic colorectal cancer and head and neck cancer. Intact immunoglobulin G (IgG antibody like cetuximab, however, has some limitations such as high production cost and low penetration rate from vasculature into solid tumor mass due to its large size. In attempt to overcome these limitations, we engineered cetuximab to create single chain variable fragments (scFv-CH3; Minibody that were expressed in bacterial system. Among three engineered minibodies, we found that MI061 minibody, which is composed of the variable heavy (VH and light (VL region joined by an 18-residue peptide linker, displays higher solubility and better extraction properties from bacterial lysate. In addition, we validated that purified MI061 significantly interferes ligand binding to EGFR and blocks EGFR's phosphorylation. By using a protein microarray composed of 16,368 unique human proteins covering around 2,400 plasma membrane associated proteins such as receptors and channels, we also demonstrated that MI061 only recognizes the EGFR but not other proteins as compared with cetuximab. These results indicated that engineered MI061 retains both binding specificity and affinity of cetuximab for EGFR. Although it had relatively short half-life in serum, it was shown to be highly significant anti-tumor effect by inhibiting ERK pathway in A431 xenograft model. Taken together, our present study provides compelling evidence that engineered minibody is more effective and promising agent for in vivo targeting of solid tumors.

  19. The Preclinical and Clinical Effects of Vilazodone for the Treatment of Major Depressive Disorder

    Sahli, Zeyad T.; Banerjee, Pradeep; Tarazi, Frank I.


    ABSTRACT Introduction: Major depressive disorder (MDD) is the leading cause of disability worldwide, and according to the STAR*D trial, only 33% of patients with MDD responded to initial drug therapy. Augmentation of the leading class of antidepressant treatment, selective serotonin reuptake inhibitors (SSRIs), with the 5-HT1A receptor agonist buspirone has been shown to be effective in treating patients that do not respond to initial SSRI therapy. This suggests that newer treatments may improve the clinical picture of MDD. The US Food and Drug Administration (FDA) approved the antidepressant drug vilazodone (EMD 68843), a novel SSRI and 5-HT1A receptor partial agonist. Vilazodone has a half-life between 20–24 hours, reaches peak plasma concentrations at 3.7–5.3 hours, and is primarily metabolized by the hepatic CYP450 3A4 enzyme system. Areas covered: The authors review the preclinical and clinical profile of vilazodone. The roles of serotonin, the 5-HT1A receptor, and current pharmacotherapy approaches for MDD are briefly reviewed. Next, the preclinical pharmacological, behavioral, and physiological effects of vilazodone are presented, followed by the pharmacokinetic properties and metabolism of vilazodone in humans. Last, a brief summary of the main efficacy, safety, and tolerability outcomes of clinical trials of vilazodone is provided. Expert opinion: Vilazodone has shown efficacy versus placebo in improving depression symptoms in several double-blind, placebo-controlled trials. The long-term safety and tolerability of vilazodone treatment has also been established. Further studies are needed that directly compare patients treated with an SSRI (both with and without an adjunctive 5-HT1A partial agonist) versus patients treated with vilaozodone. PMID:26971593

  20. Forbidden nonunique β decays and effective values of weak coupling constants

    Haaranen, M.; Srivastava, P. C.; Suhonen, J.


    Forbidden nonunique β decays feature shape functions that are complicated combinations of different nuclear matrix elements and phase-space factors. Furthermore, they depend in a very nontrivial way on the values of the weak coupling constants, gV for the vector part and gA for the axial-vector part. In this work we include also the usually omitted second-order terms in the shape functions to see their effect on the computed decay half-lives and electron spectra (β spectra). As examples we study the fourth-forbidden nonunique ground-state-to-ground-state β- decay branches of 113Cd and 115In using the microscopic quasiparticle-phonon model and the nuclear shell model. A striking new feature that is reported in this paper is that the calculated shape of the β spectrum is quite sensitive to the values of gV and gA and hence comparison of the calculated with the measured spectrum shape opens a way to determine the values of these coupling constants. This article is designed to show the power of this comparison, coined spectrum-shape method (SSM), by studying the two exemplary β transitions within two different nuclear-structure frameworks. While the SSM seems to confine the gV values close to the canonical value gV=1.0 , the values of gA extracted from the half-life data and by the SSM emerge contradictory in the present calculations. This calls for improved nuclear-structure calculations and more measured data to systematically employ SSM for determination of the effective value of gA in the future.

  1. Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor.

    Neil L Spector

    Full Text Available The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER in human tumors.Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor.In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers.Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor concentrations that maximally

  2. A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics.

    Roberts, Darren M; Liu, Xin; Roberts, Jason A; Nair, Priya; Cole, Louise; Roberts, Michael S; Lipman, Jeffrey; Bellomo, Rinaldo


    Continuous renal replacement therapy (CRRT) may alter antibiotic pharmacokinetics and increase the risk of incorrect dosing. In a nested cohort within a large randomized controlled trial, we assessed the effect of higher (40 mL/kg per hour) and lower (25 mL/kg per hour) intensity CRRT on antibiotic pharmacokinetics. We collected serial blood samples to measure ciprofloxacin, meropenem, piperacillin-tazobactam, and vancomycin levels. We calculated extracorporeal clearance (CL), systemic CL, and volume of distribution (Vd) by non-linear mixed-effects modelling. We assessed the influence of CRRT intensity and other patient factors on antibiotic pharmacokinetics. We studied 24 patients who provided 179 pairs of samples. Extracorporeal CL increased with higher-intensity CRRT but the increase was significant for vancomycin only (mean 28 versus 22 mL/minute; P = 0.0003). At any given prescribed CRRT effluent rate, extracorporeal CL of individual antibiotics varied widely, and the effluent-to-plasma concentration ratio decreased with increasing effluent flow. Overall, systemic CL varied to a greater extent than Vd, particularly for meropenem, piperacillin, and tazobactam, and large intra-individual differences were also observed. CRRT dose did not influence overall (systemic) CL, Vd, or half-life. The proportion of systemic CL due to CRRT varied widely and was high in some cases. In patients receiving CRRT, there is great variability in antibiotic pharmacokinetics, which complicates an empiric approach to dosing and suggests the need for therapeutic drug monitoring. More research is required to investigate the apparent relative decrease in clearance at higher CRRT effluent rates. NCT00221013. Registered 14 September 2005.

  3. Investigation and Optimization of the Effect of Polymers on Drug Release of Norfloxacin from Floating Tablets.

    Gadade, Dipak D; Sarda, Kalpana; Shahi, Sadhana R


    Norfloxacin is fluoroquinolone anti-infective used in the treatment of urinary tract infections, prostatitis, gonorrhea and genital tract infections. It has plasma half life of 3 to 4 h requiring multiple dosing in the treatment. Releaseretarding polymers can be used to modulate the drug release of norfloxacin. The objective of this study was to investigate the effect of release-retarding polymers on the drug release of norfloxacin from floating tablets. Norfloxacin was procured as a gift sample from Concept Pharma Ltd. Aurangabad (India) and HPMC K100M was procured as a gift sample from Colorcon Asia Pvt. Ltd., Goa (India). The tablets were prepared by direct compression method and various pharmaceutical parameters were evaluated. It was observed that all tablet formulations F1-F9 retained the drug release up to 12 h with good floating property but only Batch-F4 complies with the USP dissolution limits with a minimum floating lag time. The drug release kinetics were evaluated by the model-dependent (curve fitting) method using PCP Disso v3 software shows Batch-F4 shows to best fit with Peppas model for which R2 value was 0.9921 and the release exponent value was 0.6892. The drug release kinetics study indicates that the floating tablets release the drug by diffusion followed by erosion mechanism. Obtained in-vitro drug release data was analyzed by design expert software for drug release at first hour and at 12th h values and found that release the selected independent variables like HPMC K100M and sodium alginate concentration has a significant effect on drug release.

  4. Active loading of gemcitabine into liposomes

    Møkleby, Tormund Aasjord


    Gemcitabine is a well established anticancer compound, and is in use today against several types of cancers. Gemcitabine has a short half life. Formulations of gemcitabine containing liposomes could extend it's half life, thereby maybe improving its effectiveness. Also, liposomes in the smaller size range have an advantage when it comes to treating cancer. They accumulate at the site of the tumor, and stay there for a longer time than it would have done in normal tissue(Massing and Fuxius 2...

  5. Investigation of $\\alpha$-decay rates of $^{221}$Fr, $^{224}$Ra and $^{226}$Ra in different environments


    It has recently been suggested, and indicated experimentally, that $\\alpha$- decay half-lives are modified by solid state effects in the surrounding environment. We propose here to measure with high accuracy the $\\alpha$-decay half-life of $^{221}$Fr, $^{224}$Ra and $^{226}$Ra in insulators and metals. Furthermore we plan to investigate the temperature dependency of the half-life in these materials (room temperature, 4 K and 10 mK).

  6. Lack of effect of tenoxicam on glibornuride kinetics and response.

    Stoeckel, K; Trueb, V; Dubach, U C; Heintz, R C; Ascalone, V; Forgo, I.; Hennes, U


    The pharmacokinetics of glibornuride (25 mg i.v.) and the accompanying insulin and glucose responses were characterized in eight human subjects in the presence and absence of steady-state tenoxicam (20 mg p.o./day for 2 weeks). Tenoxicam affected neither the pharmacokinetic parameters of glibornuride (systemic clearance, volume of distribution and biological half-life) nor the responses of plasma insulin and blood glucose to glibornuride. The single i.v. dose of glibornuride had no detectable...

  7. Studies on mRNA electroporation of immature and mature dendritic cells: Effects on their immunogenic potential

    Met, O.; Eriksen, J.; Svane, Inge Marie


    Previous studies have shown that mRNA-electroporated dendritic cells (DCs) are able to process and present tumor-associated antigens, leading to the activation of tumor-specific T cells in vitro and in vivo. However, the optimal maturation state of antigen loading and half-life of the m...

  8. PEGylation of interleukin-10 improves the pharmacokinetic profile and enhances the antifibrotic effectivity in CCl4-induced fibrogenesis in mice

    Mattos Pinto, Adriana; de Jager-Krikken, Alie; de Haan, Marianne; Beljaars, Leonie; Poelstra, Klaas


    Liver fibrosis represents a scar formation process as a response to chronic injury and a major cause of death worldwide. To date, no drug is available for this condition. Interleukin-10 (IL-10) has potent anti-inflammatory and antifibrotic properties but its short half-life in the circulation

  9. PEGylation of interleukin-10 improves the pharmacokinetic profile and enhances the antifibrotic effectivity in CCl4-induced fibrogenesis in mice

    Mattos Pinto, Adriana; de Jager-Krikken, Alie; de Haan, Marianne; Beljaars, Leonie; Poelstra, Klaas


    Liver fibrosis represents a scar formation process as a response to chronic injury and a major cause of death worldwide. To date, no drug is available for this condition. Interleukin-10 (IL-10) has potent anti-inflammatory and antifibrotic properties but its short half-life in the circulation hamper

  10. Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer.

    Guo, Liangran; Fan, Li; Ren, Jinfeng; Pang, Zhiqing; Ren, Yulong; Li, Jingwei; Wen, Ziyi; Qian, Yong; Zhang, Lin; Ma, Hang; Jiang, Xinguo


    The intractability of non-small cell lung cancer (NSCLC) to multimodality treatments plays a large part in its extremely poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cytokine for selective induction of apoptosis in cancer cells; however, many NSCLC cell lines are resistant to TRAIL-induced apoptosis. The therapeutic effect can be restored by treatments combining TRAIL with chemotherapeutic agents. Actinomycin D (ActD) can sensitize NSCLC cells to TRAIL-induced apoptosis by upregulation of death receptor 4 (DR4) or 5 (DR5). However, the use of ActD has significant drawbacks due to the side effects that result from its nonspecific biodistribution in vivo. In addition, the short half-life of TRAIL in serum also limits the antitumor effect of treatments combining TRAIL and ActD. In this study, we designed a combination treatment of long-circulating TRAIL liposomes and ActD liposomes with the aim of resolving these problems. The combination of TRAIL liposomes and ActD liposomes had a synergistic cytotoxic effect against A-549 cells. The mechanism behind this combination treatment includes both increased expression of DR5 and caspase activation. Moreover, systemic administration of the combination of TRAIL liposomes and ActD liposomes suppressed both tumor formation and growth of established subcutaneous NSCLC xenografts in nude mice, inducing apoptosis without causing significant general toxicity. These results provide preclinical proof-of-principle for a novel therapeutic strategy in which TRAIL liposomes are safely combined with ActD liposomes.

  11. Effects of early-life lead exposure on oxidative status and phagocytosis activity in great tits (Parus major).

    Rainio, Miia J; Eeva, Tapio; Lilley, Thomas; Stauffer, Janina; Ruuskanen, Suvi


    Lead is a highly poisonous metal with a very long half-life, distributing throughout the body in blood and accumulating primarily in bones and kidney. We studied the short and long-term effects of early-life lead exposure on antioxidant defense and phagocytosis activity in a small passerine bird, the great tit (Parus major) by manipulating dietary lead levels of the nestlings. We had three experimental groups, exposed to environmentally relevant lead concentrations; high (4 μg/g body mass), low (1 μg/g body mass) and control (0 μg/g body mass) group. As a comparison, a great tit population breeding in the vicinity of a metal smelter was included to the experimental set-up. We measured glutathione, the ratio of reduced and oxidized glutathione, and the antioxidant enzymes: glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase together with protein carbonylation and phagocytosis activity to study the effects of lead on the oxidative status and immune function of birds. We found differences in enzyme activities between the study groups, but in most cases the smelter group differed from the other groups. Despite the differences observed in antioxidant enzymes, our results indicate only minor short-term effects of lead exposure on oxidative status, since either glutathione ratio or protein carbonylation were not affected by lead. Phagocytosis activity was not linked to higher lead concentrations either. Interestingly, protein carbonylation was positively associated with enzyme activities and glutathione level. Our results did not show major long-term effects of lead on the oxidative status of great tits.

  12. Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans.

    Hooker, Jacob M; Xu, Youwen; Schiffer, Wynne; Shea, Colleen; Carter, Pauline; Fowler, Joanna S


    Salvia divinorum, a mint plant originally used by the Mazatecs of Oaxaca, Mexico in spiritual rituals has gained popularity, in smoked form, as a legal hallucinogen in the United States and Europe. Abuse results in rapid onset and short-lasting effects that include visual hallucinations and motor-function impairment. Salvinorin A, the psychoactive component of S. divinorum, is a uniquely potent agonist at kappa-opioid receptors, targets for new therapeutic drugs. We labeled salvinorin A with C-11 by acylation of salvinorin B with [11C]-acetyl chloride to study whether its kinetic behavior in the brain parallels its uniquely fast, yet brief physiological effects. Positron emission tomography (PET) studies performed in 6 adult female baboons indicated extremely rapid brain uptake reaching a peak accounting for 3.3% of the total administered dose in 40 s and clearing with a half-life of 8 min. [11C]-salvinorin A was distributed throughout the brain with the highest concentration in the cerebellum and a notable concentration in the visual cortex, perhaps accounting for its physiological effects when smoked. Naloxone administration did not reduce the overall concentration of [11C]-salvinorin A significantly nor did it change its regional distribution. Peripheral organ kinetics suggested at least two modes of metabolism and excretion occur: through the renal and biliary systems. Our findings have revealed that the exceptionally rapid uptake and brief duration of salvinorin A in the brain match the time-course of visual hallucinations for S. divinorum when smoked. The effects of salvinorin A may occur at <10 mug in the human brain, emphasizing its remarkable potency.

  13. Structure-specific effects of lipidated oxytocin analogs on intracellular calcium levels, parental behavior, and oxytocin concentrations in the plasma and cerebrospinal fluid in mice.

    Cherepanov, Stanislav M; Yokoyama, Shigeru; Mizuno, Akira; Ichinose, Wataru; Lopatina, Olga; Shabalova, Anna A; Salmina, Alla B; Yamamoto, Yasuhiko; Okamoto, Hiroshi; Shuto, Satoshi; Higashida, Haruhiro


    Oxytocin (OT) is a neuroendocrine nonapeptide that plays an important role in social memory and behavior. Nasal administration of OT has been shown to improve trust in healthy humans and social interaction in autistic subjects in some clinical trials. As a central nervous system (CNS) drug, however, OT has two unfavorable characteristics: OT is short-acting and shows poor permeability across the blood-brain barrier, because it exists in charged form in the plasma and has short half-life. To overcome these drawbacks, an analog with long-lasting effects is required. We previously synthesized the analog, lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated to the cysteine and tyrosine residues. In this study, we synthesized and evaluated the analogs lipo-oxytocin-2 (LOT-2) and lipo-oxytocin-3 (LOT-3), which feature the conjugation of one palmitoyl group at the cysteine and tyrosine residues, respectively. In human embryonic kidney-293 cells overexpressing human OT receptors, these three LOTs demonstrated comparably weak effects on the elevation of intracellular free calcium concentrations after OT receptor activation, compared to the effects of OT. The three LOTs and OT exhibited different time-dependent effects on recovery from impaired pup retrieval behavior in sires of CD38-knockout mice. Sires treated with LOT-1 showed the strongest effect, whereas others had no or little effects at 24 h after injection. These results indicated that LOTs have structure-specific agonistic effects, and suggest that lipidation of OT might have therapeutic benefits for social impairment.

  14. To Explore the Effect of Trinity Comprehensive Treatment Including Abdominal Cavity Perfusion Chemotherapy, RF Deep Thermal Therapy and the Immune Therapy in the Treatment of Advanced Ovarian Cancer%腹腔热灌注化疗、体外射频深部热疗、免疫治疗三位一体综合治疗在晚期卵巢癌中的临床应用

    王俊芳; 崔萍; 毛莉; 张延志; 程丽娟


    Objective To evaluate the effect of the trinity comprehensive treatment including the peritoneal cavity hot perfusion chemotherapy, the deep in vitro rf heat therapy and the immune therapy of the treatment for the patients with advanced ovarian cancer.Methods42 cases of patients with advanced epithelial ovarian cancer in our department were selected as the research object. The patients were randomly divided into treatment group and intraperitoneal chemotherapy group. The indicators including the ascites control, KPS score after treatment, CA125 half-life and the incidence of bone marrow suppression were analyzed. Results42 cases of patients had complete 6 courses of chemotherapy. The results of the indicators were: control of ascites (90.9%: 90.9%), KPS score comparison after treatment (31.8%: 60.0%), CA125 half-life (17.3 +/- 5.1 days, 13.4 +/- 4.5 days) and the incidence of bone marrow suppression (18.2%: 40.0%). Conclusion The trinity comprehensive therapy "Hot perfusion chemotherapy combined with abdominal cavity with deep in vitro rf heat therapy, immune therapy" in the treatment of advanced ovarian cancer can signiifcantly improve the ascites control, increase the KPS score, shorten the CA125 half-life and reduce the incidence of bone marrow suppression. This method can improve the body immunity, promote hemopoietic function which is a kind of effective treatment for advanced ovarian cancer. It can improve the survival rate and life quality of advanced ovarian cancer patients.%目的:评价腹腔热灌注化疗联合体外射频深部热疗、免疫治疗三位一体综合治疗在晚期卵巢癌中的临床应用。方法将我科收治晚期上皮性卵巢癌患者42例作为研究对象。将其随机分为综合治疗组和腹腔化疗组。分析两组腹水控制率、治疗后KPS评分、CA125半衰期、骨髓抑制发生率。结果42例病人均完成全部6疗程化疗,两组观察指标分别是:腹水控制率(90.9%:75.0%

  15. An antidote approach to reduce risk and broaden utility of antibody based therapeutics.

    Portnoff, Alyse D; Gao, Cuihua; Borrok, M Jack; Gao, Xizhe; Gao, Changshou; Rainey, G Jonah


    Antibody therapeutics offer safe and effective treatment options for a broad range of diseases. One of the greatest benefits of antibody therapeutics is their extraordinarily long serum half-life, allowing infrequent dosing with long-lasting effects. One characteristic of antibodies that drives long half-life is the ability to interact with the recycling receptor, FcRn, in a pH-dependent manner. The benefit of long half-life, however, carries with it liabilities. While the positive effects of antibody therapeutics are long-lasting, any acute adverse events or chronic negative impacts, such as immunosuppression in the face of an infection, are also long-lasting. Therefore, we sought to develop antibodies with a chemical handle that alone would enjoy the long half-life of normal antibodies, but upon addition of a small-molecule antidote, would interact with the chemical handle and inhibit the antibody recycling mechanism thus leading to rapid degradation and shortened half-life in vivo. Here we present a proof of concept study where we identify sites to incorporate a nnAA that can be chemically modified to modulate FcRn interaction in vitro and antibody half-life in vivo. This is an important first step in developing safer therapeutics, and the next step will be development of technology that can perform the modifying chemistry in vivo.

  16. Effect of PEG-modification on the pharmacokinetics of recombinant human erythropoietin in rats%聚乙二醇修饰对重组人促红细胞生成素在大鼠体内药代动力学的影响

    王诗鸿; 王秀中; 董立厚; 陈方; 宋海峰


    Objective: To determine the effect of PEG-modification on the pharmacokinetics of recombinant human erythropoietin in rats. Methods: Eighteen rats were equally randomized into three groups. EPO, M-PEG-EPO and G-PEG-EPO at 5 μg·kg were subcutaneously injected, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the plasma concentrations of EPO, M-PEG-EPO and G-PEG-EPO. Results: After administration, the Tmax of M-PEG-EPO and G-PEG-EPO was later than that of EPO. The peak concentrations of M-PEG-EPO and G-PEG-EPO in plasma were lower than that of EPO. M-PEG-EPO and G-PEG-EPO were cleared slower as the terminal half-life was prolonged relatively. There was no statistically significant difference between M-PEG-EPO and G-PEG-EPO in pharmacokinetics parameters except AUC0-inf and Cls. Conclusion: PEG-modification of EPO can prolong the terminal half-life of EPO in rats. The pharmacokinetics of M-PEG-EPO and G-PEG-EPO in rats is similar.%目的:研究聚乙二醇修饰对重组人促红细胞生成素在大鼠体内药代动力学的影响.方法:大鼠随机分成3组,分别单次皮下注射5 μg· kg-1氨基葡萄糖-聚乙二醇-EPO(G-PEG-EPO)、甲氧基-聚乙二醇-EPO(M-PEG-EPO)和未经修饰的EPO原液后采集血样,采用酶联免疫吸附分析(ELISA)测定大鼠血浆样品中的EPO浓度.结果:给药后,与EPO相比,M-PEG-EPO,G-PEG-EPO较EPO吸收过程缓慢,峰浓度Cmax水平显著降低,代谢清除相对缓慢,末端消除相半衰期t1/2明显延长.而M-PEG-EPO,G-PEG-EPO的药代动力学参数除AUC0-inf和Cls外均无统计学差异.结论:聚乙二醇修饰能显著延长EPO在大鼠的末端消除相半衰期,G-PEG-EPO和M-PEG-EPO在大鼠的药代动力学性质相似.

  17. A phase-3, double-blind, placebo-controlled study of the effectiveness and safety of single oral doses of secnidazole 2 g for the treatment of women with bacterial vaginosis.

    Schwebke, Jane R; Morgan, Franklin G; Koltun, William; Nyirjesy, Paul


    A novel single oral dose granule formulation of secnidazole 2 g, a 5-nitroimidazole with a longer half-life (∼17 hours) than metronidazole (∼8 hours), is being developed to treat bacterial vaginosis. We sought to evaluate the effectiveness and safety of single-dose secnidazole 2 g compared to placebo for the treatment of women with bacterial vaginosis. In all, 189 women with bacterial vaginosis were randomized 2:1 to receive a single oral dose of secnidazole 2 g (N = 125) or matched placebo (N = 64) at 21 centers in the United States. The primary endpoint was the proportion of clinical outcome responders, defined as those with: (1) normal vaginal discharge; (2) negative 10% potassium hydroxide whiff test; and (3) vaginosis after treatment; (2) negative potassium hydroxide whiff tests; and (3) clue cells vaginosis, were consistent with the clinical outcome responder rate analysis (58.9% vs 24.6%; P vaginosis treatment (68.0% [68/100] vs 29.6% [16/54]; P vaginosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Efeito da luz e da temperatura de congelamento sobre a estabilidade das antocianinas da pitanga roxa The effects of light and freezing temperature upon the stability of purple surinam cherry's anthocyanins

    Vera Lúcia Arroxelas G. de Lima


    Full Text Available As antocianinas são corantes naturais que podem ser utilizadas como alternativa em substituição aos corantes sintéticos. Entretanto, a baixa estabilidade destes compostos é o principal fator que dificulta sua aplicação como corante em alimentos. Frente à escassez de estudo sobre o pigmentos antociânicos da pitanga roxa, este trabalho teve como propósito avaliar a sua estabilidade à luz e ao congelamento. Utilizando a leitura de absorbância do extrato antociânico submetido às condições experimentais foi evidenciado que a luz reduziu o seu tempo de meia-vida, enquanto que a temperatura de congelamento exerceu pequeno efeito na degradação dos pigmentos.Anthocyanins are natural colorants that can be used as alternative to synthetic dyes. However, the low stability of these compounds is the main drawback in their application as food colorants. Since the information on anthocyanin pigments in Surinam cherry is scarce, the purpose of this investigation was to assess their stability to light and freezing storage. The anthocyanin extract absorbance, under the experimental conditions, showed that light incidence reduced the half-life of anthocyanin extract; meanwhile the freezing storage had little effect on these pigments degradation.

  19. Use of a tantalum-178 generator and a multiwire gamma camera to study the effect of the Mueller maneuver on left ventricular performance: comparison to hemodynamics and single photon emission computed tomography perfusion patterns.

    Gioia, G; Lin, B; Katz, R; DiMarino, A J; Ogilby, J D; Cassel, D; DePace, N L; Heo, J; Iskandrian, A S


    During the Mueller maneuver, there is a decrease in intrathoracic pressure and an increase in transmural left ventricular pressure. The changes in loading conditions cause transient left ventricular dysfunction. This study examined the effects of the Mueller maneuver on left ventricular performance using tantalum (Ta)-178 (half-life 9.3 min) and a multiwire gamma camera. First-pass radionuclide angiograms were obtained at baseline and during Mueller maneuver in 41 patients aged 58 +/- 10 years. In 34 patients, stress single photon emission computed tomography (SPECT) myocardial perfusion imaging with thallium-201 or sestamibi was also performed. Hemodynamic measurements during the Mueller maneuver (n = 10) showed a decrease in systemic pressure (139 +/- 25 mm Hg vs 123 +/- 24 mm Hg, p or = 5%) in 17 patients (group 2) (55% +/- 13% vs 40% +/- 16%, p = 0.001). The stress SPECT images showed no or only fixed defects in 11 (65%) patients in group 1 and 3 (18%) patients in group 2 (p = 0.02), and reversible defects in 6 (35%) patients in group 1 and 14 (82%) patients in group 2 (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Inactivating effects of lignin-derived compounds released during lignocellulosic biomass pretreatment on the endo-glucanase catalyzed hydrolysis of carboxymethylcellulose: A study in continuous stirred ultrafiltration-membrane reactor.

    Cantarella, Maria; Mucciante, Claudia; Cantarella, Laura


    This study focusses on the reversible/irreversible damage that selected phenolic compounds, released during steam-explosion pretreatment, mandatory for cellulose accessibility, causes on both stability and activity of a commercial cellulase (half-life=173h) during carboxymethyl-cellulose hydrolysis. Long-term experiments performed in continuous stirred UF-membrane bioreactors, operating at steady-state regime, in controlled operational conditions, allowed evaluating the inactivation-constant in the phenol presence (kd1) and after its removal (kd2) from the reactor feed. p-Hydroxybenzoic acid (1 and 2g L(-1)) are the extreme limits in the inactivating effect with enzyme half-lives 99.02 and 14.15h, respectively. The inactivation reversibility was assessed for vanillic acid, p-hydroxybenzoic acid, syringaldehyde, p-coumaric acid, being kd1>kd2. p-Hydroxybenzaldehyde and protocatechuic acid irreversibly affected cellulase stability increasing its inactivation with kd2>kd1. p-Hydroxybenzaldehyde, 1g L(-1), syringaldehyde, and vanillin, at 2gL(-1), had similar kd1÷kd2.

  1. Antihyperalgesic effect of the GABA(A) ligand clobazam in a neuropathic pain model in mice: a pharmacokinetic-pharmacodynamic study.

    Besson, Marie; Daali, Youssef; Di Lio, Alessandra; Dayer, Pierre; Zeilhofer, Hanns Ulrich; Desmeules, Jules


    Facilitation of spinal GABAergic inhibition with benzodiazepines (BZDs) reverses pain sensitization in animals; however, the use of BZDs in man is limited by their sedative effect. The antihyperalgesic effects of GABA(A) agonists are mediated by GABA(A) receptors containing α2 subunits, whereas sedation is linked to α1 subunit-containing receptors. α2 and α3 selective GABA(A) receptor modulators have been tested in animals but are not yet available for use in human beings. Clobazam is a 1,5-BZD, which exhibits less cognitive side effects than other benzodiazepines. Here, we studied its antihyperalgesic effects in a mouse model of neuropathic pain. Clobazam showed a dose-dependent antihyperalgesic effect in the chronic constriction injury (CCI) model of neuropathic pain, peaking at 1 hr after administration and lasting for 4 hr with no relevant sedation at a dose of 3 mg/kg. At higher doses, the antihyperalgesic effect was stronger, but sedation became significant. The blood and brain kinetics of clobazam were linear over the range of doses tested with a short half-life of the parent compound and a ready penetration of the blood-brain barrier. Clobazam blood concentrations decreased rapidly, falling below the limit of detection at 120 min. after drug application. Its main metabolite, N-desmethyl-clobazam, showed more delayed and prolonged pharmacokinetics, partly explaining why antihyperalgesia persisted when clobazam was no longer detectable in the blood. Considering its therapeutic margin and its pharmacokinetic properties, clobazam would be a valuable compound to assess the role of the GABAergic pathway in pain transmission in human beings.

  2. Neural effects of gut- and brain-derived glucagon-like peptide-1 and its receptor agonist.

    Katsurada, Kenichi; Yada, Toshihiko


    Glucagon-like peptide-1 (GLP-1) is derived from both the enteroendocrine L cells and preproglucagon-expressing neurons in the nucleus tractus solitarius (NTS) of the brain stem. As GLP-1 is cleaved by dipeptidyl peptidase-4 yielding a half-life of less than 2 min, it is plausible that the gut-derived GLP-1, released postprandially, exerts its effects on the brain mainly by interacting with vagal afferent neurons located at the intestinal or hepatic portal area. GLP-1 neurons in the NTS widely project in the central nervous system and act as a neurotransmitter. One of the physiological roles of brain-derived GLP-1 is restriction of feeding. GLP-1 receptor agonists have recently been used to treat type 2 diabetic patients, and have been shown to exhibit pleiotropic effects beyond incretin action, which involve brain functions. GLP-1 receptor agonist administered in the periphery is stable because of its resistance to dipeptidyl peptidase-4, and is highly likely to act on the brain by passing through the blood-brain barrier (BBB), as well as interacting with vagal afferent nerves. Central actions of GLP-1 have various roles including regulation of feeding, weight, glucose and lipid metabolism, cardiovascular functions, cognitive functions, and stress and emotional responses. In the present review, we focus on the source of GLP-1 and the pathway by which peripheral GLP-1 informs the brain, and then discuss recent findings on the central effects of GLP-1 and GLP-1 receptor agonists.

  3. Effects of dietary paraffin, squalane and sucrose polyester on residue disposition and elimination of hexachlorobenzene in rats.

    Richter, E; Fichtl, B; Schäfer, S G


    Previous studies have shown addition of light liquid paraffin to enhance the elimination of organochlorine xenobiotics. In the present study the effect of paraffin on the elimination of [14C]hexachlorobenzene (HCB) was compared with the effect of possible alternative compounds, squalane and sucrose polyester (SPE). Four groups of 7 rats were fed a diet containing 1.5 ppm [14C]HCB for 4 days followed by 10 days on HCB-free diet. Thereafter one group (control) remained on this diet whereas the other 3 groups received a diet supplemented with 8% (w/w) paraffin, squalane or SPE, respectively. Radioactivity in urine and faeces was measured daily and at the end of the experiment in samples of abdominal fat, muscle, liver, kidney and blood. Dietary treatment with either paraffin, squalane or SPE markedly enhanced faecal excretion of [14C]HCB, whereas urinary excretion was not affected. Both the time course as well as the extent of faecal [14C]HCB elimination were similar in the treated groups. After 3 weeks of treatment the amount of [14C]HCB excreted with faeces was about three times higher in treated animals than in controls. The half-life (t1/2) of [14C]HCB elimination from the body was markedly decreased in treated animals (mean 34--38 days) compared to controls (110 days). [14C]HCB concentrations in some major tissues were significantly reduced to the same extent by all three dietary regimens. Thus squalane and SPE are as effective as paraffin in removing HCB from contaminated animals.


    Kuczenski, Ronald; Segal, David S.; Melega, William P.; Lacan, Goran; McCunney, Stanley J.


    Bingeing is one pattern of high dose methamphetamine (METH) abuse which involves continuous drug taking over several days and can result in psychotic behaviors for which the brain pathology remains poorly-defined. A corresponding animal model of this type of METH exposure may provide novel insights into the neurochemical and behavioral sequelae associated with this condition. Accordingly, to simulate the pharmacokinetic profile of a human METH binge exposure in rats we used a computer-controlled, intravenous METH procedure (dynamic infusion) to overcome species differences in METH pharmacokinetics and to replicate the human 12-h plasma METH half-life. Animals were treated over 13 weeks with escalating METH doses, using dynamic infusion, and then exposed to a binge in which drug was administered every 3 h for 72h. Throughout the binge, behavioral effects included unabated intense oral stereotypies in the absence of locomotion and in the absence of sleep. Decrements in regional brain dopamine, norepinephrine and serotonin levels, measured at 1 and 10 h after the last injection of the binge, had, with the exception of caudate-putamen dopamine and frontal cortex serotonin, recovered by 48 h. At 10 h after the last injection of the binge, [3H]ligand binding to dopamine and vesicular monoamine transporters in caudate-putamen were reduced by 35% and 13%, respectively. In a separate METH binge treated cohort, post-binge behavioral alterations were apparent in an attenuated locomotor response to a METH challenge infusion at 24h after the last injection of the binge. Collectively, the changes we characterized during and following a METH binge suggest that for humans under similar exposure conditions, multiple time-dependent neurochemical deficits contribute to their behavioral profiles. PMID:19571794

  5. Human methamphetamine pharmacokinetics simulated in the rat: behavioral and neurochemical effects of a 72-h binge.

    Kuczenski, Ronald; Segal, David S; Melega, William P; Lacan, Goran; McCunney, Stanley J


    Bingeing is one pattern of high-dose methamphetamine (METH) abuse, which involves continuous drug taking over several days and can result in psychotic behaviors for which the brain pathology remains poorly defined. A corresponding animal model of this type of METH exposure may provide novel insights into the neurochemical and behavioral sequelae associated with this condition. Accordingly, to simulate the pharmacokinetic profile of a human METH binge exposure in rats, we used a computer-controlled, intravenous METH procedure (dynamic infusion, DI) to overcome species differences in METH pharmacokinetics and to replicate the human 12-h plasma METH half-life. Animals were treated over 13 weeks with escalating METH doses, using DI, and then exposed to a binge in which drug was administered every 3 h for 72 h. Throughout the binge, behavioral effects included unabated intense oral stereotypies in the absence of locomotion and in the absence of sleep. Decrements in regional brain dopamine, norepinephrine, and serotonin levels, measured at 1 and 10 h after the last injection of the binge, had, with the exception of caudate-putamen dopamine and frontal cortex serotonin, recovered by 48 h. At 10 h after the last injection of the binge, [(3)H]ligand binding to dopamine and vesicular monoamine transporters in caudate-putamen were reduced by 35 and 13%, respectively. In a separate METH binge-treated cohort, post-binge behavioral alterations were apparent in an attenuated locomotor response to a METH challenge infusion at 24 h after the last injection of the binge. Collectively, the changes we characterized during and after a METH binge suggest that for human beings under similar exposure conditions, multiple time-dependent neurochemical deficits contribute to their behavioral profiles.

  6. Effects of hepatic dysfunction on the single-dose pharmacokinetics of fesoterodine.

    de Mey, Christian; Mateva, Lyudmila; Krastev, Zahariy; Sachse, Richard; Wood, Nolan; Malhotra, Bimal


    Fesoterodine, a new antimuscarinic for the treatment of overactive bladder, is rapidly and extensively hydrolyzed by nonspecific esterases to its principal active moiety, 5-hydroxymethyl tolterodine (5-HMT). The elimination of 5-HMT involves metabolism and renal excretion. The plasma and urinary pharmacokinetics of 5-HMT and its inactive carboxy (SPM 5509), N-desisopropyl (SPM 7789), and carboxy-N-desisopropyl (SPM 7790) metabolites were investigated after a single oral dose of 8 mg of fesoterodine in 8 male subjects with moderate hepatic cirrhosis (Child-Turcotte-Pugh class B) and 8 matched healthy controls. The estimated mean ratios (95% confidence interval) of the area under the curve extrapolated to infinity after dosing (AUC(0-∞)), cumulative urinary excretion up to 48 hours after dosing (Ae(0-48)), maximum observed concentration (C(max)), and apparent terminal disposition half-life (t(1/2)) of 5-HMT for cirrhotic and healthy subjects were 2.2 (1.5-3.1), 2.5 (1.7-3.8), 1.4 (1.0-1.9), and 1.1 (0.8-1.3), respectively. In subjects with hepatic cirrhosis, AUC(0-∞) and Ae(0-48) of 5-HMT increased approximately 2-fold; the increase in C(max) was smaller, and t(1/2) was unaffected. AUC and C(max) of the inactive carboxy metabolites, SPM 5509 and SPM 7790, were reduced reciprocally by about 50%, whereas exposure to the dealkylated metabolite, SPM 7789, increased about 2-fold. Fesoterodine 8 mg was equally well tolerated in both groups. The results indicate that moderate hepatic cirrhosis reduces 5-HMT clearance, with an apparent effect on the carboxylation pathway and not on dealkylation.

  7. Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns.

    Šíma, M; Pokorná, P; Hronová, K; Slanař, O


    Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic-ischemic encephalopathy. The objective of our study was to describe possible effect of frequently co-administered medications (dopamine, dobutamine, norepinephrine, furosemide, phenytoin, and analgesics) on the phenobarbital pharmacokinetics in full term newborns with hypoxic-ischemic encephalopathy. Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non-compartmental analysis. Co-medication was evaluated throughout the whole treatment period up to 5 days. Volume of distribution, clearance, and half-life median values (95 % CI) for phenobarbital in the whole study population (n=37) were 0.48 (0.41-0.56) l/kg, 0.0034 (0.0028-0.0040) l/h/kg, and 93.7 (88.1-99.2) h, respectively. Phenobarbital pharmacokinetic parameters were not significantly affected by vasoactive drugs (dopamine, dobutamine, and norepinephrine), furosemide, phenytoin, or analgesics. Furthermore, no dose-dependent alteration of phenobarbital pharmacokinetic parameters was noted for vasoactive medication at doses equivalent to cumulative vasoactive-inotropic score (area under the curve in a plot of vasoactive-inotropic score against time) 143.2-8473.6, furosemide at cumulative doses of 0.2-42.9 mg/kg, or phenytoin at cumulative doses of 10.3-46.2 mg/kg. Phenobarbital pharmacokinetics was not affected by investigated co-administered drugs used in newborns with hypoxic-ischemic encephalopathy in real clinical settings.

  8. The effect of itraconazole on the pharmacokinetics and pharmacodynamics of bromazepam in healthy volunteers.

    Oda, Manami; Kotegawa, Tsutomu; Tsutsumi, Kimiko; Ohtani, Yasukiyo; Kuwatani, Keiji; Nakano, Shigeyuki


    Bromazepam, an anti-anxiety agent, has been reported to be metabolized by cytochrome P(450) (CYP). However, the enzyme responsible for the metabolism of bromazepam has yet to be determined. The purpose of this study was to examine whether the inhibition of CYP3A4 produced by itraconazole alters the pharmacokinetics and pharmacodynamics of bromazepam. Eight healthy male volunteers participated in this randomized double-blind crossover study. The subjects received a 6-day treatment of itraconazole (200 mg daily) or its placebo. On day 4 of the treatment, each subject received a single oral dose of bromazepam (3 mg). Blood samplings for drug assay were performed up to 70 h after bromazepam administration. The time course of the pharmacodynamic effects of bromazepam on the central nervous system was assessed using a subjective rating of sedation, continuous number addition test and electroencephalography up to 21.5 h after bromazepam administration. Itraconazole caused no significant changes in the pharmacokinetics and pharmacodynamics of bromazepam. The mean (+/-SD) values of area under the plasma concentration-time curve and elimination half-life for placebo versus itraconazole were 1328+/-330 ng h/ml versus 1445+/-419 ng h/ml and 32.1+/-9.3 h versus 31.1+/-8.4 h, respectively. The pharmacokinetics and pharmacodynamics of bromazepam were not affected by itraconazole, suggesting that CYP3A4 is not involved in the metabolism of bromazepam to a major extent. It is likely that bromazepam can be used in the usual doses for patients receiving itraconazole or other CYP3A4 inhibitors.

  9. Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles

    Cai LL


    Full Text Available Lulu Cai,1,* Neng Qiu,2,* Mingli Xiang,3,* Rongsheng Tong,1 Junfeng Yan,1 Lin He,1 Jianyou Shi,1 Tao Chen,4 Jiaolin Wen,3 Wenwen Wang,3 Lijuan Chen31Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, 2College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, 3State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China; 4Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada *These authors contributed equally to this paperAbstract: The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa methoxy poly(ethylene glycol methyl ether (mPEG to gambogic acid (GA-mPEG2000 through an ester linkage and characterized by 1H nuclear magnetic resonance. The GA-mPEG2000 conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG2000 micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide tests demonstrated that the GA-mPEG2000 micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG2000 micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG2000 micelles may have promising applications in tumor therapy.Keywords: gambogic acid, poly(ethylene glycol-drug conjugate, micelle, antitumor, toxicity

  10. TRIP12 as a mediator of human papillomavirus/p16-related radiation enhancement effects.

    Wang, L; Zhang, P; Molkentine, D P; Chen, C; Molkentine, J M; Piao, H; Raju, U; Zhang, J; Valdecanas, D R; Tailor, R C; Thames, H D; Buchholz, T A; Chen, J; Ma, L; Mason, K A; Ang, K-K; Meyn, R E; Skinner, H D


    Patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) have better responses to radiotherapy and higher overall survival rates than do patients with HPV-negative HNSCC, but the mechanisms underlying this phenomenon are unknown. p16 is used as a surrogate marker for HPV infection. Our goal was to examine the role of p16 in HPV-related favorable treatment outcomes and to investigate the mechanisms by which p16 may regulate radiosensitivity. HNSCC cells and xenografts (HPV/p16-positive and -negative) were used. p16-overexpressing and small hairpin RNA-knockdown cells were generated, and the effect of p16 on radiosensitivity was determined by clonogenic cell survival and tumor growth delay assays. DNA double-strand breaks (DSBs) were assessed by immunofluorescence analysis of 53BP1 foci; DSB levels were determined by neutral comet assay; western blotting was used to evaluate protein changes; changes in protein half-life were tested with a cycloheximide assay; gene expression was examined by real-time polymerase chain reaction; and data from The Cancer Genome Atlas HNSCC project were analyzed. p16 overexpression led to downregulation of TRIP12, which in turn led to increased RNF168 levels, repressed DNA damage repair (DDR), increased 53BP1 foci and enhanced radioresponsiveness. Inhibition of TRIP12 expression further led to radiosensitization, and overexpression of TRIP12 was associated with poor survival in patients with HPV-positive HNSCC. These findings reveal that p16 participates in radiosensitization through influencing DDR and support the rationale of blocking TRIP12 to improve radiotherapy outcomes.

  11. Study of seed layer effect in nuclear battery with P-N diode junction

    Uhm, Young Rang; Son, Kwang Jae; Lee, Jun Sig [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Choi, Byoung Gun [Kookmin Univ., Seoul (Korea, Republic of)


    A nuclear battery with diode junction is a device that converts nuclear radiation directly to electric power. The mechanism of a nuclear battery is same as the P-N junction diode for solar cell application. The photovoltaic is operated by converted photons to electrical energy in the junction. In betavoltaic battery, beta particles are collected and converted to electrical energy as similar principle as photovoltaic. A very low current, order of nano or micro amps, is generated in devices. If a radioisotope (RI) with a long halflife (over 50 years) is used, a lifetime of a power source is extended as long as halflife time of RI.. Some special applications require long-lived compact power sources. These include space equipment, sensors in remote locations (space, underground, etc.), and implantable medical devices. Conventionally, these sources rely on converting chemical energy to electricity. This means they require a large storage of chemical 'fuel' since the amount of energy released per reaction is small. The nuclear battery is a novel solution to solve the power needs of these applications. For the {sup 63}Ni beta-source we used, the half-life is 100.2 years. Hence, the power sources we describe could extend a system's operating life by several decades or even a century, during which time the system could gain learned behavior without worrying about the power turning off. Radioactive thin-film-based power sources also have energy density orders of magnitude higher than chemical-reaction-based energy sources. In this study, we fabricate nuclear battery using {sup 63}Ni source with diode junction, and studied seed layer effect for optimization of structure of p-n junction.

  12. Interaction effects of lead on bioavailability and pharmacokinetics of arsenic in the rat.

    Diacomanolis, Violet; Noller, Barry N; Ng, Jack C


    Arsenic (As) and lead (Pb) are common contaminants found in mine waste materials. For an evidence-based risk assessment, it is important to better understand the potential interaction of mixed contaminants; and this interaction study was investigated in an in vivo rat model. Following co-administration of a fixed dose of As(V) as in sodium arsenate and different doses of Pb as lead acetate to Sprague-Dawley rats, blood arsenic concentration and bioavailability decreased. A decrease in As blood concentration when lead was co-administered was observed with increasing lead doses. Pharmacokinetic parameters for As in the blood showed faster absorption and elimination of this metalloid in the presence of Pb. The elimination half-life of As decreased from 67 days in As solo group to 27-30 with doses of Pb. Bioavailability of As was also decreased by 30-43 % in the presence of Pb. Decreased urinary excretion of Pb and tissue accumulation were also observed. It indicates lower absorption of As when co-administered with Pb. A probable explanation for these findings is that As co-administration with Pb could have resulted in the formation of less soluble lead arsenate. However, such an interaction between As and Pb could only explain about one-third of the variation when real mine waste materials containing both of these elements were administered to rats. This suggests that other effects from physical and chemical parameters could contribute to the bioavailability of arsenic in complex real environmental samples.

  13. Epoetin beta pegol, but not recombinant erythropoietin, retains its hematopoietic effect in vivo in the presence of the sialic acid-metabolizing enzyme sialidase.

    Aizawa, Ken; Kawasaki, Ryohei; Tashiro, Yoshihito; Hirata, Michinori; Endo, Koichi; Shimonaka, Yasushi


    Erythropoiesis-stimulating agents (ESAs) are widely used for treating chronic kidney disease (CKD)-associated anemia. The biological activity of ESAs is mainly regulated by the number of sialic acid-containing carbohydrates on the erythropoietin (EPO) peptide. Sialidase, a sialic acid-metabolizing enzyme that accumulates in CKD patients, is suspected of contributing to shortening the circulation half-life of ESAs. Epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.), is an EPO integrated with methoxypolyethylene glycol (PEG). It has been suggested that C.E.R.A. may exert a favorable therapeutic effect, even under conditions of elevated sialidase; however, no detailed investigation of the pharmacological profile of C.E.R.A. in the presence of sialidase has been reported. In the present study, we injected C.E.R.A. or EPO pre-incubated with sialidase into rats, and assessed the hematopoietic effect by reticulocyte count. The hematopoietic effect of C.E.R.A., but not EPO, was preserved after sialidase treatment, despite the removal of sialic acid. Proliferation of EPO-dependent leukemia cells (AS-E2) was significantly increased by desialylated C.E.R.A. and EPO compared to non-treated C.E.R.A. or EPO. In conclusion, we show that C.E.R.A. exerts a favorable hematopoietic effect even under conditions of elevated sialidase. Our findings may contribute to a better understanding of CKD and more effective therapeutic approaches based on a patient's profile of anemia.

  14. Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

    Jiang Wenqi


    Full Text Available Abstract Background It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU loaded block copolymers, with poly(γ-benzyl-L-glutamate (PBLG as the hydrophobic block and poly(ethylene glycol (PEG as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. Methods 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM and transmission electron microscopy (TEM were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC. To study in vivo effects, LoVo cells (human colon cancer cell line or Tca8113 cells (human oral squamous cell carcinoma cell line were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. Results 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min, lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L, and greater distribution volume (VD, 0.114 L vs. 0.069 L. Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p 0.05. Conclusion In our model system, 5-FU/PEG-PBLG nanoparticles

  15. Neutronic effects on tungsten-186 double neutron capture

    Garland, Marc Alan

    Rhenium-188, a daughter product of tungsten-188, is an isotope of great interest in therapeutic nuclear medicine, being used in dozens of laboratory and clinical investigations worldwide. Applications include various cancer therapy strategies, treatment of rheumatoid arthritis, prevention of restenosis following coronary artery angioplasty, and palliation of bone pain associated with cancer metastases. With its half-life of 17 hours, 2.12 MeV (maximum) beta-particle emission, chemical similarity to technetium-99m (the most widely used diagnostic radioisotope), and its availability in a convenient tungsten-188/rhenium-188 generator system, rhenium-188 is a superb candidate for a broad range of applications. Production of 188W is typically via double neutron capture by 186W in a high flux nuclear reactor, predominantly the High Flux Isotope Reactor at the Oak Ridge National Laboratory in Tennessee. Experience at HFIR has shown that production yields (measured in Ci of 188W produced per g of 186W target) decrease considerably as target size increases. While the phenomenon of neutron resonance self-shielding would be expected to produce such an effect, temperature effects on neutron flux distribution and neutron capture rates may also be involved. Experimental investigations of these phenomena have not been previously performed. The work presented in this thesis evaluates the factors that contribute to the decrease in 188W yield from both theoretical and experimental standpoints. Neutron self-shielding and temperature effects were characterized to develop a strategy for target design that would optimize production yield, an important factor in minimizing health care costs. It was determined that decrease in yield due to neutron self-shielding can be attributed to depletion of epithermal neutrons at resonant energies, most significantly within the initial 0.4 mm depth of the target. The results from these studies further show that 188W yield in the interior of the

  16. Systematics of half-lives for proton radioactivity

    Medeiros, E.L.; Rodrigues, M.M.N.; Duarte, S.B.; Tavares, O.A.P. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)]. E-mails:;;


    Half-life measurements for both ground-state and isomeric transitions in proton radioactivity are systematized by using a semiempirical, one-parameter model based on tunneling through a potential barrier, where the centrifugal and overlapping effects are taken into account within the spherical nucleus approximation. This approach, which has been successfully applied to alpha decay cases covering {approx} 30 orders of magnitude in half-life, has shown, in addition, very adequate at fitting all existing data on partial half-life, T{sub 1/2p}, of proton emission from nuclei. Nearly 70 measured half-life values have been analysed, and the data could be described by two straight lines relating the pure Coulomb contribution to half life with the quantity Z{sub d}({mu}{sub 0}/Q{sub p}){sub 1/2} (Z{sub d} is the atomic number of the daughter nucleus, {mu}{sub 0} is the reduced mass, and Q{sub p} is the total nuclear energy available for decay). These straight lines are shown to correspond to different degrees of deformation, namely, very prolate ({delta}> approx. 0.1), and other shaped (delta < approx. 0.1) parent nuclei. The goodness in reproducing the data attained in the present systematics allows for half-life predictions for a few possible cases of proton radioactivity not yet experimentally accessed. (author)

  17. A novel phthalimide derivative, TC11, has preclinical effects on high-risk myeloma cells and osteoclasts.

    Maiko Matsushita

    Full Text Available Despite the recent advances in the treatment of multiple myeloma (MM, MM patients with high-risk cytogenetic changes such as t(4;14 translocation or deletion of chromosome 17 still have extremely poor prognoses. With the goal of helping these high-risk MM patients, we previously developed a novel phthalimide derivative, TC11. Here we report the further characterization of TC11 including anti-myeloma effects in vitro and in vivo, a pharmacokinetic study in mice, and anti-osteoclastogenic activity. Intraperitoneal injections of TC11 significantly delayed the growth of subcutaneous tumors in human myeloma-bearing SCID mice. Immunohistochemical analyses showed that TC11 induced apoptosis of MM cells in vivo. In the pharmacokinetic analyses, the Cmax was 2.1 μM at 1 h after the injection of TC11, with 1.2 h as the half-life. TC11 significantly inhibited the differentiation and function of tartrate-resistant acid phosphatase (TRAP-positive multinucleated osteoclasts in mouse osteoclast cultures using M-CSF and RANKL. We also revealed that TC11 induced the apoptosis of myeloma cells accompanied by α-tubulin fragmentation. In addition, TC11 and lenalidomide, another phthalimide derivative, directly bound to nucleophosmin 1 (NPM1, whose role in MM is unknown. Thus, through multiple molecular interactions, TC11 is a potentially effective drug for high-risk MM patients with bone lesions. The present results suggest the possibility of the further development of novel thalidomide derivatives by drug designing.

  18. Effects of dietary squid viscera meal on growth and cadmium accumulation in tissues of large yellow croaker, Pseudosciaena crocea R.

    Huitao LI; Kangsen MAI; Qinghui AI; Chunxiao ZHANG; Lu ZHANG


    Cadmium (Cd) is a toxic environmental pollutant with a long biological half-life and can produce both hepatic and renal injuries in mammals and fish. Squid viscera meal (SVM), an effective attractant for aquatic animals, is widely used as an ingredient in aquafeeds. However, SVM is rich in Cd and its complexes. A study was conducted to evaluate the effects of dietary SVM on the growth and Cd deposition in the tissues of large yellow croaker, Pseudosciaena crocea R. Three practical diets diet, correspondingly containing a 0.21, 7.26 and 12.08 mg groups of 100 juveniles of large yellow croaker (mean initial weight, 9.75 + 0.35 g) in floating sea cages (1.0 m × 1.0m × 1.5 m). Fish were fed twice daily (05:00 and 17:00) to satiation for 8 weeks. The results showed that there were no significant differences in fish survival among the three dietary treatments, but significant higher specific growth rates (SGR) were observed in the fish fed diets with (P< 0.05). The cadmium concentrations in fish tissues (muscle, liver, kidney and gill) were significantly influ-enced by the dietary SVM. The cadmium concentrations in all tissues significantly increased with increasing dietary Cd levels (P < 0.05). In all the dietary treatments, the high-est Cd level was always observed in the kidney, followed SVM had significantly higher Cd accumulations in the level in fish muscle, however, was undetectable in all treatments. Therefore, based on these results, accumulation of Cd in edible tissue (muscle) of farmed large yellow croaker is not a food safety issue. However, long-term feeding of diets with SVM may result in accumulation of Cd in the kidney, liver and gills of fish.


    Maria Silvia eGiretti


    Full Text Available Estetrol (E4 is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17β-estradiol (E2 on T47-D estrogen receptor (ER positive breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, redistribution of actin fibers towards the cell membrane was observed. However, when E4 was added to E2, a inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin (ERM family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr558, which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of ERα. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring estrogen receptor modulator in the breast.

  20. Effects of light shading and climatic conditions on the metabolic behavior of flonicamid in red bell pepper.

    Jung, Da-I; Farha, Waziha; Abd El-Aty, A M; Kim, Sung-Woo; Rahman, Md Musfiqur; Choi, Jeong-Heui; Kabir, Md Humayun; Im, So Jeong; Lee, Young-Jun; Truong, Lieu T B; Shin, Ho-Chul; Im, Geon-Jae; Shim, Jae-Han


    The degradation behavior of flonicamid and its metabolites (4-trifluoromethylnicotinic acid (TFNA) and N-(4-trifluoromethylnicotinoyl) glycine (TFNG)) was evaluated in red bell pepper over a period of 90 days under glass house conditions, including high temperature, low and high humidity, and in a vinyl house covered with high density polyethylene light shade covering film (35 and 75%). Flonicamid (10% active ingredient) was applied (via foliar application) to all fruits, including those groups grown under normal conditions (glass house) or under no shade cover (vinyl house). Samples were extracted using a Quick, Easy, Cheap, Effective, Rugged, and Safe "QuEChERS" method and analyzed using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The method performance, including linearity, recovery, limits of detection (LOD), and quantitation (LOQ), was satisfactory. Throughout the experimental period, the residual levels of flonicamid and TFNG were not uniform, whereas that of TFNA remained constant. The total sum of the residues (flonicamid and its metabolites) was higher in the vinyl house with shade cover than in the glass house, under various conditions. The total residues were significantly higher when the treatment was applied under high light shade (75%). The flonicamid half-life decreased from 47.2 days (under normal conditions) to 28.4 days (at high temperatures) in the glass house, while it increased from 47.9 days (no shade cover) to 66 days (75% light shading) in the vinyl house. High humidity leads to decreases in the total sum of flonicamid residues in red bell pepper grown in a glass house, because it leads to an increase in the rate of water loss, which in turn accelerates the volatilization of the pesticide. For safety reasons, it is advisable to grow red bell pepper under glass house conditions because of the effects of solar radiation, which increases the rate of flonicamid degradation into its metabolites.

  1. Internal exposure to neutron-activated {sup 56}Mn dioxide powder in Wistar rats. Pt. 2. Pathological effects

    Shichijo, Kazuko; Mussazhanova, Zhanna; Niino, Daisuke; Nakashima, Masahiro; Tomonaga, Masao [Nagasaki University, Nagasaki (Japan); Fujimoto, Nariaki; Hoshi, Masaharu [Hiroshima University, Hiroshima (Japan); Uzbekov, Darkhan; Kairkhanova, Ynkar; Saimova, Aisulu; Chaizhunusova, Nailya; Sayakenov, Nurlan; Shabdarbaeva, Dariya; Aukenov, Nurlan; Rakhypbekov, Tolebay [Semey State Medical University, Semey (Kazakhstan); Azimkhanov, Almas; Kolbayenkov, Alexander [National Nuclear Center of the Republic of Kazakhstan, Kurchatov (Kazakhstan); Zhumadilov, Kassym [L.N. Gumilyov Eurasian National University, Astana (Kazakhstan); Stepanenko, Valeriy [A. Tsyb Medical Radiological Research Center, National Medical Research Radiological Center, Ministry of Health of Russian Federation, Obninsk, Kaluga region (Russian Federation)


    To fully understand the radiation effects of the atomic bombing of Hiroshima and Nagasaki among the survivors, radiation from neutron-induced radioisotopes in soil and other materials should be considered in addition to the initial radiation directly received from the bombs. This might be important for evaluating the radiation risks to the people who moved to these cities soon after the detonations and probably inhaled activated radioactive ''dust.'' Manganese-56 is known to be one of the dominant radioisotopes produced in soil by neutrons. Due to its short physical half-life, {sup 56}Mn emits residual radiation during the first hours after explosion. Hence, the biological effects of internal exposure of Wistar rats to {sup 56}Mn were investigated in the present study. MnO{sub 2} powder was activated by a neutron beam to produce radioactive {sup 56}Mn. Rats were divided into four groups: those exposed to {sup 56}Mn, to non-radioactive Mn, to {sup 60}Co γ rays (2 Gy, whole body), and those not exposed to any additional radiation (control). On days 3, 14, and 60 after exposure, the animals were killed and major organs were dissected and subjected to histopathological analysis. As described in more detail by an accompanying publication, the highest internal radiation dose was observed in the digestive system of the rats, followed by the lungs. It was found that the number of mitotic cells increased in the small intestine on day 3 after {sup 56}Mn and {sup 60}Co exposure, and this change persisted only in {sup 56}Mn-exposed animals. Lung tissue was severely damaged only by exposure to {sup 56}Mn, despite a rather low radiation dose (less than 0.1 Gy). These data suggest that internal exposure to {sup 56}Mn has a significant biological impact on the lungs and small intestine. (orig.)

  2. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.

    Basaria, Shehzad; Collins, Lauren; Dillon, E Lichar; Orwoll, Katie; Storer, Thomas W; Miciek, Renee; Ulloor, Jagadish; Zhang, Anqi; Eder, Richard; Zientek, Heather; Gordon, Gilad; Kazmi, Syed; Sheffield-Moore, Melinda; Bhasin, Shalender


    Concerns about potential adverse effects of testosterone on prostate have motivated the development of selective androgen receptor modulators that display tissue-selective activation of androgenic signaling. LGD-4033, a novel nonsteroidal, oral selective androgen receptor modulator, binds androgen receptor with high affinity and selectivity. Objectives. To evaluate the safety, tolerability, pharmacokinetics, and effects of ascending doses of LGD-4033 administered daily for 21 days on lean body mass, muscle strength, stair-climbing power, and sex hormones. In this placebo-controlled study, 76 healthy men (21-50 years) were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days. Blood counts, chemistries, lipids, prostate-specific antigen, electrocardiogram, hormones, lean and fat mass, and muscle strength were measured during and for 5 weeks after intervention. LGD-4033 was well tolerated. There were no drug-related serious adverse events. Frequency of adverse events was similar between active and placebo groups. Hemoglobin, prostate-specific antigen, aspartate aminotransferase, alanine aminotransferase, or QT intervals did not change significantly at any dose. LGD-4033 had a long elimination half-life and dose-proportional accumulation upon multiple dosing. LGD-4033 administration was associated with dose-dependent suppression of total testosterone, sex hormone-binding globulin, high density lipoprotein cholesterol, and triglyceride levels. follicle-stimulating hormone and free testosterone showed significant suppression at 1.0-mg dose only. Lean body mass increased dose dependently, but fat mass did not change significantly. Hormone levels and lipids returned to baseline after treatment discontinuation. LGD-4033 was safe, had favorable pharmacokinetic profile, and increased lean body mass even during this short period without change in prostate-specific antigen. Longer randomized trials should evaluate its efficacy in improving physical function

  3. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers

    Volak, Laurie P; Hanley, Michael J; Masse, Gina; Hazarika, Suwagmani; Harmatz, Jerold S; Badmaev, Vladimir; Majeed, Muhammed; Greenblatt, David J; Court, Michael H


    Aims Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers. Methods A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing. Results Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05–0.08 μm and 0.6 μm, respectively). Conclusion The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes. PMID:22725836


    Perfluorooctane sulfonate (PFOS) is a perfluoroalky1 acid (PFAA) and a persistent environmental contaminant found in the tissues of humans and wildlife. Although blood levels of PFOS have begun to decline, health concerns remain because of the long half-life of PFOS in humans. Li...

  5. The effect of AZD2171- or sTRAIL/Apo2L-loaded polylactic-co-glycolic acid microspheres on a subcutaneous glioblastoma model.

    Shivinsky, Anna; Bronshtein, Tomer; Haber, Tom; Machluf, Marcelle


    Studies with AZD2171-a new anti-angiogenic inhibitor of tyrosine kinases associated with VEGF signaling-have shown great promise for treating glioblastoma. Unfortunately, AZD2171 success is limited by low permeability through the blood-brain barrier. Due to AZD2171's short half-life and high toxicity, its local administration will require multiple intracranial procedures, making this approach clinically unfeasible. In this study, we investigated the potential of the highly hydrophobic AZD2171, released from modified polylactic-co-glycolic acid microspheres (PLGA-MS), to treat glioblastoma. To further demonstrate the versatile loading capacity of this system, the same PLGA formulation, which was found optimal for the loading and release of AZD2171, was tested with sTRAIL/Apo2L-a biologic drug that is very different than AZD2171 in its molecular weight, solubility, and charge. AZD2171 released from PLGA-MS was at least effective as the free drug in inhibiting endothelial growth and proliferation (in vitro), and, surprisingly, had a profound cytotoxic effect also towards in vitro cultured glioblastoma cell-lines (U87 and A172). Complete tumor inhibition was achieved following a single treatment with AZD2171-loaded PLGA-MS (6 (mg)/kg) administered locally adjacent to human U87 glioma tumors inoculated subcutaneously in nude mice. This improved effect, compared to other therapeutic approaches involving AZD2171, was shown to affect both tumor vasculature and the glioma cells. sTRAIL-loaded microspheres, administered at very low doses (0.3 (mg)/kg), led to 35 % inhibition of tumor growth in 2 weeks. Collectively, our results provide pre-clinical evidence for the potential of PLGA formulations of AZD2171 and sTRAIL to serve as an effective treatment for glioblastoma.

  6. Medical applications of Cu, Zn, and S isotope effects.

    Albarede, Francis; Télouk, Philippe; Balter, Vincent; Bondanese, Victor P; Albalat, Emmanuelle; Oger, Philippe; Bonaventura, Paola; Miossec, Pierre; Fujii, Toshiyuki


    This review examines recent applications of stable copper, zinc and sulfur isotopes to medical cases and notably cancer. The distribution of the natural stable isotopes of a particular element among coexisting molecular species varies as a function of the bond strength, the ionic charge, and the coordination, and it also changes with kinetics. Ab initio calculations show that compounds in which a metal binds to oxygen- (sulfate, phosphate, lactate) and nitrogen-bearing moieties (histidine) favor heavy isotopes, whereas bonds with sulfur (cysteine, methionine) favor light isotopes. Oxidized cations (e.g., Cu(ii)) and low coordination numbers are expected to favor heavy isotopes relative to their reduced counterparts (Cu(i)) and high coordination numbers. Here we discuss the first observations of Cu, Zn, and S isotopic variations, three elements closely related along multiple biological pathways, with emphasis on serum samples of healthy volunteers and of cancer patients. It was found that heavy isotopes of Zn and to an even greater extent Cu are enriched in erythrocytes relative to serum, while the difference is small for sulfur. Isotopic variations related to age and sex are relatively small. The (65)Cu/(63)Cu ratio in the serum of patients with colon, breast, and liver cancer is conspicuously low relative to healthy subjects. The characteristic time over which Cu isotopes may change with disease progression (a few weeks) is consistent with both the turnover time of the element and albumin half-life. A parallel effect on sulfur isotopes is detected in a few un-medicated patients. Copper in liver tumor tissue is isotopically heavy. In contrast, Zn in breast cancer tumors is isotopically lighter than in healthy breast tissue. (66)Zn/(64)Zn is very similar in the serum of cancer patients and in controls. Possible reasons for Cu isotope variations may be related to the cytosolic storage of Cu lactate (Warburg effect), release of intracellular copper from cysteine

  7. S-(N, N-diethylcarbamoyl)glutathione (carbamathione), a disulfiram metabolite and its effect on nucleus accumbens and prefrontal cortex dopamine, GABA, and glutamate: A microdialysis study

    Faiman, Morris D.; Kaul, Swetha; Latif, Shaheen A.; Williams, Todd D.; Lunte, Craig E.


    Disulfiram (DSF), used for the treatment of alcohol use disorders (AUDs) for over six decades, most recently has shown promise for treating cocaine dependence. Although DSF’s mechanism of action in alcohol abuse is due to the inhibition of liver mitochondrial aldehyde dehydrogenase (ALDH2), its mechanism of action in the treatment of cocaine dependence is unknown. DSF is a pro-drug, forming a number of metabolites each with discrete pharmacological actions. One metabolite formed during DSF bioactivation is S-(N, N-diethylcarbamoyl) glutathione (carbamathione) (carb). We previously showed that carb affects glutamate binding. In the present studies, we employed microdialysis techniques to investigate the effect of carb administration on dopamine (DA), GABA, and glutamate (Glu) in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), two brain regions implicated in substance abuse dependence. The effect of DSF on DA, GABA, and Glu in the NAc also was determined. Both studies were carried out in male rats. Carb (20, 50, 200 mg/kg i v) in a dose-dependent manner increased DA, decreased GABA, and had a biphasic effect on Glu, first increasing and then decreasing Glu in both the NAc and mPFC. These changes all occurred concurrently. After carb administration, NAc and mPFC carb, as well as carb in plasma, were rapidly eliminated with a half-life for each approximately 4 min, while the changes in DA, GABA, and GLu in the NAc and mPFC persisted for approximately two hours. The maximal increase in carb (Cmax) in the NAc and mPFC after carb administration was dose-dependent, as was the area under the curve (AUC). DSF (200 mg/kg i p) also increased DA, decreased GABA, and had a biphasic effect on Glu in the NAc similar to that observed in the NAc after carb administration. When the cytochrome P450 inhibitor N-benzylimidazole (NBI) (20 mg/kg i p) was administered before DSF dosing, no carb could be detected in the NAc and plasma and also no changes in NAc DA, GABA

  8. Effect of insulin on the rates of synthesis and degradation of GLUT1 and GLUT4 glucose transporters in 3T3-L1 adipocytes.

    Sargeant, R J; Pâquet, M R


    The effect of continuous insulin stimulation on the rates of turnover and on the total cellular contents of the glucose-transporter proteins GLUT1 and GLUT4 in 3T3-L1 adipocytes was investigated. Pulse-and-chase studies with [35S]methionine followed by immunoprecipitation of GLUT1 and GLUT4 with isoform-specific antibodies revealed the half-lives of these proteins to be 19 h and 50 h respectively. Inclusion of 100 nM insulin in the chase medium resulted in a decrease in the half-lives of both proteins to about 15.5 h. This effect of insulin was specific for the glucose-transporter proteins, as the average half-life of all proteins was found to be 55 h both with and without insulin stimulation. The effect of insulin on the rate of synthesis of the glucose transporters was determined by the rate of incorporation of [35S]methionine. After 24 h of insulin treatment, the rate of synthesis of GLUT1 and GLUT4 were elevated over control levels by 3.5-fold and 2-fold respectively. After 72 h of treatment under the same conditions, the rate of synthesis of GLUT1 remained elevated by 2.5-fold, whereas the GLUT4 synthesis rate was not different from control levels. Western-blot analysis of total cellular membranes revealed a 4.5-fold increase in total cellular GLUT1 content and a 50% decrease in total cellular GLUT4 after 72 h of insulin treatment. These observations suggest that the rates of synthesis and degradation of GLUT1 and GLUT4 in 3T3-L1 adipocytes are regulated independently and that these cells respond to prolonged insulin treatment by altering the metabolism of GLUT1 and GLUT4 proteins in a specific manner. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8457217

  9. Effect of peritumoral injection of boanmycin hydrochloride within temperature-sensitive in situ gel using Hep-G2 hepatoma nude mice model

    WANG Zhi-hui; DING Wei-ming; HU Xiang-dong; LI Mei; XU Hong-zhang; QIAN Lin-xue


    Background Boanmycin hydrochloride,a new antitumor agent,has a short half-life and fast clearance speed in vivo.The aim of this research was to investigate the effectiveness of peritumor injection of boanmycin hydrochloride within temperature-sensitive gel in situ using Hep-G2 hepatoma nude mice model.Methods Nude mice with human Hep-G2 tumor in right flank were randomly divided into four groups: normal saline group,in situ gel only group,boanmycin hydrochloride in situ saline group,and boanmycin hydrochloride in situ gel group,and were treated with injection of corresponding agents into peripheral tissue of the tumor.The volume of the tumor and the body weight of the mice were regularly measured,and tumor growth curve was generated.The size,internal echo,and blood flow of the tumors were observed by color Doppler ultrasonography.Histopathologic changes of the tumor after treatment were observed under both optical and transmission electron microscopy.Results The tumor growth was significantly inhibited by peritumoral therapy in boanmycin hydrochloride in situ gel group with the tumor inhibitory rate of 86.76%,The blood flow of the tumor was still seen in both normal saline group and in situ gel only group on color Doppler ultrasound.Punctate calcification and dotted blood flow were seen in boanmycin hydrochloride group; however,there was massive calcification and no blood flow in the tumor in the boanmycin hydrochloride in situ gel group.Large areas of necrosis and apoptotic cells were shown by microscopic observation in boanmycin hydrochloride in situ gel group.Conclusion Temperature-sensitive boanmycin hydrochloride in situ gel can effectively delay the release of boanmycin hydrochloride and increase its anticancer effects for liver cancer in animal model.

  10. Effect of morin on pharmacokinetics of piracetam in rats, in vitro enzyme kinetics and metabolic stability assay using rapid UPLC method.

    Sahu, Kapendra; Shaharyar, Mohammad; Siddiqui, Anees A


    The aim of this study was to investigate the effect of Morin on the pharmacokinetics of Piracetam in rats, in vitro enzyme kinetics and metabolic stability (high throughput) studies using human liver microsomes in UPLC. For pharmacokinetics studies, male Wistar rats were pretreated with Morin (10 mg/kg) for one week and on the last day, a single dose of Piracetam (50 mg/kg) was given orally. In another group, both Morin and Piracetam were co-administered to evaluate the acute effect of Morin on Piracetam. The control group received oral distilled water for one week and administered with Piracetam on the last day. As Morin is an inhibitor of P- Glycoprotein (P-gp) and CYP 3A, it was anticipated to improve the bioavailability of Piracetam. Amazingly, relative to control, the areas under the concentration time curve and peak plasma concentration of Piracetam were 1.50- and 1.45-fold, respectively, greater in the Morin-pretreated group. However, co-administration of Morin had no significant effect on these parameters. Apart from the aforementioned merits, the results of this study are further confirmed by clinical trials; Piracetam dosages should be adjusted to avoid potential drug interaction when Piracetam is used clinically in combination with Morin and Morin-containing dietary supplements. The in vitro enzyme kinetics were performed to determined km, Vmax & CLins . The in vitro metabolic stability executed for the estimation of metabolic rate constant and half-life of Piracetam. These studies also extrapolate to in vivo intrinsic hepatic clearance (Clint, in vivo ) from in vitro intrinsic hepatic clearance (CLint, in vitro ). Copyright © 2012 John Wiley & Sons, Ltd.

  11. The effect of circadian rhythm on pharmacokinetics and metabolism of the Cdk inhibitor, roscovitine, in tumor mice model.

    Sallam, Hatem; El-Serafi, Ahmed T; Filipski, Elisabeth; Terelius, Ylva; Lévi, Francis; Hassan, Moustapha


    Roscovitine is a selective Cdk-inhibitor that is under investigation in phase II clinical trials under several conditions, including chemotherapy. Tumor growth inhibition has been previously shown to be affected by the dosing time of roscovitine in a Glasgow osteosarcoma xenograft mouse model. In the current study, we examined the effect of dose timing on the pharmacokinetics, biodistribution and metabolism of this drug in different organs in B6D2F1 mice. The drug was orally administered at resting (ZT3) or activity time of the mice (ZT19) at a dose of 300 mg/kg. Plasma and organs were removed at serial time points (10, 20 and 30 min; 1, 2, 4, 6, 8, 12 and 24 h) after the administration. Roscovitine and its carboxylic metabolite concentrations were analyzed using HPLC-UV, and pharmacokinetic parameters were calculated in different organs. We found that systemic exposure to roscovitine was 38% higher when dosing at ZT3, and elimination half-life was double compared to when dosing at ZT19. Higher organ concentrations expressed as (organ/plasma) ratio were observed when dosing at ZT3 in the kidney (180%), adipose tissue (188%), testis (132%) and lungs (112%), while the liver exposure to roscovitine was 120% higher after dosing at ZT19. The metabolic ratio was approximately 23% higher at ZT19, while the intrinsic clearance (CLint) was approximately 67% higher at ZT19, indicating faster and more efficient metabolism. These differences may be caused by circadian differences in the absorption, distribution, metabolism and excretion processes governing roscovitine disposition in the mice. In this article, we describe for the first time the chronobiodistribution of roscovitine in the mouse and the contribution of the dosing time to the variability of its metabolism. Our results may help in designing better dosing schedules of roscovitine in clinical trials.

  12. Effect of solar radiation on multidrug resistant E. coli strains and antibiotic mixture photodegradation in wastewater polluted stream.

    Rizzo, L; Fiorentino, A; Anselmo, A


    The effect of solar radiation on the inactivation of multidrug resistant Escherichia coli (MDR) strains selected from an urban wastewater treatment plant (UWWTP) effluent and the change of their resistance to a mixture of three antibiotics (evaluated in terms of minimum inhibit concentration (MIC)) in wastewater polluted stream were investigated. The solar photodegradation of the mixture of the three target antibiotics (amoxicillin (AMX), ciprofloxacin (CPX), and sulfamethoxazole (SMZ)) was also evaluated. Additionally, since UWWTP effluents are possible sources of antibiotics and antibiotic resistant bacteria, the disinfection by conventional chlorination process of the UWWTP effluent inoculated with MDR strains was investigated too. Solar radiation poorly affected the inactivation of the two selected antibiotic resistant E. coli strains (40 and 60% after 180 min irradiation). Moreover, solar radiation did not affect strain resistance to AMX (MIC>256 μg/mL) and SMZ (MIC>1024 μg/mL), but affected resistance of the lower resistance strain to CPX (MIC decreased by 33% but only after 180 min of irradiation). Chlorination of wastewater sample strongly decreased the number of the two selected antibiotic resistant E. coli strains (99.667 and 99.999%), after 60 min of contact time at 2.0 mg/L initial chlorine concentration, but the resistance of survived colonies to antibiotics was unchanged. Finally, the solar photodegradation rate of the antibiotic mixture (1mg/L initial concentration respectively) resulted in the following order (half-life time): CPX (t(1/2)=24 min)resistance to SMZ in surface water is significantly higher compared to CPX and AMX. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Immediate and Persistent Effects of Salvinorin A on the Kappa Opioid Receptor in Rodents, Monitored In Vivo with PET.

    Placzek, Michael S; Van de Bittner, Genevieve C; Wey, Hsiao-Ying; Lukas, Scott E; Hooker, Jacob M


    Monitoring changes in opioid receptor binding with positron emission tomography (PET) could lead to a better understanding of tolerance and addiction because altered opioid receptor dynamics following agonist exposure has been linked to tolerance mechanisms. We have studied changes in kappa opioid receptor (KOR) binding availability in vivo with PET following kappa opioid agonist administration. Male Sprague-Dawley rats (n=31) were anesthetized and treated with the (KOR) agonist salvinorin A (0.01-1.8 mg/kg, i.v.) before administration of the KOR selective radiotracer [(11)C]GR103545. When salvinorin A was administered 1 min prior to injection of the radiotracer, [(11)C]GR103545 binding potential (BPND) was decreased in a dose-dependent manner, indicating receptor binding competition. In addition, the unique pharmacokinetics of salvinorin A (half-life ~8 min in non-human primates) allowed us to study the residual impact on KOR after the drug had eliminated from the brain. Salvinorin A was administered up to 5 h prior to [(11)C]GR103545, and the changes in BPND were compared with baseline, 2.5 h, 1 h, and 1 min pretreatment times. At lower doses (0.18 mg/kg and 0.32 mg/kg) we observed no prolonged effect on KOR binding but at 0.60 mg/kg salvinorin A induced a sustained decrease in KOR binding (BPND decreased by 40-49%) which persisted up to 2.5 h post administration, long after salvinorin A had been eliminated from the brain. These data point towards an agonist-induced adaptive response by KOR, the dynamics of which have not been previously studied in vivo with PET.

  14. N-acetyl cysteine mitigates the acute effects of cocaine-induced toxicity in astroglia-like cells.

    Ramesh B Badisa

    Full Text Available Cocaine has a short half-life of only about an hour but its effects, predominantly on the central nervous system (CNS, are fairly long-lasting. Of all cells within the CNS, astrocytes may be the first to display cocaine toxicity owing to their relative abundance in the brain. Cocaine entry could trigger several early response changes that adversely affect their survival, and inhibiting these changes could conversely increase their rate of survival. In order to identify these changes and the minimal concentrations of cocaine that can elicit them in vitro, rat C6 astroglia-like cells were treated with cocaine (2-4 mM for 1h and assayed for alterations in gross cell morphology, cytoplasmic vacuolation, viability, reactive oxygen species (ROS generation, glutathione (GSH levels, cell membrane integrity, F-actin cytoskeleton, and histone methylation. We report here that all of the above identified features are significantly altered by cocaine, and may collectively represent the key pathology underlying acute toxicity-mediated death of astroglia-like cells. Pretreatment of the cells with the clinically available antioxidant N-acetyl cysteine (NAC, 5 mM for 30 min inhibited these changes during subsequent application of cocaine and mitigated cocaine-induced toxicity. Despite repeated cocaine exposure, NAC pretreated cells remained highly viable and post NAC treatment also increased viability of cocaine treated cells to a smaller yet significant level. We show further that this alleviation by NAC is mediated through an increase in GSH levels in the cells. These findings, coupled with the fact that astrocytes maintain neuronal integrity, suggest that compounds which target and mitigate these early toxic changes in astrocytes could have a potentially broad therapeutic role in cocaine-induced CNS damage.

  15. Effect of dynamic crosslinking on phase morphology and mechanical properties of polyamide 6,12/ethylene vinyl acetate copolymer blends

    Fabrício Bondan


    Full Text Available The dynamic crosslinking of polyamide 6,12 and ethylene vinyl acetate (PA6,12/EVA blends in the mixing chamber of a torque rheometer was investigated. EVA was selectively crosslinked within the PA6,12 phase through free radical reactions using dycumil peroxide. The degree of EVA crosslinking in the PA12,6/EVA materials was estimated based on the gel content (insoluble EVA fraction. The PA6,12/EVA phase morphology was investigated by scanning electron microscopy. The mechanical properties were investigated by determining the tensile strength and hardness. The half-life time ( for homolytic scission of the dcumil peroxide (DCP was ~6s, and this time is longer than the dispersion time of the DCP in the blends. The addition of DCP resulted in increased torque values due to specific crosslinking in the EVA phase. For the pure EVA and its blends with PA6,12 the stabilized torque values increased proportionally with the amount of DCP in the system, due to a higher degree of crosslinking of the elastomeric phase. The gel content of the dynamically crosslinked blends increased with the amount of DCP incorporated until 4 phr. At 1 phr the gel content value was 2.6wt.%, while at 4 phr it was 17wt.%. For the polymer blend with 8 phr of DCP a lubricating effect contributed to reducing the gel content. The dynamically crosslinked blends, regardless of the amount of DCP added, showed a reduction in the mechanical properties, which is related to the morphological features of the system due to the low mechanical fragmentation during melt processing.

  16. Tellurium isotopic composition of the early solar system—A search for effects resulting from stellar nucleosynthesis, 126Sn decay, and mass-independent fractionation

    Fehr, Manuela A.; Rehkämper, Mark; Halliday, Alex N.; Wiechert, Uwe; Hattendorf, Bodo; Günther, Detlef; Ono, Shuhei; Eigenbrode, Jennifer L.; Rumble, Douglas


    New precise Te isotope data acquired by multiple collector inductively coupled plasma mass spectrometry (MC-ICPMS) are presented for selected extraterrestrial and terrestrial materials. Bulk samples of carbonaceous, ordinary and enstatite chondrites as well as the metal and sulfide phases of iron meteorites were analyzed to search for nucleosynthetic isotope anomalies and to find evidence of formerly live 126Sn, which decays to 126Te with a half-life of 234,500 yr. None of the meteorites show evidence of mass dependent Te isotope fractionations larger than 2‰ for δ 126/128Te. Following internal normalization of the data to 125Te/ 128Te, the Te isotope ratios of all analyzed meteorites were found to be identical to a terrestrial standard, within uncertainties. This provides evidence that the regions of the solar disk that were sampled during accretion of the meteorite parent bodies were well mixed and homogeneous on a large scale, with respect to Te isotopes. The data acquired for bulk carbonaceous chondrites indicate that the initial 126Sn/ 118Sn ratio of the solar system was <4 × 10 -5, but this is dependent on the assumption that no redistribution of Sn and Te occurred since the start of the solar system. Five Archean sedimentary sulfides that display both mass dependent and mass-independent isotope effects for S yield internally normalized Te isotope data, which indicate that mass-independent Te isotope effects are absent. The mass dependent fractionations in these samples are constrained to be less than ˜1‰ for δ 126/128Te.

  17. PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury.

    Ruozi, Barbara; Belletti, Daniela; Sharma, Hari S; Sharma, Aruna; Muresanu, Dafin F; Mössler, Herbert; Forni, Flavio; Vandelli, Maria Angela; Tosi, Giovanni


    Cerebrolysin is a peptide mixture able to ameliorate symptomatology and delay progression of neurological disorders such as Alzheimer's disease and dementia. The administration of this drug in humans presents several criticisms due to its short half-life, poor stability, and high doses needed to achieve the effect. This paper investigates the potential of polylactic-co-glycolide (PLGA) nanoparticles (NPs) as sustained release systems for iv administration of cerebrolysin in normal and brain injured rats. NPs were prepared by water-in-oil-in-water (w/o/w) double emulsion technique and characterized by light scattering for mean size and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The NPs produced by double sonication under cooling at 60 W for 45 s, 12 mL of 1 % w:v of PVA, and 1:0.6 w:w drug/PLGA ratio (C-NPs4) displayed an adequate loading of drug (24 ± 1 mg/100 mg of NPs), zeta potential value (-13 mV), and average diameters (ranged from 250 to 330 nm) suitable to iv administration. SEM images suggested that cerebrolysin was molecularly dispersed into matricial systems and partially adhered to the NP surface. A biphasic release with an initial burst effect followed by sustained release over 24 h was observed. Long-term stability both at room and at low temperature of freeze-dried NPs was investigated. To gain deeper insight into NP stability after in vivo administration, the stability of the best NP formulation was also tested in serum. These PLGA NPs loaded with cerebrolysin were able to reduce brain pathology following traumatic brain injury. However, the size, the polydispersivity, and the surface properties of sample were significantly affected by the incubation time and the serum concentration.

  18. [Study on compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma based on pharmacokinetics of effective components salvianolic acid B and ferulic acid in rat plasma].

    Zhang, Cui-ying; Zhang, Hong; Dong, Yu; Ren, Wei-guang; Chen, Heng-wen


    A study was made on the pharmacokinetic regularity of effective components salvianolic acid B and ferulic acid in Salviae Miltiorrhizae Radix et Rhizoma (SMRR) and Chuanxiong Rhizoma(CR) in rats, so as to discuss the compatibility mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma. Rats were randomly divided into three groups and intravenously injected with 50 mg x kg(-1) salvianolic acid B for the single SMRR extracts group, 0.5 mg x kg(-1) ferulic acid for the single CR extracts group and 50 mg x kg(-1) salvianolic acid B + 0.5 mg x kg(-1) ferulic acid for the SMRR and CR combination group. The blood samples were collected at different time points and purified by liquid-liquid extraction with ethyl acetate. With chloramphenicol as internal standard (IS), UPLC was adopted to determine concentrations of salvianolic acid B and ferulic acid. The pharmacokinetic parameters of salvianolic acid B and ferulic acid were calculated with WinNonlin 6.2 software and analyzed by SPSS 19.0 statistical software. The UPLC analysis method was adopted to determine salvianolic acid B and ferulic acid in rat plasma, including linear equation, stability, repeatability, precision and recovery. The established sample processing and analysis methods were stable and reliable, with significant differences in major pharmacokinetic parameters, e.g., area under the curve (AUC), mean residence time (MRT) and terminal half-life (t(1/2)). According to the experimental results, the combined application of SMRR and CR can significantly impact the pharmacokinetic process of their effective components in rats and promote the wide distribution, shorten the action time and prolong the in vivo action time of salvianolic acid B and increase the blood drug concentration and accelerate the clearance of ferulic acid in vivo.

  19. The effect of nitrification inhibitors on nitrous oxide emissions from cattle urine depositions to grassland under summer conditions in the UK.

    Barneze, A S; Minet, E P; Cerri, C C; Misselbrook, T


    Nitrous oxide (N2O) has become the prime ozone depleting atmospheric emission and the third most important anthropogenic greenhouse gas, with a global warming potential approximately 300 times higher than CO2. Nitrification and denitrification are processes responsible for N2O emission from the soil after nitrogen input. The application of a nitrification inhibitor can reduce N2O emissions from these processes. The objective of this study was to assess the effect of two different nitrification inhibitors (dicyandiamide (DCD) and a commercial formulation containing two pyrazole derivatives (PD), 1H-1,2,4-triazole and 3-methylpyrazole) on N2O emissions from cattle urine applications for summer grazing conditions in the UK. Experiments were conducted under controlled conditions in a laboratory incubator and under field conditions on a grassland soil. The N2O emissions showed similar temporal dynamics in both experiments. DCD concentration in the soil showed an exponential degradation during the experiment, with a half-life of the order of only 10d (air temperature c. 15 °C). DCD (10 kg ha(-1)) and PD at the highest application rate (3.76 kg ha(-1)) reduced N2O emissions by 13% and 29% in the incubation experiment and by 33% and 6% in the field experiment, respectively, although these reductions were not statistically significant (P>0.05). Under UK summer grazing conditions, these nitrification inhibitors appear to be less effective at reducing N2O emissions than reported for other conditions elsewhere in the literature, presumably due to the higher soil temperature.

  20. Gene Expression Profiling in Wild-Type and PPAR-Null Mice Exposed to Perfluorooctane Sulfonate Reveals PPAR-Independent Effects

    Mitchell B. Rosen


    Full Text Available Perfluorooctane sulfonate (PFOS is a perfluoroalkyl acid (PFAA and a persistent environmental contaminant found in the tissues of humans and wildlife. Although blood levels of PFOS have begun to decline, health concerns remain because of the long half-life of PFOS in humans. Like other PFAAs, such as, perfluorooctanoic acid (PFOA, PFOS is an activator of peroxisome proliferator-activated receptor-alpha (PPAR and exhibits hepatocarcinogenic potential in rodents. PFOS is also a developmental toxicant in rodents where, unlike PFOA, its mode of action is independent of PPAR. Wild-type (WT and PPAR-null (Null mice were dosed with 0, 3, or 10 mg/kg/day PFOS for 7 days. Animals were euthanized, livers weighed, and liver samples collected for histology and preparation of total RNA. Gene profiling was conducted using Affymetrix 430_2 microarrays. In WT mice, PFOS induced changes that were characteristic of PPAR transactivation including regulation of genes associated with lipid metabolism, peroxisome biogenesis, proteasome activation, and inflammation. PPAR-independent changes were indicated in both WT and Null mice by altered expression of genes related to lipid metabolism, inflammation, and xenobiotic metabolism. Such results are similar to studies done with PFOA and are consistent with modest activation of the constitutive androstane receptor (CAR, and possibly PPAR and/or PPAR/. Unique treatment-related effects were also found in Null mice including altered expression of genes associated with ribosome biogenesis, oxidative phosphorylation, and cholesterol biosynthesis. Of interest was up-regulation of Cyp7a1, a gene which is under the control of various transcription regulators. Hence, in addition to its ability to modestly activate PPAR, PFOS induces a variety of PPAR-independent effects as well.