34 CFR 674.42 - Contact with the borrower.

Code of Federal Regulations, 2010 CFR

2010-07-01

... half-time study at the institution or during the exit interview. If the borrower enters the repayment... exit counseling is conducted shortly before the borrower ceases at least half-time study at the institution. As an alternative, in the case of a student enrolled in a correspondence program or a study...

34 CFR 674.42 - Contact with the borrower.

Code of Federal Regulations, 2013 CFR

2013-07-01

... half-time study at the institution or during the exit interview. If the borrower enters the repayment... exit counseling is conducted shortly before the borrower ceases at least half-time study at the institution. As an alternative, in the case of a student enrolled in a correspondence program or a study...

34 CFR 674.42 - Contact with the borrower.

Code of Federal Regulations, 2014 CFR

2014-07-01

... half-time study at the institution or during the exit interview. If the borrower enters the repayment... exit counseling is conducted shortly before the borrower ceases at least half-time study at the institution. As an alternative, in the case of a student enrolled in a correspondence program or a study...

34 CFR 674.42 - Contact with the borrower.

Code of Federal Regulations, 2011 CFR

2011-07-01

... half-time study at the institution or during the exit interview. If the borrower enters the repayment... exit counseling is conducted shortly before the borrower ceases at least half-time study at the institution. As an alternative, in the case of a student enrolled in a correspondence program or a study...

34 CFR 674.32 - Special terms: loans to less than half-time student borrowers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false Special terms: loans to less than half-time student borrowers. 674.32 Section 674.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Terms of...

34 CFR 674.32 - Special terms: loans to less than half-time student borrowers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Special terms: loans to less than half-time student borrowers. 674.32 Section 674.32 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Terms of...

34 CFR 674.37 - Deferment of repayment-NDSLs made before October 1, 1980 and Defense loans.

Code of Federal Regulations, 2014 CFR

2014-07-01

... loan, when the borrower is at least a half-time regular student at— (i) An institution of higher... regular student for a full academic year and intends to enroll as at least half-time regular student in..., Marines or Coast Guard (see § 674.59); (2) A Peace Corps volunteer (see § 674.60); or (3) A volunteer...

34 CFR 674.37 - Deferment of repayment-NDSLs made before October 1, 1980 and Defense loans.

Code of Federal Regulations, 2013 CFR

2013-07-01

... loan, when the borrower is at least a half-time regular student at— (i) An institution of higher... regular student for a full academic year and intends to enroll as at least half-time regular student in..., Marines or Coast Guard (see § 674.59); (2) A Peace Corps volunteer (see § 674.60); or (3) A volunteer...

34 CFR 674.37 - Deferment of repayment-NDSLs made before October 1, 1980 and Defense loans.

Code of Federal Regulations, 2012 CFR

2012-07-01

... loan, when the borrower is at least a half-time regular student at— (i) An institution of higher... regular student for a full academic year and intends to enroll as at least half-time regular student in..., Marines or Coast Guard (see § 674.59); (2) A Peace Corps volunteer (see § 674.60); or (3) A volunteer...

Rapid Suppression of Growth by Blue Light 1

PubMed Central

Cosgrove, Daniel J.; Green, Paul B.

1981-01-01

The mechanism of the rapid inhibition of hypocotyl elongation by blue light was investigated in cucumber (Cucumis sativus L.) and sunflower (Helianthus annuus L.) seedlings by measuring the changes in turgor during the response. A special device, based on the resonance frequency principle, was built which permitted simultaneous and continuous measurements of both tissue rigidity (turgor) and growth rate on a single intact hypocotyl. The large decrease in growth rate following blue irradiation was consistently accompanied by a small increase in resonance frequency. This result indicates that blue light inhibits growth by decreasing the yielding properties of the cell walls, resulting in a slight rise in turgor because of the coupling between growth rate and turgor. The nature of the blue-light inhibition was further studied by measuring the influence of light dose and temperature on the time course of inhibition (lag-time, half-time of inhibition, and amount of inhibition) with the aid of a microcomputer-based system for measuring growth rate and for controlling light duration and energy. The light dose has no influence on either the lag-time or the half-time of inhibition, but strongly affects the amount of inhibition. In contrast, a 10°C drop in temperature (from 30 to 20°C) lengthened the lag-time of the blue-light response, but did not significantly affect the half-time or the per cent inhibition by blue light. The half-time for changes in hypocotyl length (induced by applying a hydrostatic pressure to the roots or to the cut end of seedlings with roots excised) was found to be the same as the half-time of the blue-light inhibition (15 to 25 seconds in cucumber; 90 to 150 seconds in sunflower). These results support the idea that blue light, after a fixed lag period, induces an immediate decrease in the yielding properties of the cell walls. The growth rate subsequently decreases with a half-time that depends on the time required for cell turgor pressures to reach their new steady-state values. PMID:16662124

Quantitative contrast-enhanced ultrasonography for the differential diagnosis of endometrial hyperplasia and endometrial neoplasms

PubMed Central

Liu, Ying; Xu, Yi; Cheng, Wen; Liu, Xinghan

2016-01-01

The present study aimed to investigate the feasibility of applying contrast-enhanced ultrasonography (CEUS) imaging technology for distinguishing between benign and malignant endometrial lesions, and to screen markers that could be correlated with the pathological results. In this study, endometrial diseases were diagnosed by biopsy under hysteroscopy and CEUS examinations. The intensity and time parameters of the time-intensity curve (TIC) were analyzed. The mean arrival time (AT), time-to-peak (TTP), rise time (RT), washout half-time and clearance half-time of malignant lesions were shorter than those of benign lesions (P<0.05), whereas the average peak intensity (PI) and enhancement intensity (EI) of malignant lesions were higher than those of benign lesions (P<0.05). The receiver operating characteristic curve showed the following cut-off values: PI, 29.2 dB; EI, 21.35 dB; AT, 12.75 sec; TTP, 26.75 sec; RT, 13.2 sec; clearance half-time, 89.3 sec; and washout half-time, 75.45 sec. The lesions with PI, an EI higher than that of the cut-off and lesions with an AT, TTP, RT, half clearing time and washout half-time shorter than the cut-off were considered malignant. The TTP, RT and half clearing time were negatively correlated with microvessel density (MVD), i.e., MVD was higher when the TTP, RT and half clearing time were shorter. Overall, changes in the enhancement and clearing of lesions could be quantitatively analyzed by CEUS TIC and further discriminate benign from malignant lesions. In the present study, CEUS appeared to indirectly reflect blood vessel changes inside the lesions and provided a pre-operative non-invasive fast imaging method for the diagnosis of endometrial disease. PMID:27895728

137Cs activity concentration in mosses in the Calabria region, south of Italy

NASA Astrophysics Data System (ADS)

Caridi, F.; Belvedere, A.; D'Agostino, M.; Marguccio, S.

2017-05-01

Many studies carried out after the Chernobyl nuclear accident in 1986 showed that mosses are suitable bioindicators of the radioactive fall-out, given their long life expectancy. 137Cs activity concentration was measured through HPGe gamma spectrometry in different mosses (Hypnum Cupressiforme, Hypnum Andoi, Homalothecium Sericeum, Philonotis Fontana), collected, in 2008 and 2015, from four sampling sites in the Calabria region, south of Italy. Experimental specific activities allowed us to determine the effective and the biological half-time of 137Cs for the investigated plants. The effective half-time was found in the range from (4.2 ± 1.1) to (7.4 ± 1.8) years; the biological half-time varied from (4.9 ± 1.3) to (9.9 ± 2.4) years. Data reported in this article provide useful information on the environmental risk of the studied area and can be further used for a radiological mapping.

The effect of papaine on the time course of the end-plate current.

PubMed

Humar, M; Kordas, M; Melik, Z

1980-07-01

Papaine is known to detach cholinesterases from the synaptic cleft. It could be expected that this would result in an increase of the amplitude and half-time of the end-plate current. Thus, the effect of papaine on the end-plate current. Thus, the effect of papaine on the end-plate current should be similar to the effect of anticholinesterase methanesulfonylfluoride. The end-plate current was recorded in frog skeletal muscle at various levels of membrane potential, before and after papaine was added to the bath. The effect of papaine was an increase of the half-time of the end-plate current, similarly as after treatment of the muscle by methanesulfonylfluoride. It seems that both papaine and methanesulfonylfluoride have a similar mechanism of action. In either experimental condition hydrolysis of transmitter is decreased or abolished, which results in an increase of the half-time of the end-plate current.

[Decompression problems in diving in mountain lakes].

PubMed

Bühlmann, A A

1989-08-01

The relationship between tolerated high-pressure tissue nitrogen and ambient pressure is practically linear. The tolerated nitrogen high pressure decreases at altitude, as the ambient pressure is lower. Additionally, tissues with short nitrogen half-times have a higher tolerance than tissues which retain nitrogen for longer duration. For the purpose of determining safe decompression routines, the human body can be regarded as consisting of 16 compartments with half-times from 4 to 635 minutes for nitrogen. The coefficients for calculation of the tolerated nitrogen-high pressure in the tissues can be deduced directly from the half-times for nitrogen. We show as application the results of 573 simulated air dives in the pressure-chamber and 544 real dives in mountain lakes in Switzerland (1400-2600 m above sea level) and in Lake Titicaca (3800 m above sea level). They are in accordance with the computed limits of tolerance.

Effect of Acylglycerol Composition and Fatty Acyl Chain Length on Lipid Digestion in pH-Stat Digestion Model and Simulated In Vitro Digestion Model.

PubMed

Qi, Jin F; Jia, Cai H; Shin, Jung A; Woo, Jeong M; Wang, Xiang Y; Park, Jong T; Hong, Soon T; Lee, K-T

2016-02-01

In this study, a pH-stat digestion model and a simulated in vitro digestion model were employed to evaluate the digestion degree of lipids depending on different acylglycerols and acyl chain length (that is, diacylglycerol [DAG] compared with soybean oil representing long-chain triacylglycerol compared with medium-chain triacylglycerol [MCT]). In the pH-stat digestion model, differences were observed among the digestion degrees of 3 oils using digestion rate (k), digestion half-time (t1/2 ), and digestion extent (Φmax). The results showed the digestion rate order was MCT > soybean oil > DAG. Accordingly, the order of digestion half-times was MCT < soybean oil < DAG. In simulated in vitro digestion model, digestion rates (k') and digestion half-times (t'1/2 ) were also obtained and the results showed a digestion rate order of MCT (k' = 0.068 min(-1) ) > soybean oil (k' = 0.037 min(-1) ) > DAG (k' = 0.024 min(-1) ). Consequently, the order of digestion half-times was MCT (t'1/2 = 10.20 min) < soybean oil (t'1/2 = 18.74 min) < DAG (t'1/2 = 29.08 min). The parameters obtained using the 2 models showed MCT was digested faster than soybean oil, and that soybean oil was digested faster than DAG. © 2015 Institute of Food Technologists®

Defining Nitrogen Kinetics for Air Break in Prebreath

NASA Technical Reports Server (NTRS)

Conkin, Johnny

2010-01-01

Actual tissue nitrogen (N2) kinetics are complex; the uptake and elimination is often approximated with a single half-time compartment in statistical descriptions of denitrogenation [prebreathe(PB)] protocols. Air breaks during PB complicate N2 kinetics. A comparison of symmetrical versus asymmetrical N2 kinetics was performed using the time to onset of hypobaric decompression sickness (DCS) as a surrogate for actual venous N2 tension. METHODS: Published results of 12 tests involving 179 hypobaric exposures in altitude chambers after PB, with and without airbreaks, provide the complex protocols from which to model N2 kinetics. DCS survival time for combined control and airbreaks were described with an accelerated log logistic model where N2 uptake and elimination before, during, and after the airbreak was computed with a simple exponential function or a function that changed half-time depending on ambient N2 partial pressure. P1N2-P2 = (Delta)P defined decompression dose for each altitude exposure, where P2 was the test altitude and P1N2 was computed N2 pressure at the beginning of the altitude exposure. RESULTS: The log likelihood (LL) without decompression dose (null model) was -155.6, and improved (best-fit) to -97.2 when dose was defined with a 240 min half-time for both N2 elimination and uptake during the PB. The description of DCS survival time was less precise with asymmetrical N2 kinetics, for example, LL was -98.9 with 240 min half-time elimination and 120 min half-time uptake. CONCLUSION: The statistical regression described survival time mechanistically linked to symmetrical N2 kinetics during PBs that also included airbreaks. The results are data-specific, and additional data may change the conclusion. The regression is useful to compute additional PB time to compensate for an airbreak in PB within the narrow range of tested conditions.

Defining Nitrogen Kinetics for Air Break in Prebreathe

NASA Technical Reports Server (NTRS)

Conkin, Johnny

2009-01-01

Actual tissue nitrogen (N2) kinetics are complex; the uptake and elimination is often approximated with a single half-time compartment in statistical descriptions of denitrogenation [prebreathe (PB)] protocols. Air breaks during PB complicate N2 kinetics. A comparison of symmetrical versus asymmetrical N2 kinetics was performed using the time to onset of hypobaric decompression sickness (DCS) as a surrogate for actual venous N2 tension. Published results of 12 tests involving 179 hypobaric exposures in altitude chambers after PB, with and without air breaks, provide the complex protocols from which to model N2 kinetics. DCS survival time for combined control and air breaks were described with an accelerated log logistic model where N2 uptake and elimination before, during, and after the air break was computed with a simple exponential function or a function that changed half-time depending on ambient N2 partial pressure. P1N2-P2 = delta P defined DCS dose for each altitude exposure, where P2 was the test altitude and P1N2 was computed N2 pressure at the beginning of the altitude exposure. The log likelihood (LL) without DCS dose (null model) was -155.6, and improved (best-fit) to -97.2 when dose was defined with a 240 min half-time for both N2 elimination and uptake during the PB. The description of DCS survival time was less precise with asymmetrical N2 kinetics, for example, LL was -98.9 with 240 min half-time elimination and 120 min half-time uptake. The statistical regression described survival time mechanistically linked to symmetrical N2 kinetics during PBs that also included air breaks. The results are data-specific, and additional data may change the conclusion. The regression is useful to compute additional PB time to compensate for an air break in PB within the narrow range of tested conditions.

Disposition of inhaled 1-chloro-2-propanol in F344/N rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, J.A.; Birnbaum, L.S.; Dahl, A.R.

1988-09-30

Propylene chlorohydrins, of which 1-chloro-2-propanol (1-CP) is a constituent, used as intermediates in the manufacture of propylene oxide and have been identified as potential air pollutants. The objective of these studies was to determine whether changes in the inhaled exposure concentration would affect the disposition of 1-CP in rats. In addition, experiments were conducted to identify the carbon atom of 1-CP that is metabolized to CO2. Rats were exposed nose-only to (14C)1-CP for 6 hr to 8.3 +/- 1.0 ppm (26.1 +/- 3.2 micrograms/liter air) or 77 +/- 4 ppm (245 +/- 13 micrograms/liter air) (mean +/- SE). There weremore » two major routes of elimination of 14C, urinary and exhalation of CO2, which together accounted for about 80% of the total 14C in excreta and carcass. Half-times for elimination of 14C in urine as 14CO2 were between 3 and 7 hr with no effect of exposure concentration on the elimination half-times for either route. After the end of exposure, kidneys, livers, trachea, and nasal turbinates contained high concentrations of (14C)1-CP equivalents at both exposure concentrations (30-50 nmol 14C/g tissue for the 8 ppm exposure level and 200-350 nmol 14C/g tissue for the 80 ppm exposure level). Elimination of 14C from tissues was biphasic with about 50% of the material in a tissue being rapidly eliminated with a half-time of 1 to 3 hr and the remaining material slowly eliminated with a half-time of 40 to 80 hr. There was no effect of exposure concentration on elimination half-times in tissues. Major metabolites detected in urine and tissues (liver, kidney, and lung) were N-acetyl-S-(hydroxypropyl)cysteine and/or S-(2-hydroxypropyl)-cysteine. Little unmetabolized 1-CP (less than 1%) was detected in analyzed tissues or urine.« less

Calculation of pressure half-time.

PubMed

Oyama, Mark A; Weidman, Jess A; Cole, Steven G

2008-06-01

Doppler echocardiography is useful in assessing the severity of obstructive cardiac lesions, such as mitral valve stenosis. The Doppler study can be used to calculate pressure half-time (PHT), which is defined as the time required for the pressure gradient across an obstruction to decrease to half of its maximal value. Thus, PHT increases as the severity of stenosis increases. In this report, we describe the methodology involved in measuring PHT in a dog with mitral valve stenosis before and after balloon valvuloplasty.

Human data demonstrating extra long retention of plutonium in the lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bihl, D.E.; Carbaugh, E.H.; Sula, M.J.

1991-01-01

Case histories are presented of 10 humans with inhalation depositions of Pu in which the Pu is retained in the lung or pulmonary lymph system for extremely long periods. The retention half-times range from 5000 to at least 20,000 d for most (in some cases all) of the initial deposition. In no case was a clearance half-time in the hundreds of days observed. The form of Pu involved in these cases is believed to be calcined Pu oxide. 9 refs., 1 fig., 2 tabs.

[Volume changes to the neck lymph node metastases in head-neck tumors. The evaluation of radiotherapeutic treatment success].

PubMed

Liszka, G; Thalacker, U; Somogyi, A; Németh, G

1997-08-01

This work is engaged with the volume change of neck lymph node metastasis of malignant tumors in the head-neck region during radiotherapy. In 54 patients with head and neck tumors, the volume of neck lymph nodes before and after radiation was measured. The volumetry was done with CT planimetry. The total dose was 66 Gy (2 Gy/d) telecobalt from 2 lateral opponated fields. The time of volume change could be defined with measuring of the half-time and the doubling-time by the help of Schwartz formula. After 10 Gy the volume diminution was about 20% and half-time 24 to 26 days. Afterwards the time of volume diminution picked up speed and finally achieved 60 to 72%. Meanwhile the half-time decreased to the half value. The result was independent of the site of primary tumor, the patient's sex and age. In our opinion the effectivity of radiotherapy can best be judged with defining of the volume change of lymph nodes of the neck.

Relationship between mercury in kidney, blood, and urine in environmentally exposed individuals, and implications for biomonitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akerstrom, Magnus, E-mail: magnus.akerstrom@amm.gu

Background: Individuals without occupational exposure are exposed to mercury (Hg) from diet and dental amalgam. The kidney is a critical organ, but there is limited information regarding the relationship between Hg in kidney (K-Hg), urine (U-Hg), blood (B-Hg), and plasma (P-Hg). Objectives: The aim was to determine the relationship between K-Hg, U-Hg, B-Hg, and P-Hg among environmentally exposed individuals, estimate the biological half-time of K-Hg, and provide information useful for biomonitoring of Hg. Methods: Kidney cortex biopsies and urine and blood samples were collected from 109 living kidney donors. Total Hg concentrations were determined and the relationships between K-Hg, U-Hg,more » P-Hg, and B-Hg were investigated in regression models. The half-time of K-Hg was estimated from the elimination constant. Results: There were strong associations between K-Hg and all measures of U-Hg and P-Hg (r{sub p} = 0.65–0.84, p < 0.001), while the association with B-Hg was weaker (r{sub p} = 0.29, p = 0.002). Mean ratios between K-Hg (in μg/g) and U-Hg/24h (in μg) and B-Hg (in μg/L) were 0.22 and 0.19 respectively. Estimates of the biological half-time varied between 30 and 92 days, with significantly slower elimination in women. Adjusting overnight urine samples for dilution using urinary creatinine resulted in less bias in relation to K-Hg or U-Hg/24h, compared with other adjustment techniques. Conclusions: The relationship between K-Hg and U-Hg is approximately linear. K-Hg can be estimated using U-Hg and gender. Women have longer half-time of Hg in kidney compared to men. Adjusting overnight urine samples for creatinine concentration resulted in less bias. - Highlights: • The first study of the relation between Hg in kidney, blood and urine at low U-Hg • Simultaneous samples were collected from healthy kidney donors. • There was a linear relationship between mercury in kidney and urine. • Kidney Hg can be estimated using U-Hg and gender. • Women have longer half-time of Hg in kidney compared to men.« less

Pharmacokinetics of fentanyl in patients undergoing abdominal aortic surgery.

PubMed

Hudson, R J; Thomson, I R; Cannon, J E; Friesen, R M; Meatherall, R C

1986-03-01

The authors determined the pharmacokinetics of fentanyl 100 micrograms X kg-1 iv in patients undergoing elective abdominal aortic surgery. The mean (+/- SD) age of the ten patients was 67.2 +/- 8.7 yr; their mean weight was 78.5 +/- 13.7 kg. Seven patients had aortic aneurysm repair, and the other three patients had aortobifemoral grafts. Serum fentanyl concentrations were determined from samples drawn at increasing intervals over a 24-h period. A three-compartment pharmacokinetic model was fit to the concentration versus time data. Total drug clearance was 9.8 +/- 1.8 ml X min-1 X kg-1. The volume of distribution at steady-state (Vdss) was 5.4 +/- 1.9 X 1 kg-1. Elimination half-time was 8.7 +/- 2.5 h. There were no significant correlations between these pharmacokinetic parameters and patient's age, duration of aortic cross-clamping, duration of surgery, intraoperative blood loss, or volume of iv fluids given intraoperatively. In healthy volunteers or patients undergoing general surgery, other investigators report mean elimination half-times for fentanyl ranging from 1.7 to 4.4 h. The prolonged elimination half-time in patients having abdominal aortic surgery has important clinical implications. In particular, recovery from large doses will take much longer than would have been anticipated from previously published fentanyl pharmacokinetic data.

Ecologically Valid Carbohydrate Intake during Soccer-Specific Exercise Does Not Affect Running Performance in a Fed State

PubMed Central

Funnell, Mark P.; Dykes, Nick R.; Owen, Elliot J.; Mears, Stephen A.; Rollo, Ian; James, Lewis J.

2017-01-01

This study assessed the effect of carbohydrate intake on self-selected soccer-specific running performance. Sixteen male soccer players (age 23 ± 4 years; body mass 76.9 ± 7.2 kg; predicted VO2max = 54.2 ± 2.9 mL∙kg−1∙min−1; soccer experience 13 ± 4 years) completed a progressive multistage fitness test, familiarisation trial and two experimental trials, involving a modified version of the Loughborough Intermittent Shuttle Test (LIST) to simulate a soccer match in a fed state. Subjects completed six 15 min blocks (two halves of 45 min) of intermittent shuttle running, with a 15-min half-time. Blocks 3 and 6, allowed self-selection of running speeds and sprint times, were assessed throughout. Subjects consumed 250 mL of either a 12% carbohydrate solution (CHO) or a non-caloric taste matched placebo (PLA) before and at half-time of the LIST. Sprint times were not different between trials (CHO 2.71 ± 0.15 s, PLA 2.70 ± 0.14 s; p = 0.202). Total distance covered in self-selected blocks (block 3: CHO 2.07 ± 0.06 km; PLA 2.09 ± 0.08 km; block 6: CHO 2.04 ± 0.09 km; PLA 2.06 ± 0.08 km; p = 0.122) was not different between trials. There was no difference between trials for distance covered (p ≥ 0.297) or mean speed (p ≥ 0.172) for jogging or cruising. Blood glucose concentration was greater (p < 0.001) at the end of half-time during the CHO trial. In conclusion, consumption of 250 mL of 12% CHO solution before and at half-time of a simulated soccer match does not affect self-selected running or sprint performance in a fed state. PMID:28067762

Ecologically Valid Carbohydrate Intake during Soccer-Specific Exercise Does Not Affect Running Performance in a Fed State.

PubMed

Funnell, Mark P; Dykes, Nick R; Owen, Elliot J; Mears, Stephen A; Rollo, Ian; James, Lewis J

2017-01-05

This study assessed the effect of carbohydrate intake on self-selected soccer-specific running performance. Sixteen male soccer players (age 23 ± 4 years; body mass 76.9 ± 7.2 kg; predicted VO 2max = 54.2 ± 2.9 mL∙kg -1 ∙min -1 ; soccer experience 13 ± 4 years) completed a progressive multistage fitness test, familiarisation trial and two experimental trials, involving a modified version of the Loughborough Intermittent Shuttle Test (LIST) to simulate a soccer match in a fed state. Subjects completed six 15 min blocks (two halves of 45 min) of intermittent shuttle running, with a 15-min half-time. Blocks 3 and 6, allowed self-selection of running speeds and sprint times, were assessed throughout. Subjects consumed 250 mL of either a 12% carbohydrate solution (CHO) or a non-caloric taste matched placebo (PLA) before and at half-time of the LIST. Sprint times were not different between trials (CHO 2.71 ± 0.15 s, PLA 2.70 ± 0.14 s; p = 0.202). Total distance covered in self-selected blocks (block 3: CHO 2.07 ± 0.06 km; PLA 2.09 ± 0.08 km; block 6: CHO 2.04 ± 0.09 km; PLA 2.06 ± 0.08 km; p = 0.122) was not different between trials. There was no difference between trials for distance covered ( p ≥ 0.297) or mean speed ( p ≥ 0.172) for jogging or cruising. Blood glucose concentration was greater ( p < 0.001) at the end of half-time during the CHO trial. In conclusion, consumption of 250 mL of 12% CHO solution before and at half-time of a simulated soccer match does not affect self-selected running or sprint performance in a fed state.

The Decompression Sickness and Venous Gas Emboli Consequences of Air Breaks During 100% Oxygen Prebreathe

NASA Technical Reports Server (NTRS)

Conkin, J.; Gernhardt, M. L.; Powell, M. R.

2004-01-01

Not enough is known about the increased risk of hypobaric decompression sickness (DCS) and production of venous (VGE) and arterial (AGE) gas emboli following an air break in an otherwise normal 100% resting oxygen (O2) prebreathe (PB), and certainly a break in PB when exercise is used to accelerate nitrogen (N2) elimination from the tissues. Current Aeromedical Flight Rules at the Johnson Space Center about additional PB payback times are untested, possibly too conservative, and therefore not optimized for operational use. A 10 min air break at 90 min into a 120 min PB that includes initial dual-cycle ergometry for 10 min will show a measurable increase in the risk of DCS and VGE after ascent to 4.3 psia compared to a 10 min break at 15 min into the PB, or when there is no break in PB. Data collection with humans begins in 2005, but here we first evaluate the hypothesis using three models of tissue N2 kinetics: Model I is a simple single half-time compartment exponential model, Model II is a three compartment half-time exponential model, and Model III is a variable half-time compartment model where the percentage of maximum O2 consumption for the subject during dual-cycle ergometry exercise defines the half-time compartment. Model I with large rate constants to simulate an exercise effect always showed a late break in PB had the greatest consequence. Model II showed an early break had the greatest consequence. Model III showed there was no difference between early or late break in exercise PB. Only one of these outcomes will be observed when humans are tested. Our results will favor one of these models, and so advance our understanding of tissue N2 kinetics, and of altitude DCS after an air break in PB.

Dissociation kinetics of Fe(III)- and Al(III)-natural organic matter complexes at pH 6.0 and 8.0 and 25 °C

NASA Astrophysics Data System (ADS)

Jones, Adele M.; Pham, A. Ninh; Collins, Richard N.; Waite, T. David

2009-05-01

The rate at which iron- and aluminium-natural organic matter (NOM) complexes dissociate plays a critical role in the transport of these elements given the readiness with which they hydrolyse and precipitate. Despite this, there have only been a few reliable studies on the dissociation kinetics of these complexes suggesting half-times of some hours for the dissociation of Fe(III) and Al(III) from a strongly binding component of NOM. First-order dissociation rate constants are re-evaluated here at pH 6.0 and 8.0 and 25 °C using both cation exchange resin and competing ligand methods for Fe(III) and a cation exchange resin method only for Al(III) complexes. Both methods provide similar results at a particular pH with a two-ligand model accounting satisfactorily for the dissociation kinetics results obtained. For Fe(III), half-times on the order of 6-7 h were obtained for dissociation of the strong component and 4-5 min for dissociation of the weak component. For aluminium, the half-times were on the order of 1.5 h and 1-2 min for the strong and weak components, respectively. Overall, Fe(III) complexes with NOM are more stable than analogous complexes with Al(III), implying Fe(III) may be transported further from its source upon dilution and dispersion.

Influence of carbohydrate supplementation on skill performance during a soccer match simulation.

PubMed

Russell, Mark; Benton, David; Kingsley, Michael

2012-07-01

This study investigated the influence of carbohydrate supplementation on skill performance throughout exercise that replicates soccer match-play. Experimentation was conducted in a randomised, double-blind and cross-over study design. After familiarization, 15 professional academy soccer players completed a soccer match simulation incorporating passing, dribbling and shooting on two separate occasions. Participants received a 6% carbohydrate-electrolyte solution (CHO) or electrolyte solution (PL). Precision, success rate, ball speed and an overall index (speed-precision-success; SPS) were determined for all skills. Blood samples were taken at rest, immediately before exercise, every 15 min during exercise (first half: 15, 30 and 45 min; second half: 60, 75 and 90 min), and 10 min into the half time (half-time). Carbohydrate supplementation influenced shooting (time×treatment interaction: p<0.05), where CHO attenuated the decline in shot speed and SPS index. Supplementation did not affect passing or dribbling. Blood glucose responses to exercise were influenced by supplementation (time×treatment interaction: p<0.05), where concentrations were higher at 45 min and during half-time in CHO compared with PL. Blood glucose concentrations reduced by 30±1% between half-time and 60 min in CHO. Carbohydrate supplementation attenuated decrements in shooting performance during simulated soccer match-play; however, further research is warranted to optimise carbohydrate supplementation regimes for high-intensity intermittent sports. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Dissolution behaviour of 238U, 234U and 230Th deposited on filters from personal dosemeters.

PubMed

Becková, Vera; Malátová, Irena

2008-01-01

Kinetics of dissolution of (238)U, (234)U and (230)Th dust deposited on filters from personal alpha dosemeters was studied by means of a 26-d in vitro dissolution test with a serum ultrafiltrate simulant. Dosemeters had been used by miners at the uranium mine 'Dolní Rozínka' at Rozná, Czech Republic. The sampling flow-rate as declared by the producer is 4 l h(-1) and the sampling period is typically 1 month. Studied filters contained 125 +/- 6 mBq (238)U in equilibrium with (234)U and (230)Th; no (232)Th series nuclides were found. Half-time of rapid dissolution of 1.4 d for (238)U and (234)U and slow dissolution half-times of 173 and 116 d were found for (238)U and (234)U, respectively. No detectable dissolution of (230)Th was found.

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kosheverova, Vera V., E-mail: kosheverova_vera@incras.ru; Kamentseva, Rimma S., E-mail: rkamentseva@yandex.ru; St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time ofmore » slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.« less

Hypotensive effect of agmatine, arginine metabolite, is affected by NO synthase.

PubMed

Gerová, M; Török, J

2004-01-01

The metabolites of arginine were recently shown to be involved in cardiovascular control. The study addresses the general cardiovascular response of anaesthetized rats to agmatine, a decarboxylated arginine. The relation between two arginine metabolic pathways governed by arginine decarboxylase and nitric oxide synthase was investigated. Intravenous administration of agmatine 30 and 60 microM/0.1 ml saline elicited remarkable hypotension of 42.6+/-4.6 and 70.9+/-6.5 mm Hg, respectively. The hypotension was characterized by long duration with half-time of return 171.6+/-2.9 and 229.2+/-3.8 s, respectively. The time of total blood pressure BP recovery was about 10 min. Dose-dependent relaxation to agmatine was also found in aorta rings in vitro. Both doses of agmatine administered 60-180 min after NO synthase inhibition L-NAME 40 mg/kg i.v. caused greater hypotension 59.0+/-7.6 and 95.8 8.8 mm Hg P<0.01 both compared to animals with intact NO synthase, but this was accompanied by a significant shortening of the half-time of BP return. If agmatine was administered to hypertensive NO-deficient rats treated with 40 mg/kg/day L-NAME for 4 weeks, similar significant enhancement of hypotension was observed at both agmatine doses, again with a significant shortening of half-time of BP return. It can be summarized that the long-lasting hypotension elicited by agmatine was amplified after acute or chronic NO synthase inhibition, indicating a feedback relation between the two metabolic pathways of arginine.

The relationship between cadmium in kidney and cadmium in urine and blood in an environmentally exposed population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akerstrom, Magnus, E-mail: magnus.akerstrom@amm.gu.se; Barregard, Lars; Lundh, Thomas

Introduction: Cadmium (Cd) is toxic to the kidney and a major part of the body burden occurs here. Cd in urine (U-Cd) and blood (B-Cd) are widely-used biomarkers for assessing Cd exposure or body burden. However, empirical general population data on the relationship between Cd in kidney (K-Cd), urine, and blood are scarce. Our objectives were to determine the relationship between cadmium in kidney, urine, and blood, and calculate the elimination half-time of Cd from the kidney. Methods: Kidney cortex biopsies, urine, and blood samples were collected from 109 living kidney donors. Cd concentrations were determined and the relationships betweenmore » K-Cd, U-Cd, and B-Cd were investigated in regression models. The half-time of K-Cd was estimated from the elimination constant. Results: There was a strong association between K-Cd and U-Cd adjusted for creatinine (r{sub p} = 0.70, p < 0.001), while the association with B-Cd was weaker (r{sub p} = 0.44, p < 0.001). The relationship between K-Cd and U-Cd was nonlinear, with slower elimination of Cd at high K-Cd. Estimates of the K-Cd half-time varied between 18 and 44 years. A K-Cd of 25 μg/g corresponds to U-Cd of 0.42 μg/g creatinine in overnight urine (U-Cd/K-Cd ratio: about 1:60). Multivariate models showed Cd in blood and urinary albumin as determinants for U-Cd excretion. Discussion: In healthy individuals with low-level Cd exposure, there was a strong correlation between Cd in kidney and urine, especially after adjustment for creatinine. Urinary Cd was also affected by Cd in blood and urinary albumin. Previous estimates of the U-Cd/K-Cd ratio may underestimate K-Cd at low U-Cd. - Highlights: ► The first study of the relation between Cd in kidney, blood and urine at low U-Cd ► Simultaneous samples were collected from healthy kidney donors. ► There was a nonlinear relationship between cadmium in kidney and urine. ► Estimates of the kidney cadmium half-time were 18–44 years, depending on model used. ► Previous data seem to underestimate kidney cadmium at low urinary cadmium.« less

Tabun scavengers based on hydroxamic acid containing cyclodextrins.

PubMed

Brandhuber, Florian; Zengerle, Michael; Porwol, Luzian; Bierwisch, Anne; Koller, Marianne; Reiter, Georg; Worek, Franz; Kubik, Stefan

2013-04-28

Arrangement of several hydroxamic acid-derived substituents along the cavity of a cyclodextrin ring leads to compounds that detoxify tabun in TRIS-HCl buffer at physiological pH and 37.0 °C with half-times as low as 3 min.

34 CFR 686.25 - Correspondence study.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF EDUCATION (CONTINUED) TEACHER EDUCATION ASSISTANCE FOR COLLEGE AND HIGHER EDUCATION (TEACH... without terms, but not including any residential component, by— (1) Using the half-time annual award; and... correspondence courses using terms but not including any residential component— (1) The institution must prepare...

34 CFR 686.25 - Correspondence study.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., DEPARTMENT OF EDUCATION (CONTINUED) TEACHER EDUCATION ASSISTANCE FOR COLLEGE AND HIGHER EDUCATION (TEACH... without terms, but not including any residential component, by— (1) Using the half-time annual award; and... correspondence courses using terms but not including any residential component— (1) The institution must prepare...

34 CFR 686.25 - Correspondence study.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF EDUCATION (CONTINUED) TEACHER EDUCATION ASSISTANCE FOR COLLEGE AND HIGHER EDUCATION (TEACH... without terms, but not including any residential component, by— (1) Using the half-time annual award; and... correspondence courses using terms but not including any residential component— (1) The institution must prepare...

38 CFR 21.4236 - Tutorial assistance.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Programs of... educational program on a half-time or more basis at an educational institution, and (2) Has a deficiency in a...) Approval. The Department of Veterans Affairs will grant approval when: (1) The educational institution...

38 CFR 21.4236 - Tutorial assistance.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Programs of... educational program on a half-time or more basis at an educational institution, and (2) Has a deficiency in a...) Approval. The Department of Veterans Affairs will grant approval when: (1) The educational institution...

A review of lung-to-blood absorption rates for radon progeny.

PubMed

Marsh, J W; Bailey, M R

2013-12-01

The International Commission on Radiological Protection (ICRP) Publication 66 Human Respiratory Tract Model (HRTM) treats clearance of materials from the respiratory tract as a competitive process between absorption into blood and particle transport to the alimentary tract and lymphatics. The ICRP recommended default absorption rates for lead and polonium (Type M) in ICRP Publication 71 but stated that the values were not appropriate for short-lived radon progeny. This paper reviews and evaluates published data from volunteer and laboratory animal experiments to estimate the HRTM absorption parameter values for short-lived radon progeny. Animal studies showed that lead ions have two phases of absorption: ∼10 % absorbed with a half-time of ∼15 min, the rest with a half-time of ∼10 h. The studies also indicated that some of the lead ions were bound to respiratory tract components. Bound fractions, f(b), for lead were estimated from volunteer and animal studies and ranged from 0.2 to 0.8. Based on the evaluations of published data, the following HRTM absorption parameter values were derived for lead as a decay product of radon: f(r) = 0.1, s(r) = 100 d(-1), s(s) = 1.7 d(-1), f(b) = 0.5 and s(b) = 1.7 d(-1). Effective doses calculated assuming these absorption parameter values instead of a single absorption half-time of 10 h with no binding (as has generally been assumed) are only a few per cent higher. However, as there is some conflicting evidence on the absorption kinetics for radon progeny, dose calculations have been carried out for different sets of absorption parameter values derived from different studies. The results of these calculations are discussed.

A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

PubMed

Scott, B R; Dillehay, L E

1990-11-01

There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

Physiological and performance effects of carbohydrate gels consumed prior to the extra-time period of prolonged simulated soccer match-play.

PubMed

Harper, Liam D; Briggs, Marc A; McNamee, Ged; West, Daniel J; Kilduff, Liam P; Stevenson, Emma; Russell, Mark

2016-06-01

The physiological and performance effects of carbohydrate-electrolyte gels consumed before the 30min extra-time period of prolonged soccer-specific exercise were investigated. Randomised, double-blind, crossover. Eight English Premier League academy soccer players performed 120min of soccer-specific exercise on two occasions while consuming fluid-electrolyte beverages before exercise, at half-time and 90min. Carbohydrate-electrolyte (0.7±0.1gkg(-1) BM) or energy-free placebo gels were consumed ∼5min before extra-time. Blood samples were taken before exercise, at half-time and every 15min during exercise. Physical (15-m and 30-m sprint speed, 30-m sprint maintenance and countermovement jump height) and technical (soccer dribbling) performance was assessed throughout each trial. Carbohydrate-electrolyte gels improved dribbling precision (+29±20%) and raised blood glucose concentrations by 0.7±0.8mmoll(-1) during extra-time (both p<0.01). Supplementation did not affect sprint velocities (15m and 30m), 30-m sprint maintenance or dribbling speed as reductions compared to 0-15min values occurred at 105-120min irrespective of trial (all p<0.05). Plasma osmolality and blood sodium concentrations increased post-exercise vs. the opening 15min (p<0.05) but no effect of supplementation existed. Selected markers of physical performance (jump height, 30-m sprint velocity and 30-m repeated sprint maintenance) also reduced by >3% during half-time (all p<0.05). Carbohydrate-electrolyte gel ingestion raised blood glucose concentrations and improved dribbling performance during the extra-time period of simulated soccer match-play. Supplementation did not attenuate reductions in physical performance and hydration status that occurred during extra-time. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Progression of motor and nonmotor features of Parkinson's disease and their response to treatment

PubMed Central

Vu, Thuy C.; Nutt, John G.; Holford, Nicholas H. G.

2012-01-01

AIMS (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments. METHODS Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters. RESULTS Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2–3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED50 of 1237 mg day−1 compared with 7–24 mg day−1 for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression. CONCLUSIONS This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD. PMID:22283961

Early Detection of Ureteropelvic Junction Obstruction Using Signal Analysis and Machine Learning: A Dynamic Solution to a Dynamic Problem.

PubMed

Blum, Emily S; Porras, Antonio R; Biggs, Elijah; Tabrizi, Pooneh R; Sussman, Rachael D; Sprague, Bruce M; Shalaby-Rana, Eglal; Majd, Massoud; Pohl, Hans G; Linguraru, Marius George

2017-10-21

We sought to define features that describe the dynamic information in diuresis renograms for the early detection of clinically significant hydronephrosis caused by ureteropelvic junction obstruction. We studied the diuresis renogram of 55 patients with a mean ± SD age of 75 ± 66 days who had congenital hydronephrosis at initial presentation. Five patients had bilaterally affected kidneys for a total of 60 diuresis renograms. Surgery was performed on 35 kidneys. We extracted 45 features based on curve shape and wavelet analysis from the drainage curves recorded after furosemide administration. The optimal features were selected as the combination that maximized the ROC AUC obtained from a linear support vector machine classifier trained to classify patients as with or without obstruction. Using these optimal features we performed leave 1 out cross validation to estimate the accuracy, sensitivity and specificity of our framework. Results were compared to those obtained using post-diuresis drainage half-time and the percent of clearance after 30 minutes. Our framework had 93% accuracy, including 91% sensitivity and 96% specificity, to predict surgical cases. This was a significant improvement over the same accuracy of 82%, including 71% sensitivity and 96% specificity obtained from half-time and 30-minute clearance using the optimal thresholds of 24.57 minutes and 55.77%, respectively. Our machine learning framework significantly improved the diagnostic accuracy of clinically significant hydronephrosis compared to half-time and 30-minute clearance. This aids in the clinical decision making process by offering a tool for earlier detection of severe cases and it has the potential to reduce the number of diuresis renograms required for diagnosis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Nasal high flow clears anatomical dead space in upper airway models

PubMed Central

Celik, Gülnaz; Feng, Sheng; Bartenstein, Peter; Meyer, Gabriele; Eickelberg, Oliver; Schmid, Otmar; Tatkov, Stanislav

2015-01-01

Recent studies showed that nasal high flow (NHF) with or without supplemental oxygen can assist ventilation of patients with chronic respiratory and sleep disorders. The hypothesis of this study was to test whether NHF can clear dead space in two different models of the upper nasal airways. The first was a simple tube model consisting of a nozzle to simulate the nasal valve area, connected to a cylindrical tube to simulate the nasal cavity. The second was a more complex anatomically representative upper airway model, constructed from segmented CT-scan images of a healthy volunteer. After filling the models with tracer gases, NHF was delivered at rates of 15, 30, and 45 l/min. The tracer gas clearance was determined using dynamic infrared CO2 spectroscopy and 81mKr-gas radioactive gamma camera imaging. There was a similar tracer-gas clearance characteristic in the tube model and the upper airway model: clearance half-times were below 1.0 s and decreased with increasing NHF rates. For both models, the anterior compartments demonstrated faster clearance levels (half-times < 0.5 s) and the posterior sections showed slower clearance (half-times < 1.0 s). Both imaging methods showed similar flow-dependent tracer-gas clearance in the models. For the anatomically based model, there was complete tracer-gas removal from the nasal cavities within 1.0 s. The level of clearance in the nasal cavities increased by 1.8 ml/s for every 1.0 l/min increase in the rate of NHF. The study has demonstrated the fast-occurring clearance of nasal cavities by NHF therapy, which is capable of reducing of dead space rebreathing. PMID:25882385

University Advertising and Universality in Messaging

ERIC Educational Resources Information Center

Diel, Stan R.; Katsinas, Stephen

2018-01-01

University and college institutional advertisements, which typically are broadcast as public service announcements during the halftime of football games, were the subject of a quantitative analysis focused on commonality in messaging and employment of the semiotic theory of brand advertising. Findings indicate advertisements focus on students'…

5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS VOLUNTEER SERVICE § 308.101 Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited...

34 CFR 682.604 - Required exit counseling for borrowers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 4 2014-07-01 2014-07-01 false Required exit counseling for borrowers. 682.604 Section... counseling for borrowers. (a) Exit counseling. (1) A school must ensure that exit counseling is conducted... ensure that this counseling is conducted shortly before the student borrower ceases at least half-time...

Macrocytosis in Down Syndrome.

ERIC Educational Resources Information Center

Wachtel, Tom J.; Pueschel, Siegfried M.

1991-01-01

The study, with 61 Down Syndrome (trisomy 21) adult subjects, found that macrocytosis in the absence of anemia was virtually universal and erythrocyte survival half-time was shorter than normal. Findings suggest that erythrocytes have a younger mean age in persons with Down Syndrome, possibly indicating an accelerated aging process of red blood…

7 CFR 273.5 - Students.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 4 2013-01-01 2013-01-01 false Students. 273.5 Section 273.5 Agriculture Regulations... § 273.5 Students. (a) Applicability. An individual who is enrolled at least half-time in an institution... college or university that offers degree programs regardless of whether a high school diploma is required...

7 CFR 273.5 - Students.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 4 2012-01-01 2012-01-01 false Students. 273.5 Section 273.5 Agriculture Regulations... § 273.5 Students. (a) Applicability. An individual who is enrolled at least half-time in an institution... college or university that offers degree programs regardless of whether a high school diploma is required...

7 CFR 273.5 - Students.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 4 2014-01-01 2014-01-01 false Students. 273.5 Section 273.5 Agriculture Regulations... § 273.5 Students. (a) Applicability. An individual who is enrolled at least half-time in an institution... college or university that offers degree programs regardless of whether a high school diploma is required...

A Half-Time Mill School. Bulletin, 1919, No. 6

ERIC Educational Resources Information Center

Foght, H. W.

1919-01-01

Until a few years ago the Southern States were considered in the main an agricultural section. More recently the advantageous location in respect to raw materials, minerals, water, and electric power of the South Atlantic States has occasioned an almost unprecedented growth in manufacturing industries. Particularly has the cotton manufacturing…

Carbohydrates and Physical/Mental Performance during Intermittent Exercise to Fatigue.

ERIC Educational Resources Information Center

Welsh, Ralph S.; Davis, J. Mark; Burke, Jean R.; Williams, Harriet G.

2002-01-01

Investigated the effects of carbohydrate-electrolyte (CHO) ingestion on physical and mental function associated with performing high-intensity exercise. Physically active adults completed physical activities while researchers assessed them. CHO or placebo drinks were consumed before starting and at halftime. CHO ingestion resulted in 37 percent…

7 CFR 273.7 - Work provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ineligible to participate in the Food Stamp Program under paragraph (j) of this section. (viii) A student.... Students enrolled at least half-time in an institution of higher education must meet the student eligibility requirements listed in § 273.5. A student will remain exempt during normal periods of class...

7 CFR 273.7 - Work provisions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... ineligible to participate in the Food Stamp Program under paragraph (j) of this section. (viii) A student.... Students enrolled at least half-time in an institution of higher education must meet the student eligibility requirements listed in § 273.5. A student will remain exempt during normal periods of class...

7 CFR 273.7 - Work provisions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... ineligible to participate in the Food Stamp Program under paragraph (j) of this section. (viii) A student.... Students enrolled at least half-time in an institution of higher education must meet the student eligibility requirements listed in § 273.5. A student will remain exempt during normal periods of class...

7 CFR 273.7 - Work provisions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... ineligible to participate in the Food Stamp Program under paragraph (j) of this section. (viii) A student.... Students enrolled at least half-time in an institution of higher education must meet the student eligibility requirements listed in § 273.5. A student will remain exempt during normal periods of class...

7 CFR 273.7 - Work provisions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... ineligible to participate in the Food Stamp Program under paragraph (j) of this section. (viii) A student.... Students enrolled at least half-time in an institution of higher education must meet the student eligibility requirements listed in § 273.5. A student will remain exempt during normal periods of class...

5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited... interim between school years if the interim is not more than 5 months and if such individual shows to the...

5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited... interim between school years if the interim is not more than 5 months and if such individual shows to the...

5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited... interim between school years if the interim is not more than 5 months and if such individual shows to the...

5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited... interim between school years if the interim is not more than 5 months and if such individual shows to the...

38 CFR 21.4204 - Periodic certifications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... eligible persons. An eligible person enrolled in a course which leads to a standard college degree, excepting eligible persons pursuing the course on a less than half-time basis, must verify each month his or... standard college degree, if a school organized on a term, quarter, or semester basis has reported...

34 CFR 607.3 - What is an enrollment of needy students?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following programs: Pell Grant, Supplemental Educational Opportunity Grant, College Work-Study, and Perkins...-time basis and received Pell Grants exceeded the median percentage of undergraduate degree students who were enrolled on at least a half-time basis and received Pell Grants at comparable institutions that...

Human metabolism and ecological transfer of radioactive caesium: Comparative studies of Chernobyl debris and nuclear weapons fallout, in Southern Sweden and in Bryansk, Russia

NASA Astrophysics Data System (ADS)

Raaf, Christopher Leopold

The whole-body content of radiocaesium was measured in a South-Swedish urban group of people residing in the city of Lund (55.7°N, 13.2°E) between 1960 and 1994. The results from the survey have been analysed in order to estimate the ecological half-time, Teff,eco, of fallout radiocaesium and the aggregate transfer from ground deposition to man in the region. After 1987, the biological half-times, Ts, of 137Cs and 40K in man were also determined in the reference group through whole-body content measurements in combination with 24-hour urine sampling. Relationships between 24-hour urinary excretion and body burden of 137Cs in the group together with data from the literature were then applied to urine samples collected in 1994 and 1995 from adult subjects living in the highly contaminated region of Bryansk, Russia, in order to estimate their average body burden of 137Cs. The equivalent biological half-time for 137Cs in females of the Lund reference group was, on average (+/-1 WSE), 66 +/- 3 d, which agrees with other findings, whereas the value for the males, 81 +/- 4 d, was, on average, significantly lower than what is found in the literature. This is partly explained by the elevated mean age and relatively low mean body muscle mass of the males investigated in the group during the post-Chernobyl study period. The effective ecological half-time for 137Cs from Chernobyl was found to be 1.8 +/- 0.2 y. The aggregate transfer of 137Cs from deposition to mean activity concentration in man was estimated to be 1.7 Bq kg-1/kBq m-2. These vales may be compared with an effective ecological half-time of 1.3 years found in the reference group in the 1960s, and an aggregate transfer factor of 9.8 Bq kg-1/kBq m-2. The average committed effective dose from ingested 137Cs Chernobyl fallout in the study group was estimated to be 0.02 mSv and from the nuclear weapons fallout to 0.20 mSv. The estimates of whole-body content of 137Cs in the Russian subjects obtained through creatinine normalisation of the 137Cs content in urine were, on average, a factor of 2 higher than estimates obtained through a potassium normalisation procedure; 55 +/- 8 (1 SE) kBq for creatinine and 29 +/- 4 (1 SE) kBq for potassium normalisation in the year 1994. This was due to a significant difference in the relationship between the urinary potassium and creatinine concentration between the Swedish and Russian group. The elevated potassium concentration found in the rural Russian subjects indicated a higher dietary intake of potassium, which greatly influences the accuracy and applicability of the potassium normalisation method when estimating body burden of 137Cs through urine assay. It is therefore recommended not to use the potassium normalisation procedure in cases where the daily intake of potassium is unknown. The estimated body burden of 137Cs in the Bryansk group in 1994 corresponds to a contribution to the estimated annual effective dose of 1.8 mSv y-1, which is approximately 200 times greater than the average annual dose received from ingested 137Cs by the subjects of the Lund reference group during the period 1987-1994.

Coaches' Use of Anticipatory and Counterfactual Regret Messages during Competition

ERIC Educational Resources Information Center

Turman, Paul D.

2005-01-01

By focusing on coaches' use of anticipatory and counterfactual regret messages, this investigation examined video footage (i.e., pre-game, halftime, and post-game speeches) of high school football coaches' interaction with their athletes during competition. Participants were 17 high school football coaches who were found to use a combination of…

Central Synaptic Mechanisms Underlie Short-Term Olfactory Habituation in "Drosophila" Larvae

ERIC Educational Resources Information Center

Larkin, Aoife; Karak, Somdatta; Priya, Rashi; Das, Abhijit; Ayyub, Champakali; Ito, Kei; Rodrigues, Veronica; Ramaswami, Mani

2010-01-01

Naive "Drosophila" larvae show vigorous chemotaxis toward many odorants including ethyl acetate (EA). Chemotaxis toward EA is substantially reduced after a 5-min pre-exposure to the odorant and recovers with a half-time of [image omitted]20 min. An analogous behavioral decrement can be induced without odorant-receptor activation through…

25 CFR 20.315 - Who is not covered by the employment policy?

Code of Federal Regulations, 2014 CFR

2014-04-01

... ASSISTANCE AND SOCIAL SERVICES PROGRAMS Direct Assistance Employment Requirements § 20.315 Who is not covered... satisfactory progress. (c) A person enrolled at least half-time in a program of study under Section 5404 of Pub... Income (SSI) assistance A physician, psychologist, or social services worker certifies that a physical or...

25 CFR 20.315 - Who is not covered by the employment policy?

Code of Federal Regulations, 2012 CFR

2012-04-01

... ASSISTANCE AND SOCIAL SERVICES PROGRAMS Direct Assistance Employment Requirements § 20.315 Who is not covered... satisfactory progress. (c) A person enrolled at least half-time in a program of study under Section 5404 of Pub... Income (SSI) assistance A physician, psychologist, or social services worker certifies that a physical or...

25 CFR 20.315 - Who is not covered by the employment policy?

Code of Federal Regulations, 2013 CFR

2013-04-01

... ASSISTANCE AND SOCIAL SERVICES PROGRAMS Direct Assistance Employment Requirements § 20.315 Who is not covered... satisfactory progress. (c) A person enrolled at least half-time in a program of study under Section 5404 of Pub... Income (SSI) assistance A physician, psychologist, or social services worker certifies that a physical or...

Washington State Need Grant: Less-Than-Halftime Pilot Project (SHB 1345)

ERIC Educational Resources Information Center

Washington Higher Education Coordinating Board, 2006

2006-01-01

The 2005 Washington State Legislature authorized, through Substitute House Bill 1345, a two-year pilot project allowing eligible students, who enroll for four or five credits in a term, to receive the State Need Grant (SNG). Several important policy considerations emerged during the pilot project. Board staff explored these issues with financial…

5 CFR 213.3202 - Entire executive civil service.

Code of Federal Regulations, 2010 CFR

2010-01-01

... work experience acquired through a Federal work-study program while otherwise enrolled as a full-time... the Secretary of the U.S. Department of Education. The definition of half-time is the definition... may work full-time or part-time schedules at any time during the year. There are no limitations on the...

5 CFR 213.3202 - Entire executive civil service.

Code of Federal Regulations, 2012 CFR

2012-01-01

... work experience acquired through a Federal work-study program while otherwise enrolled as a full-time... the Secretary of the U.S. Department of Education. The definition of half-time is the definition... may work full-time or part-time schedules at any time during the year. There are no limitations on the...

Methods to improve routine bioassay monitoring for freshly separated, poorly transported plutonium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bihl, D.E.; Lynch, T.P.; Carbaugh, E.H.

1988-09-01

Several human cases involving inhalation of plutonium oxide at Hanford have shown clearance half-times from the lung that are much longer than the 500-day half-time recommended for class Y plutonium in Publication 30 of the International Commission on Radiological Protection(ICRP). The more tenaciously retained material is referred to as super class Y plutonium. The ability to detect super class Y plutonium by current routine bioassay measurements is shown to be poor. Pacific Northwest Laboratory staff involved in the Hanford Internal Dosimetry Program investigated four methods to se if improvements in routine monitoring of workers for fresh super class Y plutoniummore » are feasible. The methods were lung counting, urine sampling, fecal sampling, and use of diethylenetriaminepentaacetate (DTPA) to enhance urinary excretion. Use of DTPA was determined to be not feasible. Routine fecal sampling was found to be feasible but not recommended. Recommendations were made to improve the detection level for routine annual urinalysis and routine annual lung counting. 12 refs., 9 figs., 7 tabs.« less

Soccer-Specific Fatigue and Eccentric Hamstrings Muscle Strength

PubMed Central

Greig, Matt; Siegler, Jason C

2009-01-01

Context: Epidemiologic findings of higher incidences of hamstrings muscle strains during the latter stages of soccer match play have been attributed to fatigue. Objective: To investigate the influence of soccer-specific fatigue on the peak eccentric torque of the knee flexor muscles. Design: Descriptive laboratory study. Setting: Controlled laboratory environment. Patients or Other Participants: Ten male professional soccer players (age  =  24.7 ± 4.4 years, mass  =  77.1 ± 8.3 kg, V̇o2max  =  63.0 ± 4.8 mL·kg−1·min−1). Intervention(s): Participants completed an intermittent treadmill protocol replicating the activity profile of soccer match play, with a passive halftime interval. Before exercise and at 15-minute intervals, each player completed isokinetic dynamometer trials. Main Outcome Measure(s): Peak eccentric knee flexor torque was quantified at isokinetic speeds of 180° · s−1, 300° · s−1, and 60° · s−1, with 5 repetitions at each speed. Results: Peak eccentric knee flexor torque at the end of the game (T300eccH105  =  127 ± 25 Nm) and at the end of the passive halftime interval (T300eccH60  =  133 ± 32 Nm) was reduced relative to T300eccH00 (167 ± 35 Nm, P < .01) and T300eccH15 (161 ± 35 Nm, P  =  .02). Conclusions: Eccentric hamstrings strength decreased as a function of time and after the halftime interval. This finding indicates a greater risk of injuries at these specific times, especially for explosive movements, in accordance with epidemiologic observations. Incorporating eccentric knee flexor exercises into resistance training sessions that follow soccer-specific conditioning is warranted to try to reduce the incidence or recurrence of hamstrings strains. PMID:19295963

School Funding, At-Risk and All-Day Kindergarten and Performance. Special Report

ERIC Educational Resources Information Center

Kansas Association of School Boards, 2014

2014-01-01

Governor Sam Brownback has recommended the Kansas Legislature phase-in funding for full day kindergarten programs over the next five years. This proposal has also been adopted by the Kansas State Board of Education. Currently, all kindergarteners are counted as a half-time (0.5) student for funding purposes. About 87 percent of Kansas…

Time Out with Half-Time: Job Sharing in the Nineties.

ERIC Educational Resources Information Center

Turner, Linda

1996-01-01

Job sharing is a form of employment often overlooked by the average worker. Eight women were interviewed for this qualitative research study on the benefits and drawbacks of job sharing. Rather than simply allowing more time for them to spend with their children or on domestic chores, job sharing provided unanticipated opportunities to enjoy a…

Playing Indian at Halftime: The Controversy over American Indian Mascots, Logos, and Nicknames in School-Related Events

ERIC Educational Resources Information Center

Pewewardy, Cornel D.

2004-01-01

This article discusses the creation of stereotypical Indian mascots, how society reinforces and accepts those stereotypes, how negative stereotypes have affected the relationship between American Indians and the rest of society, and it suggests solutions educators might use to eliminate these mascots from school-related events. The intent of this…

The Emotional Uncertainties of Teaching: A Missing Link in Teacher Education.

ERIC Educational Resources Information Center

Winograd, Ken

The author conducted a self-study of his emotional experience as an elementary teacher. During a sabbatical from a position as an education professor in a teacher education department, he spent 1 year teaching half-time in a first-second-third grade blended classroom. Teacher emotions were located in a larger sociocultural context. The paper…

78 FR 23850 - Safety Zones; Annual Fireworks Events in the Captain of the Port Buffalo Zone

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-23

... Football Half time Fireworks and the Lorain Port Fest Fireworks are formatted differently than the other... zones. Likewise, this rule will amend the Browns Football Half time and the Lorain Port Fest safety.... (24) Browns Football Halftime Fireworks, Cleveland, OH. (i) Location. All U.S. waters of Cleveland...

38 CFR 21.9680 - Certifications and release of payments.

Code of Federal Regulations, 2010 CFR

2010-07-01

... individual is enrolled at a rate of pursuit greater than half-time; (C) The institution of higher learning at... an interval if— (A) The individual's rate of pursuit is one-half time or less on the last day of the...) Mortgage document; or (6) Current real property assessment; or (7) Voter registration card. (B) An...

Financial Implications of Half- and Full-Time Employment for Persons with Disabilities.

ERIC Educational Resources Information Center

Schloss, Patrick J.; And Others

1987-01-01

Balance sheets comparing yearly income and expenses were developed for three disabled worker situations: no earned income, half-time minimum-wage job, and full-time minimum-wage job. Net disposable income was comparable for part-time and full-time disabled workers, since eligibility for Medicaid, Food Stamps, and Supplemental Security Income was…

U.S. Military Deployments to Africa: Lessons from the Hunt for Joseph Kony and the Lord’s Resistance Army

DTIC Science & Technology

2014-08-01

decades has led to a thriving tourism sector. Beyond tourism , the economy is largely based on mining (copper, cobalt, gold, and limestone) and...gathered at sports bars throughout Kampala to watch the final game of the World Cup. During halftime, a suicide bomber destroyed the Ethiopia Village Club

Motor excitability measurements: the influence of gender, body mass index, age and temperature in healthy controls.

PubMed

Casanova, I; Diaz, A; Pinto, S; de Carvalho, M

2014-04-01

The technique of threshold tracking to test axonal excitability gives information about nodal and internodal ion channel function. We aimed to investigate variability of the motor excitability measurements in healthy controls, taking into account age, gender, body mass index (BMI) and small changes in skin temperature. We examined the left median nerve of 47 healthy controls using the automated threshold-tacking program, QTRAC. Statistical multiple regression analysis was applied to test relationship between nerve excitability measurements and subject variables. Comparisons between genders did not find any significant difference (P>0.2 for all comparisons). Multiple regression analysis showed that motor amplitude decreases with age and temperature, stimulus-response slope decreases with age and BMI, and that accommodation half-time decrease with age and temperature. The changes related to demographic features on TRONDE protocol parameters are small and less important than in conventional nerve conduction studies. Nonetheless, our results underscore the relevance of careful temperature control, and indicate that interpretation of stimulus-response slope and accommodation half-time should take into account age and BMI. In contrast, gender is not of major relevance to axonal threshold findings in motor nerves. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walton, B.T.; Maggart, E.F. Jr.

Cuticular and gastrointestinal penetration, in vivo metabolism, and excretion of (/sup 14/C)acridine were investigated in the nymphal cricket Acheta domesticus (L.) to find a pharmacodynamic basis for this insect's differential susceptibility to acridine at different life stages. Topically applied (/sup 14/C)acridine readily penetrated the cuticular exoskeleton of nymphs (half-time of penetration, 48 min). Radiolabeled compounds appeared in the hemolymph within 0.5 h after ingestion of (/sup 14/C)acridine and continued to move across the gut wall for 7.5 h. The biological half-time was 18 h and the rate constant for elimination was 0.039 h/sup -1/ after ingestion. Within 5 d aftermore » dosing, 97% of the dose was excreted. Several metabolites were present in the feces of nymphs fed (/sup 14/C)acridine, and less than 13% of the extractable radioactivity was parent compound. The cuticule and the gastrointestinal tract proved to be ineffective barriers to acridine entry in A. domesticus. However, the ability to readily metabolize and excrete acridine probably contributes to the higher acridine tolerance observed in the nymphs and adults than in the eggs, which are susceptible to toxic effects. Acridine is found in many coal and synthetic fuel by-products.« less

Oxytocin binding sites in bovine mammary tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Xin.

1989-01-01

Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressinmore » binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.« less

Microanalysis and preliminary pharmacokinetic studies of a sulfated polysaccharide from Laminaria japonica

NASA Astrophysics Data System (ADS)

Zhang, Wenjing; Sun, Delin; Zhao, Xia; Jin, Weihua; Wang, Jing; Zhang, Quanbin

2016-01-01

A rapid, sensitive and reproducible high performance liquid chromatography (HPLC) method with post-column fluorescence derivatization has been developed to determine the amount of low-molecular-weight sulfated polysaccharide (GFS) in vivo. The metabolism of GFS has been shown to fit a two component model following its administration by intravenous injection, and its pharmacokinetic parameters were determined to be as follows: half-time of distribution phase ( t 1/2α)=11.24±2.93 min, half-time of elimination phase ( t 1/2β)=98.20±25.78 min, maximum concentration ( C max)=110.53 μg/mL and peak time ( T max)=5 min. The pharmacokinetic behavior of GFS was also investigated following intragastric administration. However, the concentration of GFS found in serum was too low for detection, and GFS could only be detected for up to 2 h after intragastric administration (200 mg/kg body weight). Thus, the bioavailability of GFS was low following intragastric administration because of the metabolism of GFS. In conclusion, HPLC with postcolumn derivatization could be used for quantitative microanalysis and pharmacokinetic studies to determine the presence of polysaccharides in the serum following intravenous injection.

Problems with detection of intakes of very insoluble plutonium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bihl, D.E.; Lynch, T.P.; Carbaugh, E.H.

1988-08-01

Several human cases involving inhalation of plutonium oxide at Hanford have shown clearance half-times from the lung that are much longer than those recommended for class Y material in Publication 30 of the International Commission on Radiological Protection (ICRP 1979). Because the material is much more tenaciously retained in the lung than ''normal'' class Y material, the Hanford Internal Dosimetry Program has been referring to it as ''super'' class Y. This material poses some major challenges with regard to the design and operation of bioassay monitoring programs. Because of the relative completeness of their data, 10 cases that show lungmore » retention half-times in excess of 5000 days are of particular interest. However, the bioassay data for these cases span the past 30 years and involve various sampling methods and detection limits in vogue at the time. Furthermore, the data were collected for the purpose of determining compliance with regulations in place at the time, rather than for research or modeling of clearance pathways and rates. So from a modeling perspective, the data have gaps, but are sufficiently complete to be convincing. 3 refs., 2 figs., 2 tabs.« less

Long-term follow-up of HAN-1, an acute plutonium oxide inhalation case

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carbaugh, E.H.; Bihl, D.E.; Sula, M.J.

1990-06-01

The International Commission on Radiation Protection (ICRP) has recommended that plutonium oxide be designated an inhalation class Y material, indicating that a 500-day clearance half-time from the lung is adequate for radiation protection purposes. Based on extensive data obtained from one particular inhalation case (referred to here as HAN-1), and supported by somewhat less detailed data in nine other cases, an argument has been put forth that substantially longer clearance half-times may not be uncommon for Pu oxide. This has led to the tentative identification of a super class Y'' form of Pu which has been factored into worker monitoringmore » programs at the US Department of Energy's Hanford Site. In addition, the United States Transuranium Registry autopsy work has indicted evidence to support the super class Y case. The particular case described in this paper was the key case which caused the Hanford internal dosimetry staff to seriously consider super class Y material. This paper includes data from long-term follow up monitoring as well as early data for calculating intakes for comparisons with secondary limits. 13 refs, 2 figs., 1 tab.« less

Impact of variations in the chemical composition of vitreous mineral fibers on biopersistence in rat lungs and consequences for regulation.

PubMed

Bellmann, Bernd; Schaeffer, Helmut A; Muhle, Hartwig

2010-08-01

The chronic toxicity of vitreous fibers is substantially dependent on their biopersistence. Removal of fibers deposited in the respiratory tract is dependent on a combination of physiological clearance processes (like mechanical translocation) and physico-chemical processes like dissolution and leaching. This publication presents data of about 60 different fibers investigated in the biopersistence test which was standardized in the European Union. This test is based on in vivo investigation of biopersistence after intratracheal instillation in rats of a respirable fiber fraction, and it is a basis for the regulatory classification of vitreous fibers. Regression analysis is carried out employing the data of glass fiber compositions and the corresponding results of biopersistence tests (half-times). The study leads to a model that enables prediction of half-times for stone wool fibers as well as for glass wool fibers on the basis of their chemical composition. The aim of this paper was to investigate the stringency of the existing limits for the range of the chemical composition of glass and stone wools in view of the currently available data base. For regulatory purposes, however, this model is currently not sufficient to replace biopersistence tests completely.

Rejoining and misrejoining of radiation-induced chromatin breaks. III. Hypertonic treatment

NASA Technical Reports Server (NTRS)

Durante, M.; George, K.; Wu, H. L.; Yang, T. C.

1998-01-01

It has been shown that treatment in anisotonic medium modifies rejoining of radiation-induced breaks in interphase chromosomes. In previous work, we have demonstrated that formation of exchanges in human lymphocytes has a slow component (half-time of 1-2 h), but a fraction of exchanges are also observed in samples assayed soon after exposure. In this paper we studied the effect of hypertonic treatment on rejoining and misrejoining of radiation-induced breaks using fluorescence in situ hybridization of prematurely condensed chromosomes in human lymphocytes. Isolated lymphocytes were irradiated with 7 Gy gamma rays, fused to mitotic hamster cells and incubated in hypertonic solution (0.5 M NaCl) for the period normally allowed for interphase chromosome condensation to occur. The data from hypertonic treatment experiments indicate the presence of a class of interphase chromosome breaks that rejoin and misrejoin very quickly (half-time of 5-6 min). The fast misrejoining of these lesions is considered to be responsible for the initial level of exchanges which we reported previously. No significant effect of hypertonic treatment on the yield of chromosome aberrations scored at the first postirradiation mitosis was detected.

Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

PubMed

Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

2015-06-01

Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheppard, S.C.; Evenden, W.G.; Cornwell, T.C.

The relative depuration and uptake kinetics of contaminants should be known to interpret appropriately the use of organisms such as earthworms in environmental bioassays and monitoring. For example, 14-d earthworm bioassays should be interpreted with the knowledge that some contaminants will continue to accumulate in tissues for months. The radiotracers {sup 125}I, {sup 134}Cs, {sup 54}Mn, {sup 65}Zn, and {sup 109}Cd were applied to deciduous litter and specimens of Lumbricus terrestris were exposed, either to litter alone or to litter on the top of soil columns. Depuration was monitored for 120 d and uptake, in a separate experiment, for 20more » d. Both depuration and uptake were described using two-phase, first-order statistical models. Cut clearance had a mean half-time of 1.4 d. The mean half-time for physiological depuration decreased from I (210 d) > Cd (150 d) > Zn (69 d) > Mn (40 d) > Cs (24 d). Both the depuration and the uptake experiments were necessary to resolve even partially the multiphase processes. Earthworm/soil dry weight concentration ratios decreased from Cd > Zn > I {ge} Cs {ge} Mn. The very slow kinetics indicate that tissue concentrations will increase continuously for a long time, with important implications for subsequent food-chain transfers.« less

Rates of cuticular penetration of chelated Fe(III): role of humidity, concentration, adjuvants, temperature, and type of chelate.

PubMed

Schönherr, Jörg; Fernández, Victoria; Schreiber, Lukas

2005-06-01

Time courses of cuticular penetration of FeCl3 and Fe(III) complexes of citric acid, EDTA, EDDHA (Sequestrene 138Fe), imidodisuccinic acid (IDHA), and ligninsulfonic acid (Natrel) were studied using astomatous cuticular membranes (CMs) isolated from Populus x canescens leaves. At 100% relative humidity, the Fe(III) chelates disappeared exponentially with time from the surface of the CMs; that is, penetration was a first-order process that can be described using rate constants or half-times of penetration (t(1/2)). Half-times ranged from 20 to 30 h. At 90% humidity, penetration rates were insignificant with the exception of Natrel, for which t(1/2) amounted to 58 h. Rate constants were independent of temperature (15, 25, and 35 degrees C). Permeability decreased with increasing Fe chelate concentration (IDHA and EDTA). At 100% humidity, half-times measured with FeIDHA were 11 h (2 mmol L(-1)), 17 h (10 mmol L(-1)) and 36 h (20 mmol L(-1)), respectively. In the presence of FeEDTA, penetration of CaCl2 was slowed greatly. Half-times for penetration of CaCl2, which were 1.9 h in the absence of FeEDTA, rose to 3.12 h in the presence of an equimolar concentration of EDTA and 13.3 h when the FeEDTA concentration was doubled. Hence, Fe chelates reduced permeability of CMs to CaCl2 and to the Fe chelates themselves. It is suggested that Fe chelates reduced the size of aqueous pores. This view is supported by the fact that rate constants for calcium salts were about 5 times higher than for Fe chelates with the same molecular weights. Adding Tween 20 (5 g L(-1)) as a humectant did not increase permeability to FeIDHA at 90% humidity and below, while addition of glycine betaine did. Penetration of FeCl3 applied at 5 g L(-1) (pH 1.5) was not a first order process as rate constants decreased rapidly with time. Only 2% of the dose penetrated during the first 2 h and less than that in the subsequent 8 h. Recovery was only 70%. This was attributed to the formation of insoluble Fe hydroxide precipitates on CMs. These results explain why in the past foliar application of Fe compounds had limited success. Inorganic Fe salts are instable and phytotoxic because of low pH, while Fe chelates penetrate slowly and 100% humidity is required for significant penetration rates. Concentrations as low as reasonably possible should be used. These physical facts are expected to apply to stomatous leaf surfaces as well, but absolute rates probably depend on leaf age and plant species. High humidity in stagnant air layers may favor penetration rates across stomatous leaf surfaces when humidity in bulk air is below 100%.

Preparing for the Worst-Case Scenario--Planning Pays Off with First-Ever Stadium Evacuation

ERIC Educational Resources Information Center

Bradley, Carol C.

2012-01-01

It's Saturday, September 3, Notre Dame vs. South Florida--the first home game of the season--and nearing halftime. The only person feeling more pressure than Head Coach Brian Kelly is Mike Seamon, associate vice president for campus safety and director of game day operations. Bad weather is on the way, and he's about to make the call to evacuate…

Learning Loops--Interactions between Guided Reflection and Experience-Based Learning in a Serious Game Activity

ERIC Educational Resources Information Center

Cowley, B.; Heikura, T.; Ravaja, N.

2013-01-01

In a study on experience-based learning in serious games, 45 players were tested for topic comprehension by a questionnaire administered before and after playing the single-player serious game Peacemaker (Impact Games 2007). Players were divided into two activity conditions: 20 played a 1-h game with a 3-min half-time break to complete an affect…

Reinforcers of the Occupation of Homemaker: An Analysis of the Need-Gratifying Properties of the Homemaker Occupation across the Stages of the Homemaker Life Cycle.

ERIC Educational Resources Information Center

Tinsley, Howard E. A.; Tinsley, Diane J.

1989-01-01

Examined the pattern of reinforcers characteristic of the homemaker occupation in order to identify occupations similar and dissimilar to this job. Homemakers (N=107) with less than half-time employment completed the Minnesota Job Description Questionnaire (MJDQ). Reinforcers for homemaking role include decision-making authority and autonomy,…

Primate polonium metabolic models and their use in estimation of systemic radiation doses from bioassay data. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, N.

1989-03-15

A Polonium metabolic model was derived and incorporated into a Fortran algorithm which estimates the systemic radiation dose from {sup 210}Po when applied to occupational urine bioassay data. The significance of the doses estimated are examined by defining the degree of uncertainty attached to them through comprehensive statistical testing procedures. Many parameters necessary for dosimetry calculations (such as organ partition coefficients and excretion fractions), were evaluated from metabolic studies of {sup 210}Po in non-human primates. Two tamarins and six baboons were injected intravenously with {sup 210}Po citrate. Excreta and blood samples were collected. Five of the baboons were sacrificed atmore » times ranging from 1 day to 3 months post exposure. Complete necropsies were performed and all excreta and the majority of all skeletal and tissue samples were analyzed radiochemically for their {sup 210}Po content. The {sup 210}Po excretion rate in the baboon was more rapid than in the tamarin. The biological half-time of {sup 210}Po excretion in the baboon was approximately 15 days while in the tamarin, the {sup 210}Po excretion rate was in close agreement with the 50 day biological half-time predicted by ICRP 30. Excretion fractions of {sup 210}Po in the non-human primates were found to be markedly different from data reported elsewhere in other species, including man. A thorough review of the Po urinalysis procedure showed that significant recovery losses resulted when metabolized {sup 210}Po was deposited out of raw urine. Polonium-210 was found throughout the soft tissues of the baboon but not with the partition coefficients for liver, kidneys, and spleen that are predicted by the ICRP 30 metabolic model. A fractional distribution of 0.29 for liver, 0.07 for kidneys, and 0.006 for spleen was determined. Retention times for {sup 210}Po in tissues are described by single exponential functions with biological half-times ranging from 15 to 50 days.« less

Carbohydrate ingestion before and during soccer match play and blood glucose and lactate concentrations.

PubMed

Russell, Mark; Benton, David; Kingsley, Michael

2014-01-01

The ingestion of carbohydrate (CHO) before and during exercise and at halftime is commonly recommended to soccer players for maintaining blood glucose concentrations throughout match play. However, an exercise-induced rebound glycemic response has been observed in the early stages of the second half of simulated soccer-specific exercise when CHO-electrolyte beverages were consumed regularly. Therefore, the metabolic effects of CHO beverage consumption throughout soccer match play remain unclear. To investigate the blood glucose and blood lactate responses to CHOs ingested before and during soccer match play. Crossover study. Applied research study. Ten male outfield academy soccer players (age = 15.6 ± 0.2 years, height = 1.74 ± 0.02 m, mass = 65.3 ± 1.9 kg, estimated maximal oxygen consumption = 58.4 ± 0.8 mL·kg(-1)·min(-1)). Players received a 6% CHO-electrolyte solution or an electrolyte (placebo) solution 2 hours before kickoff, before each half (within 10 minutes), and every 15 minutes throughout exercise. Blood samples were obtained at rest, every 15 minutes during the match (first half: 0-15, 15-30, and 30-45 minutes; second half: 45-60, 60-75, and 75-90 minutes) and 10 minutes into the halftime break. Metabolic responses (blood glucose and blood lactate concentrations) and markers of exercise intensity (heart rate) were recorded. Supplementation influenced the blood glucose response to exercise (time × treatment interaction effect: P ≤ .05), such that glucose concentrations were higher at 30 to 45 minutes in the CHO than in the placebo condition. However, in the second half, blood glucose concentrations were similar between conditions because of transient reductions from peak values occurring in both trials at halftime. Blood lactate concentrations were elevated above those at rest in the first 15 minutes of exercise (time-of-sample effect: P < .001) and remained elevated throughout exercise. Supplementation did not influence the pattern of response (time × treatment interaction effect: P = .49). Ingestion of a 6% CHO-electrolyte beverage before and during soccer match play did not benefit blood glucose concentrations throughout the second half of exercise.

Kinetics and dosimetry of thallium-201 in human testes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, D.V.; Shepstone, B.J.; Wilkins, H.B.

Thallous chloride ({sup 201}Tl) is a well-known imaging agent. It has been shown to accumulate in the testes. In view of this, the testicular kinetics of {sup 201}Tl is investigated in humans and the absorbed dose to the organ calculated. Thallous chloride {sup 201}Tl was injected intravenously into four patients for myocardial perfusion studies. After clinical evaluation, the testicular uptake and clearance of {sup 201}Tl were monitored for about 1 wk using a gamma camera. Testicular uptake of {sup 201}Tl was rapid with a mean biological uptake half-time of 0.67 hr and mean biological clearance half-time of 280 hr. Themore » mean maximum testicular uptake of {sup 201}Tl was about 0.4% of the injected activity. These data were utilized to calculate the average absorbed dose to the testes. The absorbed dose to the testes was calculated to be 3.5 x 10{sup {minus}4} Gy/MBq (1.3 rad/mCi) of injected activity. When the relative biological effectiveness of the Auger emitter {sup 201}Tl is taken into account, the equivalent dose to the testes is 9.5 x 10{sup {minus}4} Sv/MBq (3.5 rem/mCi). 14 refs., 1 fig., 2 tabs.« less

High polarization of nuclear spins mediated by nanoparticles at millikelvin temperatures.

PubMed

Owers-Bradley, John R; Horsewill, Anthony J; Peat, David T; Goh, Kelvin S K; Gadian, David G

2013-07-07

Nuclear magnetic resonance (NMR) techniques are extensively used in many areas of basic and clinical research, as well as in diagnostic medicine. However, NMR signals are intrinsically weak, and this imposes substantial constraints on the amounts and concentrations of materials that can be detected. The signals are weak because of the low energies characteristic of NMR and the resulting very low (typically 0.0001-0.01%) polarization of the nuclear spins. Here, we show that exposure to very low temperatures and high magnetic fields, in conjunction with nanoparticle-mediated relaxation enhancement, can be used to generate extremely high nuclear polarization levels on a realistic timescale; with copper nanoparticles at 15 mK and 14 T, (13)C polarization grew towards its equilibrium level of 23% with an estimated half-time of about 60 hours. This contrasts with a (13)C half-time of at least one year in the presence of aluminium nanoparticles. Cupric oxide nanoparticles were also effective relaxation agents. Our findings lead us to suspect that the relaxation may be mediated, at least in part, by the remarkable magnetic properties that some nanoparticle preparations can display. This methodology offers prospects for achieving polarization levels of 10-50% or more for many nuclear species, with a wide range of potential applications in structural biology and medicine.

Is team confidence the key to success? The reciprocal relation between collective efficacy, team outcome confidence, and perceptions of team performance during soccer games.

PubMed

Fransen, Katrien; Decroos, Steven; Vanbeselaere, Norbert; Vande Broek, Gert; De Cuyper, Bert; Vanroy, Jari; Boen, Filip

2015-01-01

The present manuscript extends previous research on the reciprocal relation between team confidence and perceived team performance in two ways. First, we distinguished between two types of team confidence; process-oriented collective efficacy and outcome-oriented team outcome confidence. Second, we assessed both types not only before and after the game, but for the first time also during half-time, thereby providing deeper insight into their dynamic relation with perceived team performance. Two field studies were conducted, each with 10 male soccer teams (N = 134 in Study 1; N = 125 in Study 2). Our findings provide partial support for the reciprocal relation between players' team confidence (both collective efficacy and team outcome confidence) and players' perceptions of the team's performance. Although both types of players' team confidence before the game were not significantly related to perceived team performance in the first half, players' team confidence during half-time was positively related to perceived team performance in the second half. Additionally, our findings consistently demonstrated a relation between perceived team performance and players' subsequent team confidence. Considering that team confidence is a dynamical process, which can be affected by coaches and players, our findings open new avenues to optimise team performance.

Effect of dark pretreatment on the kinetics of response of barley pulvini to gravistimulation and hormones

NASA Technical Reports Server (NTRS)

Brock, T. G.; Kaufman, P. B.

1988-01-01

Starch in pulvinus amyloplasts of barley (Hordeum vulgare cv Larker) disappears when 45-day-old, light-grown plants are given 5 days of continuous darkness. The effect of this loss on the pulvinus graviresponse was evaluated by following changes in the kinetics of response during the 5-day dark period. Over 5 days of dark pretreatment, the lag to initial graviresponse and the subsequent half-time to maximum steady state bending rate increased significantly while the maximum bending rate did not change. The change in response to applied indoleacetic acid (100 micromolar) plus gibberellic acid (10 micromolar) without gravistimulation, under identical dark pretreatments, was used as a model system for the response component of gravitropism. Dark pretreatment did not change the lag to initial response following hormone application to vertical pulvini, but both the maximum bending rate and the half-time to the maximum rate were significantly reduced. Also, after dark pretreatment, significant bending responses following hormone application were observed in vertical segments with or without added sucrose, while gravistimulation produced a response only if segments were given sucrose. These results indicate that starch-filled amyloplasts are required for the graviresponse of barley pulvini and suggest that they function in the stimulus perception and signal transduction components of gravitropism.

Carbohydrate Ingestion Before and During Soccer Match Play and Blood Glucose and Lactate Concentrations

PubMed Central

Russell, Mark; Benton, David; Kingsley, Michael

2014-01-01

Context: The ingestion of carbohydrate (CHO) before and during exercise and at halftime is commonly recommended to soccer players for maintaining blood glucose concentrations throughout match play. However, an exercise-induced rebound glycemic response has been observed in the early stages of the second half of simulated soccer-specific exercise when CHO-electrolyte beverages were consumed regularly. Therefore, the metabolic effects of CHO beverage consumption throughout soccer match play remain unclear. Objective: To investigate the blood glucose and blood lactate responses to CHOs ingested before and during soccer match play. Design: Crossover study. Setting: Applied research study. Patients or Other Participants: Ten male outfield academy soccer players (age = 15.6 ± 0.2 years, height = 1.74 ± 0.02 m, mass = 65.3 ± 1.9 kg, estimated maximal oxygen consumption = 58.4 ± 0.8 mL·kg−1·min−1). Intervention(s): Players received a 6% CHO-electrolyte solution or an electrolyte (placebo) solution 2 hours before kickoff, before each half (within 10 minutes), and every 15 minutes throughout exercise. Blood samples were obtained at rest, every 15 minutes during the match (first half: 0–15, 15–30, and 30–45 minutes; second half: 45–60, 60–75, and 75–90 minutes) and 10 minutes into the halftime break. Main Outcome Measure(s): Metabolic responses (blood glucose and blood lactate concentrations) and markers of exercise intensity (heart rate) were recorded. Results: Supplementation influenced the blood glucose response to exercise (time × treatment interaction effect: P ≤ .05), such that glucose concentrations were higher at 30 to 45 minutes in the CHO than in the placebo condition. However, in the second half, blood glucose concentrations were similar between conditions because of transient reductions from peak values occurring in both trials at halftime. Blood lactate concentrations were elevated above those at rest in the first 15 minutes of exercise (time-of-sample effect: P < .001) and remained elevated throughout exercise. Supplementation did not influence the pattern of response (time × treatment interaction effect: P = .49). Conclusions: Ingestion of a 6% CHO-electrolyte beverage before and during soccer match play did not benefit blood glucose concentrations throughout the second half of exercise. PMID:24933430

In vitro methane and gas production with inocula from cows and goats fed an identical diet.

PubMed

Mengistu, Genet; Hendriks, Wouter H; Pellikaan, Wilbert F

2018-03-01

Fermentative capacity among ruminants can differ depending on the type of ruminant species and the substrate fermented. The aim was to compare in vitro cow and goat rumen inocula in terms of methane (CH 4 ) and gas production (GP), fermentation kinetics and 72 h volatile fatty acids (VFA) production using the browse species Acacia etbaica, Capparis tomentosa, Dichrostachys cinerea, Rhus natalensis, freeze-dried maize silage and grass silage, and a concentrate as substrates. Total GP, CH 4 and VFA were higher (P ≤ 0.008) in goat inoculum than cows across substrates. The half-time for asymptotic GP was lower (P < 0.0001) in phase 1 and higher (P < 0.012) in phase 2, and the maximum rate of GP was higher (P < 0.0001) in phase 1 and phase 3 (P < 0.0001) in goats compared to cows. Methane production and as a percentage of total GP was higher (P < 0.0001) and the half-time tended (P = 0.059) to be at a later time for goats compared to cows. Goat inoculum showed higher fermentative activity with a concomitant higher CH 4 production compared to cows. This difference highlights the ability of goats to better utilise browse species and other roughage types. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Preparation and in-vitro/in-vivo evaluation of curcumin nanosuspension with solubility enhancement.

PubMed

Li, Xin; Yuan, Huiling; Zhang, Caiyun; Chen, Weidong; Cheng, Weiye; Chen, Xin; Ye, Xi

2016-08-01

We developed Cur nanosuspension (Cur-NS) with PVPK30 and SDS as stabilizers to improve poor water solubility and short biological half-time of Cur. Physicochemical characterization of Cur-NS was characterized systematically. The in-vitro dissolution, cytotoxicity and in-vivo pharmacokinetic experiments of Cur-NS were also evaluated. Scanning electron microscope indicated that the morphologies of Cur-NS were spherical or ellipsoidal in shape. X-ray diffraction verified that Cur was successfully developed as nanoparticles with an amorphous phase in Cur-NS. Fourier transform infrared spectroscopy suggested there was no degradation about Cur in the Cur-NS. Furthermore, the in-vitro study showed that the cumulative release of the Cur-NS was 82.16 ± 2.62% within 34 h and the cytotoxicity of the Cur-NS against HepG2 cells was much better than raw Cur. Besides, in-vivo pharmacokinetics in rats by intravenous injection displayed that the in-vivo process of Cur-NS pertained to two-compartment model. Meanwhile, the t1/2 and AUC0-t of Cur-NS were enhanced by 11.0-fold and 4.2-fold comparing to Cur solution. The Cur-NS significantly increased the water solubility and half-time of Cur, suggesting its potential as a nanocarrier in the delivery of Cur for future clinical application. © 2016 Royal Pharmaceutical Society.

First In Vivo Evaluation of Liposome-encapsulated 223Ra as a Potential Alpha-particle-emitting Cancer Therapeutic Agent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jonasdottir, Thora J.; Fisher, Darrell R.; Borrebaek, Jorgen

2006-09-13

Liposomes carrying chemotherapeutics have had some success in cancer treatment and may be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution of and to estimate the radiation doses from the alpha emitter 223Ra loaded into pegylated liposomes in selected tissues. 223Ra was encapsulated in pegylated liposomal doxorubicin by ionophore-mediated loading. The biodistribution of liposomal 223Ra was compared to free cationic 223Ra in Balb/C mice. We showed that liposomal 223 Ra circulated in the blood with an initial half-time in excess of 24 hours, which agreed well with that reported for liposomal doxorubicin in rodents, whilemore » the blood half-time of cationic 223Ra was considerably less than one hour. When liposomal 223 Ra was catabolized, the released 223Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free 223Ra. Pre-treatment with non-radioactive liposomal doxorubicin 4 days in advance lessened the liver uptake of liposomal 223 Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses. Liposomal 223 Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.« less

Kinetics of nucleation and crystallization in poly(e-caprolactone) (PCL)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhuravlev, Evgeny; Schmelzer, Jurn; Wunderlich, Bernhard

2011-01-01

The recently developed differential fast scanning calorimetry (DFSC) is used for a new look at the crystal growth of poly(3-caprolactone) (PCL) from 185 K, below the glass transition temperature, to 330 K, close to the equilibrium melting temperature. The DFSC allows temperature control of the sample and determination of its heat capacity using heating rates from 50 to 50,000 K/s. The crystal nucleation and crystallization halftimes were determined simultaneously. The obtained halftimes cover a range from 3 102 s (nucleation at 215 K) to 3 109 s (crystallization at 185 K). After attempting to analyze the experiments with the classicalmore » nucleation and growth model, developed for systems consisting of small molecules, a new methodology is described which addresses the specific problems of crystallization of flexible linear macromolecules. The key problems which are attempted to be resolved concern the differences between the structures of the various entities identified and their specific role in the mechanism of growth. The structures range from configurations having practically unmeasurable latent heats of ordering (nuclei) to being clearly-recognizable, ordered species with rather sharp disordering endotherms in the temperature range from the glass transition to equilibrium melting for increasingly perfect and larger crystals. The mechanisms and kinetics of growth involve also a detailed understanding of the interaction with the surrounding rigid-amorphous fraction (RAF) in dependence of crystal size and perfection.« less

Diffusion of small molecules into medaka embryos improved by electroporation

PubMed Central

2013-01-01

Background Diffusion of small molecules into fish embryos is essential for many experimental procedures in developmental biology and toxicology. Since we observed a weak uptake of lithium into medaka eggs we started a detailed analysis of its diffusion properties using small fluorescent molecules. Results Contrary to our expectations, not the rigid outer chorion but instead membrane systems surrounding the embryo/yolk turned out to be the limiting factor for diffusion into medaka eggs. The consequence is a bi-phasic uptake of small molecules first reaching the pervitelline space with a diffusion half-time in the range of a few minutes. This is followed by a slow second phase (half-time in the range of several hours) during which accumulation in the embryo/yolk takes place. Treatment with detergents improved the uptake, but strongly affected the internal distribution of the molecules. Testing electroporation we could establish conditions to overcome the diffusion barrier. Applying this method to lithium chloride we observed anterior truncations in medaka embryos in agreement with its proposed activation of Wnt signalling. Conclusions The diffusion of small molecules into medaka embryos is slow, caused by membrane systems underneath the chorion. These results have important implications for pharmacologic/toxicologic techniques like the fish embryo test, which therefore require extended incubation times in order to reach sufficient concentrations in the embryos. PMID:23815821

Regression of altitude-produced cardiac hypertrophy.

NASA Technical Reports Server (NTRS)

Sizemore, D. A.; Mcintyre, T. W.; Van Liere, E. J.; Wilson , M. F.

1973-01-01

The rate of regression of cardiac hypertrophy with time has been determined in adult male albino rats. The hypertrophy was induced by intermittent exposure to simulated high altitude. The percentage hypertrophy was much greater (46%) in the right ventricle than in the left (16%). The regression could be adequately fitted to a single exponential function with a half-time of 6.73 plus or minus 0.71 days (90% CI). There was no significant difference in the rates of regression for the two ventricles.

Quantification of polarized trafficking of transferrin and comparison with bulk membrane transport in hepatic cells

PubMed Central

Wüstner, Daniel

2006-01-01

Transport of the recycling marker transferrin was analysed in polarized hepatic HepG2 cells using quantitative fluorescence microscopy and mathematical modelling. A detailed map and kinetic model for transport of transferrin in hepatic cells was developed. Fluorescent transferrin was found to be transported sequentially through basolateral SE (sorting endosomes) to a SAC/ARC (subapical compartment/apical recycling compartment). DiI (di-indocarbocyanine) lipid probes of different acyl chain length (DiIC12 and DiIC16) co-localized with transferrin in basolateral SE and in the SAC/ARC. By kinetic comparison of hepatic transport of transferrin and labelled HDL (high-density lipoprotein), it is shown that transport of transferrin from SE to the SAC/ARC follows a default pathway together with HDL. Kinetic modelling of fluorescence data provides an identical half-time for SE-to-SAC/ARC transport of transferrin and fluorescent HDL (t½=4.2 min). Fluorescent transferrin was found to recycle with a half-time of t½=12.9 min from the SAC/ARC to the basolateral cell surface of HepG2 cells. In contrast with HDL, targeting of labelled transferrin from the SAC/ARC to the apical biliary canaliculus was negligible. The results indicate that transport from basolateral hepatic SE to the SAC/ARC represents a bulk flow process and that polarized sorting occurs mainly at the level of the SAC/ARC. PMID:16879100

L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug.

PubMed

Goldstein, David S

2006-01-01

L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.

Effect of parenteral administration of erythromycin, tilmicosin, and tylosin on abomasal emptying rate in suckling calves.

PubMed

Nouri, Mohammad; Constable, Peter D

2007-12-01

To determine the effect of parenteral administration of erythromycin, tilmicosin, and tylosin on abomasal emptying rate in suckling calves. 8 male Holstein-Friesian calves < 35 days old. Calves received each of 4 treatments in random order (2 mL of saline [0.9% NaCl] solution, IM [control treatment]; erythromycin, 8.8 mg/kg, IM; tilmicosin, 10 mg/kg, SC; and tylosin, 17.6 mg/kg, IM). Calves were fed 2 L of milk replacer containing acetaminophen (50 mg/kg) 30 minutes later. Jugular venous blood samples and transabdominal ultrasonographic abomasal dimensions were obtained periodically after suckling. Abomasal emptying rate was assessed on the basis of the time to maximal plasma acetaminophen concentration and ultrasonographic determination of the halftime of abomasal emptying. One-tailed Dunnett post tests were conducted whenever the F value for group was significant. Emptying rate was faster for erythromycin, tilimicosin, and tylosin than for the control treatment, as determined on the basis of time to maximal plasma acetaminophen concentration. Ultrasonography indicated that the half-time of abomasal emptying was significantly shorter for erythromycin than for the control treatment. Tylosin and tilmicosin accelerated the abomasal emptying rate, but not significantly, relative to the emptying rate for the control treatment. Administration of erythromycin, tilmicosin, and tylosin at the label dosage increased abomasal emptying rate in calves. The clinical importance of an increase in abomasal emptying rate in cattle remains to be determined.

The Effect of Glycyrrhetinic Acid on Pharmacokinetics of Cortisone and Its Metabolite Cortisol in Rats

PubMed Central

Lin, Dan; Sun, Wei; Wang, Zhe; Chen, Lian-Guo; Chen, Xiao-Le; Wang, Shuang-Hu; Li, Wan-Shu; Ge, Ren-Shan; Hu, Guo-Xin

2012-01-01

The purpose of this paper is to study pharmacokinetics of cortisone (E) and its metabolite cortisol (F) in rats after administration of glycyrrhetinic acid (GA) and cortisone. Healthy male SD rats were randomized to be given 20 mg/kg E or E combined with 10 mg/kg GA. Blood samples were collected at 5, 10, 20, 40, 60, 90, 120, 150, 180, and 240 min after administration. The serum concentrations of E and F were determined by HLPC and pharmacokinetic parameters were calculated using DASver2.0 software. The parameters of AUC(0−t), AUC(0−∞), and Cmax for E in the group of E + GA were significantly higher than those in the group of E (P < 0.01); the half-time (t1/2β) was extended compared to E (P < 0.05) and CL/F was dropped obviously (P < 0.01). The rise in AUC(0−t), AUC(0−∞), and Cmax for cortisol in the group of E + GA was significantly compared to the group of E (P < 0.01). CL/F was lower than E (P < 0.01) and the half-time (t1/2β) was slightly extended. In this study, we find that GA restrains the metabolism of E and F and thus increases AUC, t1/2β, and Cmax of E and F, which may be related to its inhibition effect on 11β-hydroxysteroid dehydrogenase (11β-HSD). PMID:23258958

A modified spectroscopic method for the determination of the transbilayer distribution of phosphatidylethanolamine in soya-bean asolectin small unilamellar vesicles.

PubMed Central

Sarti, P; Molinari, A; Arancia, G; Meloni, A; Citro, G

1995-01-01

A spectroscopic kinetic approach for determining the relative concentrations of phosphatidylethanolamine (PE) exposed on the external and internal layers of small unilamellar vesicles (SUVs) used as a model system and prepared by sonication of purified soya-bean asolectin is proposed, based on the use of 2,4,6-trinitrobenzenesulphonic acid (TNBS) and N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). The known reactions between PE and TNBS and/or SDPD were used, separately or in combination, to derivatize PE in preformed vesicles. We have observed that mixing SUVs with excess TNBS results in a biphasic time course. Kinetic analysis of the data supports the conclusion that external PE is rapidly derivatized (fast phase) with a half-time of 2 min. In the next (slow) phase (half-time 70 min), TNBS permeates the vesicle membrane and also reacts with PE molecules facing the internal liposomal compartment. Under the experimental conditions chosen, SPDP reacted with only the external PE molecules. The reaction of SUVs first derivatized with SPDP and then with TNBS further demonstrates that the two phases, observed with TNBS, are due to modification of external and internal PE. Approx. 30% of PE was found to be facing the external bulk phase, thus confirming the asymmetric distribution of the molecules in SUVs. The maximum number of thiol arms covalently linked by means of SPDP modification of PE on the surface of a single liposome was estimated at about 10(2). Images Figure 1 PMID:8526881

Evidence that downregulation of hexose transport limits intracellular glucose in 3T3-L1 fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitesell, R.R.; Regen, D.M.; Pelletier, D.

1990-10-01

Measurements of initial glucose entry rate and intracellular glucose concentration in cultured cells are difficult because of rapid transport relative to intracellular volume and a substantial extracellular space from which glucose cannot be completely removed by quick exchanges of medium. In 3T3-L1 cells, we obtained good estimates of initial entry of ({sup 14}C)methylglucose and D-({sup 14}C)glucose with (1) L-({sup 3}H)glucose as an extracellular marker together with the ({sup 14}C)glucose or ({sup 14}C)methylglucose in the substrate mixture, (2) sampling times as short as 2 s, (3) ice-cold phloretin-containing medium to stop uptake and rinse away the extracellular label, and (4) nonlinearmore » regression of time courses. Methylglucose equilibrated in two phases--the first with a half-time of 1.7 s and the second with a half-time of 23 s; it eventually equilibrated in an intracellular space of 8 microliters/mg protein. Entry of glucose remained almost linear for 10 s, making its transport kinetics easier to study (Km = 5.7 mM, Vmax = 590 nmol.s-1.ml-1 cell water). Steady-state intracellular glucose concentration was 75-90% of extracellular glucose concentration. Cells grown in a high-glucose medium (24 mM) exhibited a 67% reduction of glucose-transport activity and a 50% reduction of steady-state ratio of intracellular glucose to extracellular glucose.« less

Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B.

1988-04-01

Rotaviruses are icosahedral viruses with a segmented, double-stranded RNA genome. They are the major cause of severe infantile infectious diarrhea. Rotavirus growth in tissue culture is markedly enhanced by pretreatment of virus with trypsin. Trypsin activation is associated with cleavage of the viral hemagglutinin (viral protein 3 (VP3); 88 kilodaltons) into two fragments (60 and 28 kilodaltons). The mechanism by which proteolytic cleavage leads to enhanced growth is unknown. To determine whether trypsin treatment affected rotavirus internalization, the authors studied the kinetics of entry of infectious rhesus rotavirus (RRV) into MA104 cells. Trypsin-activated RRV was internalized with a half-time ofmore » 3 to 5 min, while nonactivated virus disappeared from the cell surface with a half-time of 30 to 50 min. In contrast to trypsin-activated RRV, loss of nonactivated RRV from the cell surface did not result in the appearance of infection, as measured by plaque formation. Purified trypsin-activated RRV added to cell monolayers at pH 7.4 mediated {sup 51}Cr, ({sup 14}C)choline, and ({sup 3}H)inositol released from prelabeled MA104 cells. This release could be specifically blocked by neutralizing antibodies to VP3. These results suggest that MA104 cell infection follows the rapid entry of trypsin-activated RRV by direct cell membrane penetration. Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3. Neutralizing antibodies can inhibit this direct membrane penetration.« less

An ATPase-deficient variant of the SNF2 family member HELLS shows altered dynamics at pericentromeric heterochromatin.

PubMed

Lungu, Cristiana; Muegge, Kathrin; Jeltsch, Albert; Jurkowska, Renata Z

2015-05-22

The HELLS (helicase, lymphoid specific, also known as lymphoid-specific helicase) protein is related to the SNF2 (sucrose non-fermentable 2) family of chromatin remodeling ATPases. It is required for efficient DNA methylation in mammals, particularly at heterochromatin-located repetitive sequences. In this study, we investigated the interaction of HELLS with chromatin and used an ATPase-deficient HELLS variant to address the role of ATP hydrolysis in this process. Chromatin fractionation experiments demonstrated that, in the absence of the ATPase activity, HELLS is retained at the nuclear matrix compartment, defined in part by lamin B1. Microscopy studies revealed a stronger association of the ATPase-deficient mutant with heterochromatin. These results were further supported by fluorescence recovery after photobleaching measurements, which showed that, at heterochromatic sites, wild-type HELLS is very dynamic, with a recovery half-time of 0.8s and a mobile protein fraction of 61%. In contrast, the ATPase-deficient mutant displayed 4.5-s recovery half-time and a reduction in the mobile fraction to 30%. We also present evidence suggesting that, in addition to the ATPase activity, a functional H3K9me3 signaling pathway contributes to an efficient release of HELLS from pericentromeric chromatin. Overall, our results show that a functional ATPase activity is not required for the recruitment of HELLS to heterochromatin, but it is important for the release of the enzyme from these sites. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling the effects of exercise during 100% oxygen prebreathe on the risk of hypobaric decompression sickness

NASA Technical Reports Server (NTRS)

Loftin, K. C.; Conkin, J.; Powell, M. R.

1997-01-01

BACKGROUND: Several previous studies indicated that exercise during prebreathe with 100% O2 decreased the incidence of hypobaric decompression sickness (DCS). We report a meta-analysis of these investigations combined with a new study in our laboratory to develop a statistical model as a predictive tool for DCS. HYPOTHESIS: Exercise during prebreathe increases N2 elimination in a theoretical 360-min half-time compartment decreasing the incidence of DCS. METHODS: A dose-response probability tissue ratio (TR) model with 95% confidence limits was created for two groups, prebreathe with exercise (n = 113) and resting prebreathe (n = 113), using nonlinear regression analysis with maximum likelihood optimization. RESULTS: The model predicted that prebreathe exercise would reduce the residual N2 in a 360-min half-time compartment to a level analogous to that in a 180-min compartment. This finding supported the hypothesis. The incidence of DCS for the exercise prebreathe group was significantly decreased (Chi-Square = 17.1, p < 0.0001) from the resting prebreathe group. CONCLUSIONS: The results suggested that exercise during prebreathe increases tissue perfusion and N2 elimination approximately 2-fold and markedly lowers the risk of DCS. Based on the model, the prebreathe duration may be reduced from 240 min to a predicted 91 min for the protocol in our study, but this remains to be verified. The model provides a useful planning tool to develop and test appropriate prebreathe exercise protocols and to predict DCS risks for astronauts.

The use of 123I-labeled heptadecanoic acid (HDA) as metabolic tracer: preliminary report.

PubMed

Dudczak, R; Kletter, K; Frischauf, H; Losert, U; Angelberger, P; Schmoliner, R

1984-01-01

The feasibility of using 123I-heptadecanoic acid (HDA) as a metabolic tracer was studied. Different administration routes of HDA were compared. An intracoronary bolus injection was given to calves (n = 3), and an intravenous injection was given to patients (n = 4). In addition, we examined the influence of 4-h halothane anesthesia in calves and in patients the impact of an insulin (1.5 IU/kg) + glucose (1.5 g/kg) infusion on the myocardial kinetics of HDA. Data were accumulated with a scintillation probe in calves (t = 50 min) and a gamma camera in patients (t = 70 min). In calves after an intracoronary bolus injection of HDA the myocardial time-activity curve could be described by two exponentials. The mean elimination half-time of the initial phase (ta 1/2) was 7.3 min and that of the second phase (tb 1/2) was 35 min. The ratio of the size of the initial and second component at to was 0.93. Halothane anesthesia prolonged the elimination half-times and reduced the component ratio. The biphasic behavior of the myocardial time-activity curve was maintained in patients after intravenous administration of HDA under basal conditions (initial ta 1/2 = 8.4 min). However, during infusion of insulin + glucose the decline in the myocardial activity was prolonged and monoexponential. This data shows that insulin glucose, interfering with fatty acid metabolism, influences the myocardial washout of HDA, and thus support its use as a metabolic tracer.

Effect of glyburide on in vivo recycling of the hepatic insulin receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, H.J.; Donohoe, M.T.; Morris, W.L.

1985-09-20

Sulfonylureas affect insulin action at both receptor and post-receptor sites, but their exact mechanism is poorly understood. In these studies, a novel technique was used to examine the influence of glyburide on in vivo cycling of the hepatic insulin receptor. Rats were gavage-fed with 5 mg/kg per day of glyburide solubilized in 60 percent polyethylene glycol and 40 percent phosphate buffer. Control rats were fed polyethylene glycol and buffer alone. After seven days, each rat was anesthetized, the abdomen was surgically exposed, and the animal was given a saturating bolus of 30 micrograms of unlabeled insulin via the portal vein.more » At seven specified times from 10 seconds to 45 minutes later, a second portal vein injection of a mixture of 1.5 microCi (0.015 micrograms) SVI-labeled insulin and 15 microCi THOH (a highly diffusible internal reference marker) was administered; 18 seconds later (time for one circulation), the right lobe of the liver was removed, and SVI and TH values were counted. The liver uptake index and the turnover half-time were then calculated. Glyburide caused a doubling of the turnover half-time for the receptor. This suggests that sulfonylureas potentiate the action of insulin either by increasing the dwell time of insulin on its receptor or by affecting an intracellular event that delays the recycling of the insulin receptor back to the cell surface plasma membrane.« less

Refinements in the short-circuit technique and its application to active potassium transport across the cecropia midgut.

PubMed

Wood, J L; Moreton, R B

1978-12-01

1. The conventional, two-electrode method for measuring potential difference across an epithelium is subject to error due to potential gradients caused by current flow in the bathing medium. Mathematical analysis shows that the error in measuring short-circuit current is proportional to the resistivity of the bathing medium and to the separation of the two recording electrodes. It is particularly serious for the insect larval midgut, where the resistivity of the medium is high, and that of the tissue is low. 2. A system has been devised, which uses a third recording electrode to monitor directly the potential gradient in the bathing medium. By suitable electrical connexions, the gradient can be automatically compensated, leaving a residual error which depends on the thickness of the tissue, but not on the electrode separation. Because the thicknesses of most epithelia are smaller than the smallest practical electrode spacing, this error is smaller than that inherent in a two-electrode system. 3. Since voltage-gradients are automatically compensated, it is possible to obtain continuous readings of potential and current. A 'voltage-clamp' circuit is described, which allows the time-course of the short-circuit current to be studied. 4.The three-electrode system has been used to study the larval midgut of Hyalophora cecropia. The average results from five experiments were: initial potential difference (open-circuit): 98+/-11 mV (S.E.M.); short-circuit current at time 60 min: 498+/-160 microA cm=2; 'steady-state' resistance at 60 min: 150+/-26 omega cm2. The current is equivalent to a net potassium transport of 18.6 mu-equiv cm-2 h-1. 5. The electrical parameters of the midgut change rapidly with time. The potential difference decays with a half-time of about 158 min, the resistance increases with a half-time of about 16 min, and the short-circuit current decays as the sum of two exponential terms, with half-times of about 16 and 158 min respectively. In addition, potential and short-circuit current show transient responses to step changes. 6. The properties of the midgut are compared with those of other transporting epithelia, and their dependence on the degree of folding of the preparation is discussed. Their time-dependence is discussed in the context of changes in potassium content of the tissue, and the implications for measurements depending on the assumption of a steady state are outlined.

STS-27 crew poses for inflight portrait on forward flight deck with football

NASA Image and Video Library

1988-12-06

STS027-11-012 (2-6 Dec. 1988) --- The crew members for the STS-27 space flight pose on the flight deck of the Earth-orbiting space shuttle Atlantis with a football free-floating in the foreground. Left to right are astronauts Robert L. Gibson, commander; Richard M. (Mike) Mullane, Jerry L. Ross and William M. Shepherd, mission specialists; and Guy S. Gardner, pilot. The football was later presented to the National Football League (NFL) at halftime of the Super Bowl in Miami. Photo credit: NASA

Timely access to specialist medical oncology services closer to home for rural patients: experience from the Townsville Teleoncology Model.

PubMed

Sabesan, Sabe; Roberts, Lynden J; Aiken, Peter; Joshi, Abhishek; Larkins, Sarah

2014-08-01

Prior to 2009, the teleoncology model of the Townsville Cancer Centre (TCC) did not achieve its aims of equal waiting times for rural and urban patients and the provision of reliable, local acute cancer care. From 2007-2009, 60 new patients from Mt Isa travelled to TCC for their first consultation and their first dose of chemotherapy. Six of these patients required inter-hospital transfers and eight required urgent flights to attend outpatient clinics. Only 50% these rural patients (n = 30) were reviewed within one week of their referral, compared with 90% of Townsville patients. A descriptive study. TCC provides teleoncology services to 21 rural towns; the largest is Mt Isa, Qld. Specialist review of 90% of urgent cases within 24 hours, and 90% of non-urgent cases within one week of referral via videoconferencing. A 50% reduction in inpatient inter-hospital transfers from Mt Isa to Townsville. Employment of a half-time medical officer and a half-time cancer care coordinator, and implementation of new policies. Between 2009 and 2011, TCC provided cancer care to 70 new patients from Mt Isa. Of these new patients, 93% (65/70) were seen within one week of referral. All 17 patients requiring urgent reviews were seen within 24 hours of referral and managed locally thus eliminating the need for inpatient inter-hospital transfers. Provision of timely acute cancer care closer to home requires an increase in the rural case complexity and human resources. © 2014 National Rural Health Alliance Inc.

Match-play demands of elite youth Gaelic football using global positioning system tracking.

PubMed

Reilly, Brian; Akubat, Ibrahim; Lyons, Mark; Collins, D Kieran

2015-04-01

Global positioning systems (GPS) technology has made athlete-tracking a convenient and accepted technique to specify movement patterns and physical demands in sport. The purpose of this study was to examine positional demands of elite youth Gaelic football match-play using portable GPS technology to examine movement patterns and heart rates across match periods. Fifty-six elite youth male Gaelic footballers (age, 15 ± 0.66 years) fitted with portable 4-Hz GPS units were observed during 6 competitive matches (60 minutes). Data provided from the GPS unit included total distance, high-intensity (≥17·km·h(-1)) distance, sprint (≥22 km·h(-1)) distance, and total number of sprints. Heart rate was monitored continuously throughout the games. Players covered a mean distance of 5732 ± 1047 m, and the mean intensity of match-play was 85% of the peak heart rate. There was a significant (p = 0.028) drop in the total distance covered in the second half (2783 ± 599 m) compared with the first half (2948 ± 580 m). In particular, there is a noticeable drop in the distance covered in the third quarter of the game (after half-time), which has implications for re-warming up at the end of the half-time interval. There was a highly significant (p < .001) difference in the distance traveled across the 5 positional groups with midfielders covering the greatest total distance (6740 ± 384 m). The significant differences found with respect to positional groups support the implementation of individual, position-specific strength and conditioning programs.

Indices of fiber biopersistence and carcinogen classification for synthetic vitreous fibers (SVFs).

PubMed

Maxim, L Daniel; Boymel, Paul; Chase, Gerald R; Bernstein, David M

2002-06-01

It is generally accepted that the biopersistence of a synthetic vitreous fiber (SVF) is an important determinant of its biological activity. Experimental protocols have been developed to measure the biopersistence of an SVF from short-term inhalation experiments with rats. Clearance kinetics of long (>20 microm) fibers (those believed to have greatest biological activity) have been approximated by one- or two-pool models. Several measures or indices of biopersistence have been proposed in the literature of which three, the weighted half-time (WT(1/2)), the time required to clear 90% of long fibers (T(0.9)), and the so-called slow-phase half-time (T(2)), have been investigated in some detail. This paper considers both one- and two-pool models for long fiber clearance, characterizes the properties of these candidate indices of fiber biopersistence, identifies measures with potentially superior statistical properties, suggests possible cutoff values based on the relation between biopersistence and the outcome of chronic bioassays, and offers comments on the selection of efficient experimental designs. This analysis concludes that WT(1/2) and T(0.9) are highly correlated, are efficient predictors of the outcome of chronic bioassays, and have reasonable statistical properties. T(2), although perhaps attractive in principle, suffers from some statistical shortcomings when estimated using present experimental protocols. The WT(1/2) is shown to be directly proportional to the cumulative exposure (fiber days) after the cessation of exposure and also the mean residence time of these fibers in the lung. Copyright 2002 Elsevier Science (USA)

New Concepts in the Evaluation of Biodegradation/Persistence of Chemical Substances Using a Microbial Inoculum

PubMed Central

Thouand, Gérald; Durand, Marie-José; Maul, Armand; Gancet, Christian; Blok, Han

2011-01-01

The European REACH Regulation (Registration, Evaluation, Authorization of CHemical substances) implies, among other things, the evaluation of the biodegradability of chemical substances produced by industry. A large set of test methods is available including detailed information on the appropriate conditions for testing. However, the inoculum used for these tests constitutes a “black box.” If biodegradation is achievable from the growth of a small group of specific microbial species with the substance as the only carbon source, the result of the test depends largely on the cell density of this group at “time zero.” If these species are relatively rare in an inoculum that is normally used, the likelihood of inoculating a test with sufficient specific cells becomes a matter of probability. Normally this probability increases with total cell density and with the diversity of species in the inoculum. Furthermore the history of the inoculum, e.g., a possible pre-exposure to the test substance or similar substances will have a significant influence on the probability. A high probability can be expected for substances that are widely used and regularly released into the environment, whereas a low probability can be expected for new xenobiotic substances that have not yet been released into the environment. Be that as it may, once the inoculum sample contains sufficient specific degraders, the performance of the biodegradation will follow a typical S shaped growth curve which depends on the specific growth rate under laboratory conditions, the so called F/M ratio (ratio between food and biomass) and the more or less toxic recalcitrant, but possible, metabolites. Normally regulators require the evaluation of the growth curve using a simple approach such as half-time. Unfortunately probability and biodegradation half-time are very often confused. As the half-time values reflect laboratory conditions which are quite different from environmental conditions (after a substance is released), these values should not be used to quantify and predict environmental behavior. The probability value could be of much greater benefit for predictions under realistic conditions. The main issue in the evaluation of probability is that the result is not based on a single inoculum from an environmental sample, but on a variety of samples. These samples can be representative of regional or local areas, climate regions, water types, and history, e.g., pristine or polluted. The above concept has provided us with a new approach, namely “Probabio.” With this approach, persistence is not only regarded as a simple intrinsic property of a substance, but also as the capability of various environmental samples to degrade a substance under realistic exposure conditions and F/M ratio. PMID:21863143

Decompression Sickness After Air Break in Prebreathe Described with a Survival Model

NASA Technical Reports Server (NTRS)

Conkin, J.; Pilmanis, A. A.

2010-01-01

Data from Brooks City-Base show the decompression sickness (DCS) and venous gas emboli (VGE) consequences of air breaks in a resting 100% O2 prebreathe (PB) prior to a hypobaric exposure. METHODS: DCS and VGE survival times from 95 controls for a 60 min PB prior to 2-hr or 4-hr exposures to 4.37 psia are statistically compared to 3 break in PB conditions: a 10 min (n=40), 20 min (n=40), or 60 min break (n=32) 30 min into the PB followed by 30 min of PB. Ascent rate was 1,524 meters / min and all exposures included light exercise and 4 min of VGE monitoring of heart chambers at 16 min intervals. DCS survival time for combined control and air breaks were described with an accelerated log logistic model where exponential N2 washin during air break was described with a 10 min half-time and washout during PB with a 60 min half-time. RESULTS: There was no difference in VGE or DCS survival times among 3 different air breaks, or when air breaks were compared to control VGE times. However, 10, 20, and 60 min air breaks had significantly earlier survival times compared to control DCS times, certainly early in the exposures. CONCLUSION: Air breaks of 10, 20, and 60 min after 30 min of a 60 min PB reduced DCS survival time. The survival model combined discrete comparisons into a global description mechanistically linked to asymmetrical N2 washin and washout kinetics based on inspired pN2. Our unvalidated regression is used to compute additional PB time needed to compensate for an air break in PB within the range of tested conditions.

Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure.

PubMed

Goldstein, David S; Holmes, Courtney; Kaufmann, Horacio; Freeman, Roy

2004-12-01

Oral L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic catechol amino acid, increases standing blood pressure and improves standing ability in patients with neurogenic orthostatic hypotension, by conversion of L-DOPS to norepinephrine (NE) outside the brain. This study assessed the pharmacokinetics of L-DOPS, NE, and dihydroxyphenylglycol (DHPG), the main neuronal metabolite of NE, in patients with primary chronic autonomic failure from pure autonomic failure (PAF) or multiple system atrophy (MSA). In 5 MSA and 4 PAF patients, antecubital venous blood was drawn during supine rest and plasma levels of catechols measured at various times for 48 hours after a single oral dose of 400 mg of L-DOPS. Plasma L-DOPS peaked at 1.9 microg/ml (9 micromol/L) about 3 hours after drug administration, followed by a monoexponential decline with a half-time of 2-3 hours in both patient groups. Plasma NE and DHPG also peaked at about 3 hours, but at much lower concentrations (4 and 42 nmol/L). Compared to the MSA group, the PAF group had a smaller calculated volume of distribution of L-DOPS and up to 10-fold lower plasma NE levels at all time points. Plasma NE was above baseline in MSA even at 48 hours after L-DOPS. The relatively long half-time for disappearance of L-DOPS compared to that of NE explains their very different attained plasma concentrations. The similar NE and DHPG responses in PAF and MSA suggests production of NE from LDOPS mainly in non-neuronal cells. Persistent elevation of plasma NE in MSA suggests residual release of NE from sympathetic nerves.

Gastric emptying and orocaecal transit time of meals containing lactulose or inulin in men.

PubMed

Clegg, Miriam; Shafat, Amir

2010-08-01

The H(2) breath test is ideal for orocaecal transit time (OCTT) measurement, as it is non-invasive and inexpensive. Indigestible substrates added to a test meal are metabolised by the colonic bacteria, resulting in the production of H(2) which is detected in end-exhalation breath. However, the substrates themselves can alter the transit times in the gastrointestinal tract. The aim of the present study is to compare OCTT and gastric emptying (GE) when lactulose in liquid (L-L), solid lactulose (L-S) and solid inulin (IN-S) are added to a test meal, and subsequently, to examine if inulin alters GE. Firstly, ten male volunteers were tested on three occasions. Volunteers ate a pancake breakfast containing 100 mg of (13)C-octanoic acid and either 12 g of L-L, 12 g of L-S or 12 g of IN-S in a randomised order. Secondly, seven male volunteers were tested twice with meals containing either 12 g of IN-S or no substrate (NO-S). L-L induced the shortest OCTT (85.3 (sd 42.8) min) compared with L-S (162.4 (sd 62.6) min) and inulin (292.4 (sd 66.7) min; P = 0.007). GE half-time and lag phase (L-L: 61 (sd 9); L-S: 57 (sd 10); IN-S: 52 (sd 10) min; P = 0.005) were also affected, with L-L being the slowest. Thirdly, inulin reduced GE lag and latency phases (P < 0.05) compared with NO-S. Lactulose accelerates OCTT but delays GE compared with inulin. Inulin accelerates the onset of stomach emptying, but it has no effect on GE half-time. For these reasons, inulin is the preferred substrate for the H(2) breath test.

Analysis of factors that influence rates of carbon monoxide uptake, distribution, and washout from blood and extravascular tissues using a multicompartment model.

PubMed

Bruce, Margaret C; Bruce, Eugene N

2006-04-01

To better understand factors that influence carbon monoxide (CO) washout rates, we utilized a multicompartment mathematical model to predict rates of CO uptake, distribution in vascular and extravascular (muscle vs. other soft tissue) compartments, and washout over a range of exposure and washout conditions with varied subject-specific parameters. We fitted this model to experimental data from 15 human subjects, for whom subject-specific parameters were known, multiple washout carboxyhemoglobin (COHb) levels were available, and CO exposure conditions were identical, to investigate the contributions of exposure conditions and individual variability to CO washout from blood. We found that CO washout from venous blood was biphasic and that postexposure times at which COHb samples were obtained significantly influenced the calculated CO half times (P < 0.0001). The first, more rapid, phase of CO washout from the blood reflected the loss of CO to the expired air and to a slow uptake by the muscle compartment, whereas the second, slower washout phase was attributable to CO flow from the muscle compartment back to the blood and removal from blood via the expired air. When the model was used to predict the effects of varying exposure conditions for these subjects, the CO exposure duration, concentration, peak COHb levels, and subject-specific parameters each influenced washout half times. Blood volume divided by ventilation correlated better with half-time predictions than did cardiac output, muscle mass, or ventilation, but it explained only approximately 50% of half-time variability. Thus exposure conditions, COHb sampling times, and individual parameters should be considered when estimating CO washout rates for poisoning victims.

Scintigraphic studies on the corneal residence of a New Ophthalmic Delivery System (NODS): rate of clearance of a soluble marker in relation to duration of pharmacological action of pilocarpine.

PubMed Central

Greaves, J L; Wilson, C G; Birmingham, A T; Richardson, M C; Bentley, P H

1992-01-01

1. A gamma scintigraphic study has been carried out on the precorneal residence and pharmacodynamic action of a radiolabelled New Ophthalmic Delivery System (NODS) containing pilocarpine nitrate in 12 healthy volunteers. 2. The NODS was radiolabelled with the soluble marker technetium-99m labelled diethylenetriaminepentaacetic acid, to mark the release characteristics of soluble drugs contained within the matrix. 3. The relationship between the precorneal residence time of the marker and the duration of drug effect on intraocular pressure and pupil diameter was monitored. Results obtained following administration of the NODS were compared with those obtained after administration of a 25 microliters drop of a 2% w/v pilocarpine nitrate solution. Each formulation was administered to one eye only, the other eye acting as a control. 4. Dissolution of the radiolabel from the NODS in vivo showed considerable intersubject variation with half-times of dissolution ranging from 46 s to 833 s (mean +/- s.d. -280 +/- 217 s), the mean (+/- s.d.) half-time of clearance of the radiolabel from the NODS and corneal region of interest was 406 +/- 214 s whereas the radiolabelled solution had a mean (+/- s.d.) ocular surface residence time of 2.9 +/- 1.5 s. 5. Pupil diameter and intraocular pressure were measured for 5 h post-administration of the NODS and the solution. After both treatments pupil diameter was significantly constricted in the test eye when compared with the control eye (P less than 0.001; Student's paired t-test). Pupil diameter was constricted by 52% after administration of the NODS and by 35% after administration of the solution.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 PMID:1389932

Scintigraphic studies on the corneal residence of a New Ophthalmic Delivery System (NODS): rate of clearance of a soluble marker in relation to duration of pharmacological action of pilocarpine.

PubMed

Greaves, J L; Wilson, C G; Birmingham, A T; Richardson, M C; Bentley, P H

1992-06-01

1. A gamma scintigraphic study has been carried out on the precorneal residence and pharmacodynamic action of a radiolabelled New Ophthalmic Delivery System (NODS) containing pilocarpine nitrate in 12 healthy volunteers. 2. The NODS was radiolabelled with the soluble marker technetium-99m labelled diethylenetriaminepentaacetic acid, to mark the release characteristics of soluble drugs contained within the matrix. 3. The relationship between the precorneal residence time of the marker and the duration of drug effect on intraocular pressure and pupil diameter was monitored. Results obtained following administration of the NODS were compared with those obtained after administration of a 25 microliters drop of a 2% w/v pilocarpine nitrate solution. Each formulation was administered to one eye only, the other eye acting as a control. 4. Dissolution of the radiolabel from the NODS in vivo showed considerable intersubject variation with half-times of dissolution ranging from 46 s to 833 s (mean +/- s.d. -280 +/- 217 s), the mean (+/- s.d.) half-time of clearance of the radiolabel from the NODS and corneal region of interest was 406 +/- 214 s whereas the radiolabelled solution had a mean (+/- s.d.) ocular surface residence time of 2.9 +/- 1.5 s. 5. Pupil diameter and intraocular pressure were measured for 5 h post-administration of the NODS and the solution. After both treatments pupil diameter was significantly constricted in the test eye when compared with the control eye (P less than 0.001; Student's paired t-test). Pupil diameter was constricted by 52% after administration of the NODS and by 35% after administration of the solution.(ABSTRACT TRUNCATED AT 250 WORDS)

[Improvement of thermostability of beta-1,3-1,4-glucanase from Bacillus amyloliquefaciens BS5582 through in vitro evolution].

PubMed

Qin, Jiufu; Gao, Weiwei; Li, Qi; Li, Yongxian; Zheng, Feiyun; Liu, Chunfeng; Gu, Guoxian

2010-09-01

In vitro evolution methods are often used to modify protein with improved characteristics. We developed a directed evolution protocol to enhance the thermostability of the beta-1,3-1,4-glucanase. The thermostability of the enzyme was significantly improved after two rounds of directed evolution. Three variants with higher thermostability were obtained. The mutant enzymes were further analyzed by their melting temperature, halftime and kinetic parameters. Comparing to intact enzyme, the T50 of mutant enzymes 2-JF-01, 2-JF-02 and 2-JF-03 were increased by 2.2 degrees C, 5.5 degrees C and 3.5 degrees C, respectively, the halftime (t1/2, 60 degrees C) of mutant enzymes 2-JF-01, 2-JF-02 and 2-JF-03 were shortened by 4,13 and 17 min, respectively, the V(max) of mutant enzymes were decreased by 8.3%, 2.6% and 10.6%, respectively, while K(m) of mutant enzymes were nearly unchanged. Sequence analysis revealed seven single amino acid mutant happened among three mutant enzymes, such as 2-JF-01 (N36S, G213R), 2-JF-02 (C86R, S115I, N150G) and 2-JF-03 (E156V, K105R). Homology-modeling showed that five of seven substituted amino acids were located on the surface of or in hole of protein. 42.8% of substituted amino acids were arginine, which indicated that arginine may play a role in the improvement of the thermostability of the beta-1,3-1,4-glucanase.This study provide some intresting results of the structural basis of the thermostability of beta-1,3-1,4-glucanase,and provide some new point of view in modifying enzyme for future industrial use.

Effect of Solar Radiation on the Optical Properties and Molecular Composition of Laboratory Proxies of Atmospheric Brown Carbon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Hyun Ji; Aiona, Paige K.; Laskin, Alexander

2014-09-02

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 solar photolysis on the molecular composition, mass absorption coefficient, and fluorescence of secondary organic aerosol prepared by high-NO x photooxidation of naphthalene (NAP SOA). The aqueous solutions of NAP SOA was observed to photobleach with an effective half-time of ~15 hours (with sun in its zenith) for the loss of the near-UV (300 -400 nm) absorbance. The molecular compositionmore » of NAP SOA was significantly modified by photolysis, with the average SOA formula changing from C 14.1H 14.5O 5.1N 0.08 to C 11.8H 14.9O 4.5N 0.02 after 4 hours of irradiation. The average O/C ratio did not change significantly, however, 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 photolysis of BrC material produced by aqueous reaction of limonene+O 3 SOA (LIM/O 3 SOA) with ammonium sulfate was much faster, but it did not result in a significant change in the molecular level composition. The characteristic absorbance of the aged LIM/O 3 SOA in the 450-600 nm range decayed with an effective half-time of <0.5 hour. This result emphasizes the highly variable and dynamic nature of different types of atmospheric BrC.« less

Distribution of crystalloid fluid changes with the rate of infusion: a population-based study.

PubMed

Hahn, R G; Drobin, D; Zdolsek, J

2016-05-01

Crystalloid fluid requires 30 min for complete distribution throughout the extracellular fluid space and tends to cause long-standing peripheral edema. A kinetic analysis of the distribution of Ringer's acetate with increasing infusion rates was performed to obtain a better understanding of these characteristics of crystalloids. Data were retrieved from six studies in which 76 volunteers and preoperative patients had received between 300 ml and 2375 ml of Ringer's acetate solution at a rate of 20-80 ml/min (0.33-0.83 ml/min/kg). Serial measurements of the blood hemoglobin concentration were used as inputs in a kinetic analysis based on a two-volume model with micro-constants, using software for nonlinear mixed effects. The micro-constants describing distribution (k12) and elimination (k10) were unchanged when the rate of infusion increased, with half-times of 16 and 26 min, respectively. In contrast, the micro-constant describing how rapidly the already distributed fluid left the peripheral space (k21) decreased by 90% when the fluid was infused more rapidly, corresponding to an increase in the half-time from 3 to 30 min. The central volume of distribution (V(c)) doubled. The return of Ringer's acetate from the peripheral fluid compartment to the plasma was slower with high than with low infusion rates. Edema is a normal consequence of plasma volume expansion with this fluid, even in healthy volunteers. The results are consistent with the view that the viscoelastic properties of the interstitial matrix are responsible for the distribution and redistribution characteristics of crystalloid fluid. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The efficacy and characteristics of warm-up and re-warm-up practices in soccer players: a systematic review.

PubMed

Hammami, Amri; Zois, James; Slimani, Maamer; Russel, Mark; Bouhlel, Ezdine

2018-01-01

This review aimed 1) to evaluate the current research that examines the efficacy of warm-up (WU) and re-warm-up (RWU) on physical performance; and 2) to highlight the WU and RWU characteristics that optimise subsequent performance in soccer players. A computerized search was performed in the PubMed, ScienceDirect and Google Scholar (from 1995 to December 2015) for English-language, peer-reviewed investigations using the terms "soccer" OR "football" AND "warm-up" OR "stretching" OR "post-activation potentiation" OR "pre-activity" OR "re-warm-up" AND "performance" OR "jump" OR "sprint" OR "running". Twenty seven articles were retrieved. Particularly, 22 articles examined the effects of WU on soccer performance and 5 articles focused on the effects of RWU. Clear evidence exists supporting the inclusion of dynamic stretching or postactivation potentiation-based exercises within a WU as acute performance enhancements were reported (pooled estimate changes of +3.46% and +4.21%, respectively). The FIFA 11+ WU also significantly increases strength, jump, speed and explosive performances (changes from 1% to 20%). At half-time, active RWU protocols including postactivation potentiation practices and multidirectional speed drills attenuate temperature and performance reductions induced by habitual practice. The data obtained in the present review showed that the level of play did not moderate the effectiveness of WU and RWU on soccer performance. This review demonstrated that a static stretching WU reduced acute subsequent performance, while WU activities that include dynamic stretching, PAP-based exercises, and the FIFA 11+ can elicit positive effects in soccer players. The efficacy of an active RWU during half-time is also justified.

A Biopersistence Study following Exposure to Chrysotile Asbestos Alone or in Combination with Fine Particles

PubMed Central

Bernstein, D. M.; Donaldson, K.; Decker, U.; Gaering, S.; Kunzendorf, P.; Chevalier, J.; Holm, S. E.

2008-01-01

In designing a study to evaluate the inhalation biopersistence of a chrysotile asbestos that was used as a component of a joint-compound, a feasibility study was initiated to evaluate the short-term biopersistence of the chrysotile alone and of the chrysotile in combination witht the sanded reformulated joint-compound. Two groups of Wistar rats were exposed to either 7RF3 chrysotile (Group 2) or to 7RF3 chrysotile combined with aerosolized sanded joint-compound (Group 3). In addition, a control group was exposed to flltered-air. The chrysotile used in the Ready Mix joint compound is rapidly removed from the lung. The chrysotile alone exposure group had a clearance half-time of fibers L > 20 μm of 2.2 days; in the chrysotile plus sanded exposure group the clearance half-time of fibers L > 20 μm was 2.8 days. However, across all size ranges there was approximately an order of magnitude decrease in the mean number of fibers remaining in the lungs of Group 3 as compared to Group 2 despite similiar aerosol exposures. Histopathological examination showed that the chrysotile exposed lungs had the same appearance as the flltered-air controls. This study uniquely illustrates that additional concurrent exposure to an aerosol of the sanded joint-compound, with large numbers of fine-particles depositing in the lungs, accelerates the recruitment of macrophages, resulting in a tenfold decrease in the number of fibers remaining in the lung. The increased number of macrophages in the chrysotile/sanded joint exposure group was confirmed histologically, with this being the only exposure-related histological finding reported. PMID:18788018

Activation Mobilizes the Cholesterol in the Late Endosomes-Lysosomes of Niemann Pick Type C Cells

PubMed Central

Lange, Yvonne; Ye, Jin; Steck, Theodore L.

2012-01-01

A variety of intercalating amphipaths increase the chemical activity of plasma membrane cholesterol. To test whether intracellular cholesterol can be similarly activated, we examined NPC1 and NPC2 fibroblasts, since they accumulate large amounts of cholesterol in their late endosomes and lysosomes (LE/L). We gauged the mobility of intracellular sterol from its appearance at the surface of the intact cells, as determined by its susceptibility to cholesterol oxidase and its isotope exchange with extracellular 2-(hydroxypropyl)-β-cyclodextrin-cholesterol. The entire cytoplasmic cholesterol pool in these cells was mobile, exchanging with the plasma membrane with an apparent half-time of ∼3–4 hours, ∼4–5 times slower than that for wild type human fibroblasts (half-time ∼0.75 hours). The mobility of the intracellular cholesterol was increased by the membrane-intercalating amphipaths chlorpromazine and 1-octanol. Chlorpromazine also promoted the net transfer of LE/L cholesterol to serum and cyclodextrin. Surprisingly, the mobility of LE/L cholesterol was greatly stimulated by treating intact NPC cells with glutaraldehyde or formaldehyde. Similar effects were seen with wild type fibroblasts in which the LE/L cholesterol pool had been expanded using U18666A. We also showed that the cholesterol in the intracellular membranes of fixed wild-type fibroblasts was mobile; it was rapidly oxidized by cholesterol oxidase and was rapidly replenished by exogenous sterol. We conclude that a) the cholesterol in NPC cells can exit the LE/L (and the extensive membranous inclusions therein) over a few hours; b) this mobility is stimulated by the activation of the cholesterol with intercalating amphipaths; c) intracellular cholesterol is even more mobile in fixed cells; and d) amphipaths that activate cholesterol might be useful in treating NPC disease. PMID:22276143

Long-Term Kinetics of Serum and Xanthoma Cholesterol Radioactivity in Patients with Hypercholesterolemia

PubMed Central

Samuel, Paul; Perl, William; Holtzman, Charles M.; Rochman, Norman D.; Lieberman, Sidney

1972-01-01

In four patients with hypercholesterolemia (type II hyperlipoproteinemia) and xanthomatosis the decay of serum cholesterol specific activity was followed for 53-63 wk after pulse labeling. Specific activity of biopsied xanthoma cholesterol was measured four times in the course of the study. The xanthoma specific activity curve crossed and thereafter remained above the serum specific activity curve. The average ratio of xanthoma to serum specific activity was 4.7 at the end of the study. The final half-time of the xanthoma decay curves was significantly greater (average: 200 days) than the slowest half-time of serum specific activity decay (average: 93 days). The data were analyzed by input-output analysis and yielded the following results. The average value for the total input rate of body cholesterol (IT) (sum of dietary and biosynthesized cholesterol) was 1.29 g/day. The average size of the rapidly miscible pool of cholesterol (Ma) was 55.7 g. and of the total exchangeable body mass of cholesterol (M) 116.5 g. The average value of M - Ma (remaining exchangeable mass of cholesterol) was 60.8 g. The derived values for exchangeable masses of cholesterol, in the present patients with marked hypercholesterolemia, were significantly larger than in a group of patients with normal serum lipids in previous studies. One of the four patients died of a sudden acute myocardial infarction 53 wk after pulse labeling. Specific activity of aortic wall and atheroma cholesterol was 3.12 times that of serum. The ratio was close to 2 for adipose tissue and spleen, and was slightly above 1 or was close to unity in most other organs studied, with the exception of brain which showed a ratio of 0.19. PMID:5009114

Biopersistence of inhaled organic and inorganic fibers in the lungs of rats.

PubMed Central

Warheit, D B; Hartsky, M A; McHugh, T A; Kellar, K A

1994-01-01

Fiber dimension and durability are recognized as important features in influencing the development of pulmonary carcinogenic and fibrogenic effects. Using a short-term inhalation bioassay, we have studied pulmonary deposition and clearance patterns and evaluated and compared the pulmonary toxicity of two previously tested reference materials, an inhaled organic fiber, Kevlar para-aramid fibrils, and an inorganic fiber, wollastonite. Rats were exposed for 5 days to aerosols of Kevlar fibrils (900-1344 f/cc; 9-11 mg/m3) or wollastonite fibers (800 f/cc; 115 mg/m3). The lungs of exposed rats were digested to quantify dose, fiber dimensional changes over time, and clearance kinetics. The results showed that inhaled wollastonite fibers were cleared rapidly with a retention half-time of < 1 week. Mean fiber lengths decreased from 11 microns to 6 microns over a 1-month period, and fiber diameters increased from 0.5 micron to 1.0 micron in the same time. Fiber clearance studies with Kevlar showed a transient increase in the numbers of retained fibrils at 1 week postexposure, with rapid clearance of fibers thereafter, and retention half-time of 30 days. A progressive decrease in the mean lengths from 12.5 microns to 7.5 microns and mean diameters from 0.33 micron to 0.23 micron was recorded 6 months after exposure to inhaled Kevlar fibrils. The percentages of fibers > 15 microns in length decreased from 30% immediately after exposure to 5% after 6 months; the percentages of fibers in the 4 to 7 microns range increased from 25 to 55% in the same period.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 4. A Figure 4. B Figure 6. A Figure 6. B PMID:7882921

Kinetics of the subtransition in dipalmitoylphosphatidylcholine.

PubMed

Tristram-Nagle, S; Wiener, M C; Yang, C P; Nagle, J F

1987-07-14

The kinetics of the interconversions of the subgel and gel phases in dipalmitoylphosphatidylcholine have been studied by using differential dilatometry, differential scanning calorimetry (DSC), and neutral buoyancy centrifugation as a function of incubation temperature and deuteriation of the solvent. As seen by others, DSC scans show two peaks in the subgel transition region for incubation temperatures below 1 degree C. After incubation at 0.1 degree C, the DSC peak that occurs at the lower scanning temperature appears with an incubation half-time of 0.5 day and eventually converts into a peak at higher scanning temperature with an incubation half-time of 18 days. By varying the scanning rate, we show that these two peaks merge into one at slow scanning rates with a common equilibrium transition temperature of 13.8 degrees C, in agreement with equilibrium calorimetry and dilatometry (delta V = 0.017 +/- 0.001 mL/g). For incubation temperatures above 4.6 degrees C, only one peak appears in both scanning dilatometry and calorimetry. While the initial rate of subgel conversion is smaller at the higher incubation temperatures, after 300 h a higher percentage of the sample has converted to subgel than at the lower incubation temperatures. We suggest that higher incubation temperatures (near 5 degrees C) are preferable for forming the stable subgel phase, and we present a colliding domain picture that indicates why this may be so. Our results in D2O and the similarity of the kinetics of volume decrease with the kinetics of wide-angle diffraction lines also support the suggestion that the partial loss of interlamellar water plays a kinetic role in subgel formation.

Roles of affinity and lipophilicity in the slow kinetics of prostanoid receptor antagonists on isolated smooth muscle preparations

PubMed Central

Jones, RL; Woodward, DF; Wang, JW; Clark, RL

2011-01-01

BACKGROUND AND PURPOSE The highly lipophilic acyl-sulphonamides L-798106 and L-826266 showed surprisingly slow antagonism of the prostanoid EP3 receptor system in guinea-pig aorta. Roles of affinity and lipophilicity in the onset kinetics of these and other prostanoid ligands were investigated. EXPERIMENTAL APPROACH Antagonist selectivity was assessed using a panel of human recombinant prostanoid receptor-fluorimetric imaging plate reader assays. Potencies/affinities and onset half-times of agonists and antagonists were obtained on guinea-pig-isolated aorta and vas deferens. n-Octanol-water partition coefficients were predicted. KEY RESULTS L-798106, L-826266 and the less lipophilic congener (DG)-3ap appear to behave as selective, competitive-reversible EP3 antagonists. For ligands of low to moderate lipophilicity, potency increments for EP3 and TP (thromboxane-like) agonism on guinea-pig aorta (above pEC50 of 8.0) were associated with progressively longer onset half-times; similar trends were found for TP and histamine H1 antagonism above a pA2 limit of 8.0. In contrast, L-798106 (EP3), L-826266 (EP3, TP) and the lipophilic H1 antagonists astemizole and terfenadine exhibited very slow onset rates despite their moderate affinities; (DG)-3ap (EP3) had a faster onset. Agonism and antagonism on the vas deferens EP3 system were overall much faster, although trends were similar. CONCLUSIONS AND IMPLICATIONS High affinity and high liphophilicity may contribute to the slow onsets of prostanoid ligands in some isolated smooth muscle preparations. Both relationships are explicable by tissue disposition under the limited diffusion model. EP3 antagonists used as research tools should have moderate lipophilicity. The influence of lipophilicity on the potential clinical use of EP3 antagonists is discussed. PMID:20973775

Response of three broccoli cultivars to salt stress, in relation to water status and expression of two leaf aquaporins.

PubMed

Muries, Beatriz; Carvajal, Micaela; Martínez-Ballesta, María Del Carmen

2013-05-01

The aim of this study was to compare differences in water relations in the leaves of three broccoli cultivars and differential induction of the expression of PIP2 aquaporin isoforms under salt stress. Although broccoli is known to be moderately tolerant to salinity, scarce information exists about the involvement of leaf aquaporins in its adaptation to salinity. Thus, leaf water relations, leaf cell hydraulic conductivity (Lpc), gas exchange parameters and the PIP2 expression pattern were determined for short- (15 h) and long- (15 days) term NaCl treatments. In the long term, the lower half-time of water exchange in the cells of cv. Naxos, compared with Parthenon and Chronos, and its increased PIP2 abundance may have contributed to its Lpc maintenance. This unmodified Lpc in cv. Naxos under prolonged salinity may have diluted NaCl in the leaves, as suggested by lower Na(+) concentrations in the leaf sap. By contrast, the increase in the half-time of water exchange and the lower PIP2 abundance in cvs. Chronos and Parthenon would have contributed to the reduced Lpc values. In cv. Parthenon, there were no differences between the ε values of control and salt-stressed plants; in consequence, cell turgor was enhanced. Also, the increases in BoPIP2;2 and BoPIP2;3 expression in cv. Chronos for the short-term NaCl treatment suggest that these isoforms are involved in osmotic regulation as downstream factors in this cultivar, in fact, in the short-term, Chronos had a significantly reduced osmotic potential and higher PIP2 isoforms expression.

Long-range correlations in an online betting exchange for a football tournament

NASA Astrophysics Data System (ADS)

Hardiman, Stephen J.; Richmond, Peter; Hutzler, Stefan

2010-10-01

We analyze the changes in the market odds of football matches in an online betting exchange, Betfair.com. We identify the statistical differences between the returns that occur when the game play is under way, which we argue are driven by match events, and the returns that occur during half-time, which we ascribe to a trader-driven noise. Furthermore, using detrended fluctuation analysis we identify anti-persistence (Hurst exponent H<0.5) in odds returns and long memory (H>0.5) in the volatilities, which we attribute to the trader-driven noise. The time series of trading volume are found to be short-memory processes.

Regeneration of Cation-Transport Capacity in HeLa Cell Membranes After Specific Blockade by Ouabain

PubMed Central

Vaughan, Gerald L.; Cook, John S.

1972-01-01

The cardiac glycoside, ouabain, inhibits alkali-cation transport in HeLa cells. It binds to 0.75 × 106 sites per cell, and the half-time for its dissociation is 16 hr. After partial blockade by ouabain, the cell generates new ouabain-binding sites, with total restoration of transport in 10% of a cell cycle(∼3 hr). This recovery requires protein synthesis and appears to be a response to altered cell-electrolyte content, since growth of cells in media with low K+ concentration enhances the titer of the transport enzyme in a fashion similar to the effect of ouabain. Totally blocked cells do not recover. PMID:4506784

Long-term lead elimination from plasma and whole blood after poisoning.

PubMed

Rentschler, Gerda; Broberg, K; Lundh, T; Skerfving, S

2012-04-01

Blood lead (B-Pb), one of the most used toxicological biomarker all kind, has serious limitations. Thus, the objective is to evaluate whether plasma lead (P-Pb) is more adequate. A long-term follow-up study of five cases of lead poisoning. P-Pb was analysed by inductively coupled plasma mass spectrometry. Kinetics after end of exposure was modelled. P-Pb at severe poisoning was about 20 μg/L; haematological effects at about 5 μg/L. Biological half-time of P-Pb was about 1 month; B-Pb decay was much slower. P-Pb is a valuable biomarker of exposure to and risk, particularly at high exposure.

Effect of temperature and initial dibutyl sulfide concentration in chloroform on its oxidation rate by ozone.

PubMed

Popiel, Stanisław; Nalepa, Tomasz; Dzierzak, Dorota; Stankiewicz, Romuald; Witkiewicz, Zygfryd

2008-09-15

A scheme of dibutyl sulfide (DBS) oxidation with ozone and generation of transitional products was determined in this study. The main identified intermediate product was dibutyl sulfoxide (DBSO), and the main end product of DBS oxidation was dibutyl sulfone (DBSO2). It was determined that for three temperatures: 0, 10 and 20 degrees C there was certain initial DBS concentration for which half-times observed in experimental conditions were equal and independent from temperature. Generation of phosgene and water as by-products was confirmed for the reaction of DBS with ozone in chloroform. Results of the described study allowed to present generalized mechanism of sulfide oxidation with ozone.

Correlation of echo-Doppler aortic valve regurgitation index with angiographic aortic regurgitation severity.

PubMed

Chen, Ming; Luo, Huai; Miyamoto, Takashi; Atar, Shaul; Kobal, Sergio; Rahban, Masoud; Brasch, Andrea V; Makkar, Rajendra; Neuman, Yoram; Naqvi, Tasneem Z; Tolstrup, Kirsten; Siegel, Robert J

2003-09-01

We assessed aortic regurgitation (AR) severity by utilizing multiple echo-Doppler variables in comparison with AR severity by aortic root angiography. Patients were divided into 3 groups: mild, moderate, and severe. An AR index (ARI) was developed, comprising 5 echocardiographic parameters: ratio of color AR jet height to left ventricular outlet flow diameter, AR signal density from continuous-wave Doppler, pressure half-time, left ventricular end-diastolic diameter, and aortic root diameter. There was a strong correlation between AR severity by angiography and the calculated echo-Doppler ARI (r = 0.84, p = 0.0001). As validated by aortic angiography, the ARI is an accurate reflection of AR severity.

Disposition and metabolism of 2,3-( UC)dichloropropene in rats after inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, J.A.; Medinsky, M.A.; Dutcher, J.S.

1985-01-01

2,3-Dichloropropene (2,3-DCP) is a constituent of some commercially available preplant soil fumigants for the control of plant parasitic nematodes. The purpose of this investigation was to determine the disposition and metabolism of 2,3-( UC)DCP in rats after inhalation. Male Fischer-344 rats were exposed nose-only to a vapor concentration of 250 nmol 2,3-( UC)DCP/liter air (7.5 ppm; 25C, 620 Torr) for 6 hr. Blood samples were taken during exposure, and urine, feces, expired air, and tissues were collected for up to 65 hr after exposure. Urinary excretion was the major route of elimination of UC (55% of estimated absorbed 2,3-DCP). Half-timemore » for elimination of UC in urine was 9.8 +/- 0.05 hr (anti x +/- SE). Half-time for elimination of UC feces (17% of absorbed 2,3-DCP) was 12.9 +/- 0.14 hr (anti x +/- SE). Approximately 1 and 3% of the estimated absorbed 2,3-( UC)DCP were exhaled as either 2,3-( UC)DCP or UCO2, respectively. Concentrations of UC in blood increased during 240 min of exposure, after which no further increases in blood concentration of UC were seen. UC was widely distributed in tissues analyzed after a 6-hr exposure of rats to 2,3-( UC)DCP. Urinary bladder (150 nmol/g), nasal turbinates (125 nmol/g), kidneys (84 nmol/g), small intestine (61 nmol/g), and liver (35 nmol/g) were tissues with the highest concentrations of UC immediately after exposure. Over 90% of the UC in tissues analyzed was 2,3-DCP metabolites. Half-times for elimination of UC from tissues examined ranged from 3 to 11 hr. The data from this study indicate that after inhalation 2,3-DCP is metabolized in tissues and readily excreted. 21 references. 2 figures, 4 tables.« less

Interaction of organophosphorus compounds with carboxylesterases in the rat.

PubMed

Jokanović, M; Kosanović, M; Maksimović, M

1996-01-01

Carboxylesterases (CarbE) are involved in detoxication of organophosphorus compounds (OPC) through two mechanisms: hydrolysis of ester bonds in OPC which contain them and binding of OPC at the active site of CarbE which reduces the amount of OPC available for acetylcholinesterase inhibition. This study of the interaction of rat plasma and liver CarbE with dichlorvos, soman and sarin in vitro and in vivo was undertaken in order to contribute to better understanding of the role of CarbE in detoxication of OPC. The results obtained have shown that inhibitory potency (I50) of dichlorvos, sarin and soman towards rat liver CarbE was 0.2 microM, 0.5 microM and 4.5 microM, respectively, for 20-min incubation at 25 degrees C. Second-order rate constants (k(a)) for liver CarbE inhibition were 2.3 x 10(5) M-1 min-1, 6.9 x 10(4) M-1 min-1 and 1.1 x 10(4) M-1 min-1 for dichlorvos, sarin and soman, respectively. The corresponding values for plasma CarbE could not be calculated because of dominant spontaneous reactivation of inhibited CarbE. CarbE inhibited with these OPC in vitro spontaneously reactivate with half-times of 18, 143 and 497 min for sarin, dichlorvos and soman in plasma and 111, 163 and 297 min for sarin, soman and dichlorvos in liver, respectively. These results were also confirmed in experiments in vivo in which rats were subcutaneously treated with 0.5 LD50 of these agents. The half-times of spontaneous reactivation of rat plasma CarbE in vivo were 1.2, 2.0 and 2.7 h for dichlorvos, sarin and soman, respectively. These findings have changed current understanding of the mechanism of interaction of CarbE with OPC and involvement of the enzymes in detoxication of OPC, suggesting an active and important role of the enzymes in metabolic conversions of OPC to their less toxic metabolites.

A kinematic model to estimate effective dose of radioactive substances in a human body

NASA Astrophysics Data System (ADS)

Sasaki, S.; Yamada, T.

2013-05-01

The great earthquake occurred in the north-east area in Japan in March 11, 2011. Facility system to control Fukushima Daiichi nuclear power station was completely destroyed by the following giant tsunami. From the damaged reactor containment vessels, an amount of radioactive substances had leaked and diffused in the vicinity of this station. Radiological internal exposure became a serious social issue both in Japan and all over the world. The present study provides an easily understandable, kinematic-based model to estimate the effective dose of radioactive substances in a human body by simplifying the complicated mechanism of metabolism. International Commission on Radiological Protection (ICRP) has developed a sophisticated model, which is well-known as a standard method to calculate the effective dose for radiological protection. However, owing to that ICRP method is fine, it is rather difficult for non-professional people of radiology to gasp the whole images of the movement and the influences of radioactive substances in a human body. Therefore, in the present paper we propose a newly-derived and easily-understandable model to estimate the effective dose. The present method is very similar with the traditional and conventional tank model in hydrology. Ingestion flux of radioactive substances corresponds to rain intensity and the storage of radioactive substances to the water storage in a basin in runoff analysis. The key of the present method is to estimate the energy radiated in the radioactive nuclear disintegration of an atom by using classical theory of β decay and special relativity for various kinds of radioactive atoms. The parameters used in this model are only physical half-time and biological half-time, and there are no operational parameters or coefficients to adjust our theoretical runoff to ICRP. Figure shows the time-varying effective dose with ingestion duration, and we can confirm the validity of our model. The time-varying effective dose with ingestion duration

Kinetics of Recovery of the Dark-adapted Salamander Rod Photoresponse

PubMed Central

Nikonov, S.; Engheta, N.; Pugh, E.N.

1998-01-01

The kinetics of the dark-adapted salamander rod photocurrent response to flashes producing from 10 to 105 photoisomerizations (Φ) were investigated in normal Ringer's solution, and in a choline solution that clamps calcium near its resting level. For saturating intensities ranging from ∼102 to 104 Φ, the recovery phases of the responses in choline were nearly invariant in form. Responses in Ringer's were similarly invariant for saturating intensities from ∼103 to 104 Φ. In both solutions, recoveries to flashes in these intensity ranges translated on the time axis a constant amount (τc) per e-fold increment in flash intensity, and exhibited exponentially decaying “tail phases” with time constant τc. The difference in recovery half-times for responses in choline and Ringer's to the same saturating flash was 5–7 s. Above ∼104 Φ, recoveries in both solutions were systematically slower, and translation invariance broke down. Theoretical analysis of the translation-invariant responses established that τc must represent the time constant of inactivation of the disc-associated cascade intermediate (R*, G*, or PDE*) having the longest lifetime, and that the cGMP hydrolysis and cGMP-channel activation reactions are such as to conserve this time constant. Theoretical analysis also demonstrated that the 5–7-s shift in recovery half-times between responses in Ringer's and in choline is largely (4–6 s) accounted for by the calcium-dependent activation of guanylyl cyclase, with the residual (1–2 s) likely caused by an effect of calcium on an intermediate with a nondominant time constant. Analytical expressions for the dim-flash response in calcium clamp and Ringer's are derived, and it is shown that the difference in the responses under the two conditions can be accounted for quantitatively by cyclase activation. Application of these expressions yields an estimate of the calcium buffering capacity of the rod at rest of ∼20, much lower than previous estimates. PMID:9417132

Effect-site half-time for burst suppression is longer than for hypnosis during anaesthesia with sevoflurane.

PubMed

Kennedy, R R; Minto, C; Seethepalli, A

2008-01-01

The relationship between measures of drug effect such as bispectral index (BIS) and end-tidal (ET) levels of anaesthetic agents is described by the 'effect site equilibrium half-time', t(1/2)(ke0). There are limited data available on sevoflurane t(1/2)(ke0) during routine anaesthesia and surgery. Preliminary observations suggested t(1/2)(ke0) for the degree of hypnosis as estimated by BIS is different from that for burst suppression of the electroencephalograph, occurring at 'deep' levels of anaesthesia. This study aimed to determine and compare t(1/2)(ke0) for these two 'effects'. Large changes in ET sevoflurane were produced in 13 subjects during surgery. ET sevoflurane, BIS, and burst suppression ratio (BSR) were recorded every 10 s. Data were divided into epochs with BIS>30 (BIS) or with BSR>10% (burst suppression). Using a non-parametric modelling technique, t(1/2)(ke0) was determined for each epoch. There were 36 'BIS' and 20 burst suppression zones. Mean (sd) t(1/2)(ke0) for BIS was 3.48 (1.12) min and for BSR 9.9 (6.4) min. In all subjects, t(1/2)(ke0) BIS

Particle clearance and histopathology in lungs of C3H/HeJ mice administered beryllium/copper alloy by intratracheal instillation.

PubMed

Benson, J M; Holmes, A M; Barr, E B; Nikula, K J; March, T H

2000-08-01

Beryllium/copper (BeCu) alloys are commonly used in the electronics, automotive, consumer, defense, and aerospace industries. Some individuals exposed occupationally to BeCu alloys have developed chronic beryllium disease. However, little is known of the toxicity and fate of BeCu alloys in the respiratory tract. To begin to address this question, we investigated the pulmonary toxicity and clearance of BeCu alloy (2% Be; 98% Cu) in mice. Groups of 40 female C3H/HeJ mice were administered 12.5, 25, and 100 microg BeCu alloy or 2 and 8 microg Be metal by intratracheal instillation. Mice were sacrificed at 1 h and 1, 7, 14, and 28 days postinstillation. Left lungs were evaluated for histopathological change. Right lungs were analyzed for Be and Cu content. Twenty-five percent of the high-dose BeCu mice and 7.5% of the mid-dose BeCu mice died within 24 h of dosing. Acute pulmonary lesions included acute alveolitis and interstitial inflammation. Type II epithelial cell hyperplasia and centriacinar fibrosis were present by 7 days after dosing. Lesions persisted through 28 days after instillation. No lesions attributable to alloy exposure were present in liver or kidney. Be metal instillation caused no deaths and minimal pulmonary changes over the time studied, indicating that the pulmonary lesions were due to Cu rather than Be. Cu cleared the lung with a half-time of 0. 5-2 days. Be cleared with a half-time of several weeks or longer. Results of this study suggest that exposure to BeCu alloy is more acutely toxic to lung than Be metal. The results of tissue analyses also indicate that, while the Cu component of the alloy clears the lung rapidly, Be is retained and may accumulate upon repeated exposure.

Lung retention and metabolic fate of inhaled benzo(a)pyrene associated with diesel exhaust particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, J.D.; Wolff, R.K.; Kanapilly, G.M.

The effect of ultrafine, insoluble, carrier particles on the lung retention and metabolic fate of inhaled PAHs was investigated with a radiolabeled model PAH, (/sup 3/H)benzo(a)pyrene (/sup 3/H-BaP). Fischer-344 rats were exposed (30 min) by nose-only inhalation to /sup 3/H-BaP adsorbed (approximately 0.1% by mass) onto diesel engine exhaust particles. The total mass concentration of these aerosols was 4-6 micrograms/liter of air with a mass median diameter of 0.14 micron. Lung clearance of the inhaled particle-associated /sup 3/H radioactivity occurred in two phases. The initially rapid clearance of this inhaled radiolabel had a half-time of less than 1 hr. Themore » second, long-term component of lung clearance had a half-time of 18 +/- 2 days and represented 50 +/- 2% of the /sup 3/H radioactivity that had initially deposited in lungs. In contrast, previous inhalation studies with a pure /sup 3/H-BaP aerosol showed that greater than 99% of the /sup 3/H radioactivity deposited in lungs was cleared within 2 hr after exposure. By HPLC analysis, the majority of diesel soot-associated /sup 3/H radioactivity retained in lungs was BaP (65-76%) with smaller amounts of BaP-phenol (13-17%) and BaP-quinone (5-18%) metabolites also being detected. No other metabolites of BaP were detected in lungs of exposed rats. Tissue distribution and excretion patterns of /sup 3/H radioactivity were qualitatively similar to previous inhalation studies with /sup 3/H-BaP coated Ga2O3 aerosols. These findings suggest that inhaled PAHs may be retained in lungs for a greater period of time when these compounds are associated with diesel engine exhaust particles. These results may have significant implications for the health risks that may be involved with human exposure to particle-associated organic pollutants.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Šefl, Martin, E-mail: martin.sefl@gmail.com; Kyriakou, Ioanna; Emfietzoglou, Dimitris, E-mail: demfietz@cc.uoi.gr

Purpose: To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. Methods: The instantaneous-uptake model of O’Donoghue [“The impact of tumor cell proliferation in radioimmunotherapy,” Cancer 73, 974–980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). Results: Surviving fractions aremore » calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1–24 h, extrapolated initial dose-rates 0.5–1 Gy h{sup −1}, and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy{sup −1}. It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. Conclusions: The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.« less

STS-27 crew poses for inflight portrait on forward flight deck with football

NASA Technical Reports Server (NTRS)

1988-01-01

With WILSON NFL football freefloating in front of them, STS-27 astronauts pose on Atlantis', Orbiter Vehicle (OV) 104's, forward flight deck for inflight crew portrait. Crewmembers, wearing blue mission t-shirts, are (left to right) Commander Robert L. Gibson, Mission Specialist (MS) Richard M. Mullane, MS Jerry L. Ross, MS William M. Shepherd, and Pilot Guy S. Gardner. Forward flight deck overhead control panels are visible above crewmembers, commanders and pilots seats in front of them, and forward windows behind them. An auto-set 35mm camera mounted on the aft flight deck was used to take this photo. The football was later presented to the National Football League (NFL) at halftime of the Super Bowl in Miami.

An age-specific biokinetic model for iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leggett, Richard Wayne

This study reviews age-specific biokinetic data for iodine in humans and extends to pre-adult ages the baseline parameter values of the author’s previously published model for systemic iodine in adult humans. Compared with the ICRP’s current age-specific model for iodine introduced in Publication 56 (1989), the present model provides a more detailed description of the behavior of iodine in the human body; predicts greater cumulative (integrated) activity in the thyroid for short-lived isotopes of iodine; predicts similar cumulative activity in the thyroid for isotopes with half-time greater than a few hours; and, for most iodine isotopes, predicts much greater cumulativemore » activity in salivary glands, stomach wall, liver, and kidneys.« less

An age-specific biokinetic model for iodine

DOE PAGES

Leggett, Richard Wayne

2017-10-26

This study reviews age-specific biokinetic data for iodine in humans and extends to pre-adult ages the baseline parameter values of the author’s previously published model for systemic iodine in adult humans. Compared with the ICRP’s current age-specific model for iodine introduced in Publication 56 (1989), the present model provides a more detailed description of the behavior of iodine in the human body; predicts greater cumulative (integrated) activity in the thyroid for short-lived isotopes of iodine; predicts similar cumulative activity in the thyroid for isotopes with half-time greater than a few hours; and, for most iodine isotopes, predicts much greater cumulativemore » activity in salivary glands, stomach wall, liver, and kidneys.« less

UK nuclear medicine survey, 1992-93.

PubMed

Elliott, A T; Elliott, F M; Shields, R A

1996-01-01

A postal survey of UK nuclear medicine departments was undertaken to collate information on equipment, numbers of procedures and staffing levels for the years 1992 and 1993. It was estimated that there are 235 sites undertaking nuclear medicine, the total number of procedures performed being some 490,000 in 1993 compared with 430,000 in 1989. Informal investigation suggests that the increase is due to greater usage of myocardial perfusion and lung ventilation/perfusion studies. Wide variations were noted in staffing levels, with only 22% of departments having medical cover of half-time equivalent or better: over 30% of departments have less than one consultant session per week. Approximately 20% of departments claimed to have no physics input, with a further 20% having less than one session per week.

Design and analysis of linear cascade DNA hybridization chain reactions using DNA hairpins

NASA Astrophysics Data System (ADS)

Bui, Hieu; Garg, Sudhanshu; Miao, Vincent; Song, Tianqi; Mokhtar, Reem; Reif, John

2017-01-01

DNA self-assembly has been employed non-conventionally to construct nanoscale structures and dynamic nanoscale machines. The technique of hybridization chain reactions by triggered self-assembly has been shown to form various interesting nanoscale structures ranging from simple linear DNA oligomers to dendritic DNA structures. Inspired by earlier triggered self-assembly works, we present a system for controlled self-assembly of linear cascade DNA hybridization chain reactions using nine distinct DNA hairpins. NUPACK is employed to assist in designing DNA sequences and Matlab has been used to simulate DNA hairpin interactions. Gel electrophoresis and ensemble fluorescence reaction kinetics data indicate strong evidence of linear cascade DNA hybridization chain reactions. The half-time completion of the proposed linear cascade reactions indicates a linear dependency on the number of hairpins.

Immobilization of l-Asparaginase on Carrier Materials: A Comprehensive Review.

PubMed

Ulu, Ahmet; Ates, Burhan

2017-06-21

There are two major applications of l-asparaginase (L-ASNase): leukemia therapy and the food industry. Especially, its chemotherapeutic effect has attracted interest from the scientific community and individual scientists. Therefore, to protect the intrinsic activity and half-time of L-ASNase, several carriers and immobilization techniques for immobilization of L-ASNase have been described in articles. Unfortunately, a comprehensive review about immobilization of L-ASNase has not been written until now. In this review, we have thoroughly discussed the carriers for L-ASNase by illustrating immobilization findings including both past and present applications. In addition, we have revealed advantages and disadvantages of immobilized enzyme and related it to free form. We believe that this review will not only provide background information, but also guide future developments.

“Nano-Ginseng” for Enhanced Cytotoxicity AGAINST Cancer Cells

PubMed Central

Zhu, Weiyan; Si, Chuanling; Lei, Jiandu

2018-01-01

Panax ginseng has high medicinal and health values. However, the various and complex components of ginseng may interact with each other, thus reducing and even reversing therapeutic effects. In this study, we designed and fabricated a novel “nano-ginseng” with definite ingredients, ginsenoside Rb1/protopanaxadiol nanoparticles (Rb1/PPD NPs), completely based on the protopanaxadiol-type extracts. The optimized nano-formulations demonstrated an appropriate size (~110 nm), high drug loading efficiency (~96.8%) and capacity (~27.9 wt %), long half-time in systemic circulation (nine-fold longer than free PPD), better antitumor effects in vitro and in vivo, higher accumulation at the tumor site and reduced damage to normal tissues. Importantly, this process of “nano-ginseng” production is a simple, scalable, green economy process. PMID:29473838

Fallout strontium-90 and cesium-137 in northern Alaskan ecosystems during 1959--1970

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, Wayne C.

1973-05-01

Cycling routes, rates of transport, and resultant concentrations of the fallout radionuclides 90Sr and 137Cs in northern Alaskan ecosystems were defined during the period 1959 to 1970. Radiochemical analysis of extensive samples of biota and whole-body counting of 137Cs in Eskimo and Indian ethnic groups were related to ecological principles, especially the concept of trophic niche, which elucidated the observed patterns of radionuclide concentrations. Experiments involving Sr and Cs radioisotopes applied to natural Cladonia-- Cetraria lichen carpets yielded effective half-times of 1.O to 1.6 years for Sr and more than 10 years for Cs. Direct and indirect estimates of 131Csmore » half-times in Eskimos on a caribou meat diet were made by dietary manipulation and by relating dietary 137Cs intake and resultant change between periodic whole body counts. Effective half- times of 70 days for adults (more than 21 years old) and minors (14 to 20 years old) and of 45 days for children (less than 14 years old) were found. Suitable mathematical models were used to compute lichen forage ingestion rates of free- ranging adult caribou (4.5 to 5.0 kg dry weight per day), caribou meat ingestion rates of Anaktuvuk Pass residents (up to 2 kg wet weight per day for men), and 90Sr body burdens of Anaktuvuk Pass residents during the period 1952 to 1968 (maximum value of 8 nCi in adult males during late 1966 to early 1967). Special emphasis was made of cultural influences upon the food-gathering patterns of the native peoples studied. Culture change, especially in the form of food stamps, welfare payments, acquisition of snowmobiles, and improved housing was documented throughout the study and noticeably reduced the radionuclide accumulations. Total radiation dose rates to the Anaktuvuk Pass adult population were estimated to be about 100 mrad/year from natural sources, 60 to 140 mrad/year from 137Cs body burdens, and 20 to 130 mrad/year from 90Sr body burdens.« less

Pulmonary responses in current smokers and ex-smokers following a two hour exposure at rest to clean air and fine ambient air particles

PubMed Central

2013-01-01

Background Increased susceptibility of smokers to ambient PM may potentially promote development of COPD and accelerate already present disease. Objectives To characterize the acute and subacute lung function response and inflammatory effects of controlled chamber exposure to concentrated ambient fine particles (CAFP) with MMAD ≤ 2.5 microns in ex-smokers and lifetime smokers. Methods Eleven subjects, aged 35–74 years, came to the laboratory 5 times; a training day and two exposure days separated by at least 3 weeks, each with a post-exposure visit 22 h later. Double-blind and counterbalanced exposures to “clean air” (mean 1.5 ± 0.6 μg/m3) or CAFP (mean 108.7 ± 24.8 μg/m3 ) lasted 2 h with subjects at rest. Results At 3 h post-exposure subjects’ DTPA clearance half-time significantly increased by 6.3 min per 100 μg/m3 of CAFP relative to “clean air”. At 22 h post-exposure they showed significant reduction of 4.3% per 100 μg/m3 in FEV1 and a significant DLCO decrease by 11.1% per 100 μg/m3 of CAFP relative to “clean air”. At both 3 h and 22 h the HDL cholesterol level significantly decreased by 4.5% and 4.1%, respectively. Other blood chemistries and markers of lung injury, inflammation and procoagulant activity were within the normal range of values at any condition. Conclusions The results suggest that an acute 2 h resting exposure of smokers and ex-smokers to fine ambient particulate matter may transiently affect pulmonary function (spirometry and DLCO) and increase DTPA clearance half-time. Except for a post exposure decrease in HDL no other markers of pulmonary inflammation, prothrombotic activity and lung injury were significantly affected under the conditions of exposure. PMID:24245863

Combining the LKB NTCP model with radiosensitivity parameters to characterize toxicity of radionuclides based on a multiclonogen kidney model: a theoretical assessment.

PubMed

Lin, Hui; Jing, Jia; Xu, Liangfeng; Wu, Dongsheng; Xu, Yuanying

2012-06-01

The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model is often used to estimate the damage level to normal tissue. However, it does not manifestly involve the influence of radiosensitivity parameters. This work replaces the generalized mean equivalent uniform dose (gEUD) with the equivalent uniform dose (EUD) in the LKB model to investigate the effect of a variety of radiobiological parameters on the NTCP to characterize the toxicity of five types of radionuclides. The dose for 50 % complication probability (D (50)) is replaced by the corresponding EUD for 50 % complication probability (EUD(50)). The properties of a variety of radiobiological characteristics, such as biologically effective dose (BED), NTCP, and EUD, for five types of radioisotope ((131)I, (186)Re, (188)Re, (90)Y, and (67)Cu) are investigated by various radiosensitivity parameters such as intrinsic radiosensitivity α, alpha-beta ratio α/β, cell repair half-time, cell mean clonogen doubling time, etc. The high-energy beta emitters ((90)Y and (188)Re) have high initial dose rate and mean absorbed dose per injected activity in kidney, and their kidney toxicity should be of greater concern if they are excreted through kidneys. The radiobiological effect of (188)Re changes most sharply with the radiobiological parameters due to its high-energy electrons and very short physical half-life. The dose for a probability of 50% injury within 5y (D (50/5)) 28 Gy for whole-kidney irradiation should be adjusted according to different radionuclides and different radiosensitivity of individuals. The D (50/5) of individuals with low α/β or low α, or low biological clearance half-time, will be less than 28 Gy. The 50 % complication probability dose for (67)Cu and (188)Re could be 25 Gy and 22 Gy. The same mean absorbed dose generally corresponds to different degrees of damage for tissues of different radiosensitivity and different radionuclides. The influence of various radiobiological parameters should be taken into consideration in the NTCP model.

Report on computation of repetitive hyperbaric-hypobaric decompression tables

NASA Technical Reports Server (NTRS)

Edel, P. O.

1975-01-01

The tables were constructed specifically for NASA's simulated weightlessness training program; they provide for 8 depth ranges covering depths from 7 to 47 FSW, with exposure times of 15 to 360 minutes. These tables were based up on an 8 compartment model using tissue half-time values of 5 to 360 minutes and Workmanline M-values for control of the decompression obligation resulting from hyperbaric exposures. Supersaturation ratios of 1.55:1 to 2:1 were used for control of ascents to altitude following such repetitive dives. Adequacy of the method and the resultant tables were determined in light of past experience with decompression involving hyperbaric-hypobaric interfaces in human exposures. Using these criteria, the method showed conformity with empirically determined values. In areas where a discrepancy existed, the tables would err in the direction of safety.

Modes of Hypotensive Action of Dihydroquercetin in Arterial Hypertension.

PubMed

Plotnikov, M B; Aliev, O I; Sidekhmenova, A V; Shamanaev, A Yu; Anishchenko, A M; Nosarev, A V; Pushkina, E A

2017-01-01

We studied the effect of dihydroquercetin (20 mg/kg/day intragastrically for 6 weeks) on mean BP and macro- and microrheological blood parameters in hypertensive SHR rats; in vitro effect of dihydroquercetin on the tone in thoracic aorta rings isolated from hypertensive SHR rats were also examined. At the end of the treatment course, the mean BP in the experimental rats decreased by 11%; the left ventricular mass index by 2%, and whole blood viscosity by 7-10% in comparison with control SHR rats; erythrocyte aggregation half-time increased by 15%; plasma viscosity, hematocrit, and erythrocyte deformability did not change. In in vitro experiments, dihydroquercetin (10 -8 -10 -6 M) induced relaxation of the isolated thoracic aorta rings in a dose-dependent manner. Hence, the antihypertensive effect of dihydroquercetin results from the decrease in blood viscosity and vasodilation.

Solid Test Meal to Measure the Gastric Emptying with Magnetogastrography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reynaga-Ornelas, M. G.; Roca-Chiapas, J. M. de ls; Cordova-Fraga, T.

2008-08-11

The gastric emptying is the time of evacuating the food ingested from the stomach to the duodenum in a controlled rate. Diverse studies express the results of the gastric emptying in form of half-time (t{sub 1/2}). The Magnetogastrography (MGG) is a biomagnetic technique that has the advantage of not being invasive, radiation free and does not interfere with the privacy of the subject. The objective was to analyze the magnetic signal of magnetic tracers mixed in a solid food to measure gastric emptying using Magnetogastrography. The ingested test meal displayed a magnetic signal, which served to obtain the signal registeredmore » by the fluxgate and the peristaltic contractions could be calculated while the stomach was emptying. The solid food product developed results to work satisfactorily in magnetogastrography.« less

Man-made mineral fiber hazardous properties assessment using transgenic rodents: example of glass fiber testing.

PubMed

Bottin, M C; Vigneron, J C; Rousseau, R; Micillino, J C; Eypert-Blaison, C; Kauffer, E; Martin, P; Binet, S; Rihn, B H

2003-09-01

Transgenic BigBlue rats were exposed to CM 44 glass fibers (6.3 mg/m3) by nose only, 6 h/day for 5 days. Two endpoints were examined 1, 3, 14, 28, and 90 days following exposure: fiber biopersistence and mutations in lung DNA. The half-time of the fibers >20 microm was 12.8 days, and mutant frequencies of control and exposed rats were similar across all time points. The mutation spectra of both series were similar after 28 days of fixation time. These results showed that a glass fiber with a high clearance in the lung seems to not present any significant effect on mutagenesis on lung DNA and are in marked contrast to results for asbestos, which caused a twofold mutant frequency increase as described in a previous study.

Calcium transients recorded with arsenazo III in the presynaptic terminal of the squid giant synapse.

PubMed

Miledi, R; Parker, I

1981-05-22

Transient changes in free intracellular Ca2+ concentration were monitored in the presynaptic terminal of the giant synapse of the squid, by means of the Ca2+-sensitive dye arsenazo III. Calibration experiments showed a linear relation between the amount of Ca2+ injected by iontophoresis into the terminal, and the peak size of the arsenazo light absorbance record. A light signal could be detected on tetanic stimulation of the presynaptic axon bathed in sea water containing 45 mM Ca2+. During a 1 s tetanus the light signal rose approximately linearly, even though transmitter release declined rapidly and the light signal subsequently declined with a half-time of 2-6 s. The Ca2+ transient elicited by single nerve impulses was recorded by signal averaging, and showed a time course very much slower than the duration of transmitter release.

Peripheral muscle ergoreceptors and ventilatory response during exercise recovery in heart failure.

PubMed

Francis, N; Cohen-Solal, A; Logeart, D

1999-03-01

Recent studies have suggested that the increased ventilatory response during exercise in patients with chronic heart failure was related to the activation of muscle metaboreceptors. To address this issue, 23 patients with heart failure and 7 normal subjects performed arm and leg bicycle exercises with and without cuff inflation around the arms or the thighs during recovery. Obstruction slightly reduced ventilation and gas exchange variables at recovery but did not change the kinetics of recovery of these parameters compared with nonobstructed recovery: half-time of ventilation recovery was 175 +/- 54 to 176 +/- 40 s in patients and 155 +/- 66 to 127 +/- 13 s in controls (P < 0.05, patients vs. controls, not significant within each group from baseline to obstructed recovery). We conclude that muscle metaboreceptor activation does not seem to play a role in the exertion hyperventilation of patients with heart failure.

Base-enhanced catalytic water oxidation by a carboxylate–bipyridine Ru(II) complex

DOE PAGES

Song, Na; Concepcion, Javier J.; Binstead, Robert A.; ...

2015-04-06

In aqueous solution above pH 2.4 with 4% (vol/vol) CH 3CN, the complex [Ru II(bda)(isoq) 2] (bda is 2,2'-bipyridine-6,6'-dicarboxylate; isoq is isoquinoline) exists as the open-arm chelate, [Ru II(CO 2-bpy-CO 2 $-$)(isoq) 2(NCCH 3)], as shown by 1H and 13C-NMR, X-ray crystallography, and pH titrations. Rates of water oxidation with the open-arm chelate are remarkably enhanced by added proton acceptor bases, as measured by cyclic voltammetry (CV). In 1.0 M PO 4 3–, the calculated half-time for water oxidation is ~7 μs. In conclusion, the key to the rate accelerations with added bases is direct involvement of the buffer basemore » in either atom–proton transfer (APT) or concerted electron–proton transfer (EPT) pathways.« less

Decrease of Nitrate Reductase Activity in Spinach Leaves during a Light-Dark Transition 1

PubMed Central

Riens, Burgi; Heldt, Hans Walter

1992-01-01

In leaves of spinach plants (Spinacia oleracea L.) performing CO2 and NO3− assimilation, at the time of sudden darkening, which eliminates photosystem I-dependent nitrite reduction, only a minor temporary increase of the leaf nitrite content is observed. Because nitrate reduction does not depend on redox equivalents generated by photosystem I activity, a continuation of nitrate reduction after darkening would result in a large accumulation of nitrite in the leaves within a very short time, which is not observed. Measurements of the extractable nitrate reductase activity from spinach leaves assayed under standard conditions showed that in these leaves the nitrate reductase activity decreased during darkening to 15% of the control value with a half-time of only 2 minutes. Apparently, in these leaves nitrate reductase is very rapidly inactivated at sudden darkness avoiding an accumulation of the toxic nitrite in the cells. PMID:16668679

"Deflategate": Time, Temperature, and Moisture Effects on Football Pressure

NASA Astrophysics Data System (ADS)

Blumenthal, Jack; Beljak, Lauren; Macatangay, Dahlia-Marie; Helmuth-Malone, Lilly; McWilliams, Catharina; Raptis, Sofia

2016-09-01

In a recent paper in TPT, DiLisi and Rarick used the National Football League "Deflategate" controversy to introduce to physics students the physics of a bouncing ball. In this paper, we measure and analyze the environmental effects of time, ambient temperature, and moisture on the internal pressure of an NFL football. We focus on the rate of pressure recovery that occurs when a cold football (either wet or dry) is returned to the warm locker room environment where the pressure was initially measured. Both studies stem from the so-called NFL "Deflategate" controversy in which footballs that initially met a minimum internal pressure requirement were rechecked at halftime of the AFC Championship game, and in some cases were reported to have fallen below the minimum pressure requirement. The question is whether the pressure changes were due to environmental exposure or rather to some air being released from the balls, or both.

Simple preparation of Fenton catalyst@bacterial cellulose for waste water treatment

NASA Astrophysics Data System (ADS)

Wibowo, Arie; Febi Indrawan, Radian; Triadhi, Untung; Hasdi Aimon, Akfiny; Iskandar, Ferry; Ardy, Husaini

2018-02-01

Heterogeneous fenton catalyst is one of the attractive technologies for destruction of persistent and non-biodegradable pollutant in wastewater, because it can be used in wide range of pH and recyclable. Herein, commercial bacterial celluloses (BCs) were used as an alternative support of fenton catalyst to improve their catalytic activity. Scanning Electron Microscope (SEM) observations indicated that the presence of BCs and decreasing precursor concentration might promote formation of smaller particle sizes of catalyst from 3.5 μm of bare catalyst to 0.7 μm of catalyst@BC. UV-vis measurement showed that fast degradation of dyes with half-time degradation at around 25 min was observed in sample using catalyst@BCs with precursor concentration of 0.01 M. Successful preparation of heterogeneous fenton catalyst with smaller particle size and better catalytic activity is important for their application in wastewater treatment.

Clinical, echocardiographic, and Doppler imaging characteristics of mitral valve stenosis in two dogs.

PubMed

Fox, P R; Miller, M W; Liu, S K

1992-11-15

Mitral stenosis was diagnosed noninvasively by echocardiography and Doppler imaging in 2 Bull Terriers. Two-dimensional echocardiography revealed severe atrial and moderate left ventricular dilatation; severely reduced mitral valve opening excursion; doming of the cranial mitral valve leaflet into the left ventricle during diastole; thickened, nodular cranial mitral valve leaflets; and reduced mitral valve orifice. M-mode echocardiographic findings additionally indicated greatly diminished mitral valve E to F slope and abnormal caudal mitral valve leaflet motion. Color flow Doppler imaging revealed bright bursts of color with aliasing originating from the stenotic mitral valve orifice, extending into the left atrium during systole, and into the left atrium during diastole. Spectral Doppler recordings revealed transvalvular mitral valve gradients and prolonged pressure half-times. Necropsy performed on 1 dog revealed extremely thickened, nodular, and stiff mitral valves with short, thickened, and fused chordae tendineae. The diagnosis of mitral valve stenosis was easily facilitated with diagnostic ultrasonography.

Base-enhanced catalytic water oxidation by a carboxylate–bipyridine Ru(II) complex

PubMed Central

Song, Na; Concepcion, Javier J.; Binstead, Robert A.; Rudd, Jennifer A.; Vannucci, Aaron K.; Dares, Christopher J.; Coggins, Michael K.; Meyer, Thomas J.

2015-01-01

In aqueous solution above pH 2.4 with 4% (vol/vol) CH3CN, the complex [RuII(bda)(isoq)2] (bda is 2,2′-bipyridine-6,6′-dicarboxylate; isoq is isoquinoline) exists as the open-arm chelate, [RuII(CO2-bpy-CO2−)(isoq)2(NCCH3)], as shown by 1H and 13C-NMR, X-ray crystallography, and pH titrations. Rates of water oxidation with the open-arm chelate are remarkably enhanced by added proton acceptor bases, as measured by cyclic voltammetry (CV). In 1.0 M PO43–, the calculated half-time for water oxidation is ∼7 μs. The key to the rate accelerations with added bases is direct involvement of the buffer base in either atom–proton transfer (APT) or concerted electron–proton transfer (EPT) pathways. PMID:25848035

Effect of iodine disinfection products on higher plants

NASA Technical Reports Server (NTRS)

Janik, D.; Macler, B.; Macelroy, R. D.; Thorstenson, Y.; Sauer, R.

1989-01-01

Iodine is used to disinfect potable water on United States spacecraft. Iodinated potable water will likely be used to grow plants in space. Little is known about the effects of iodine disinfection products on plants. Seeds of select higher plants were germinated in water iodinated using the Shuttle Microbial Check Valve, and water to which measured amounts of iodine was added. Percent germination was decreased in seeds of most species germinated in iodinated water. Beans were most affected. Germination rates, determined from germination half-times, were decreased for beans germinated in iodinated water, and water to which iodide was added. Development was retarded and rootlets were conspicuously absent in bean and several other plant species germinated in iodinated water. Iodide alone did not elicit these responses. Clearly iodine disinfection products can affect higher plants. These effects must be carefully considered for plant experimentation and cultivation in space, and in design and testing of closed environmental life support systems.

Electrosprayed synthesis of red-blood-cell-like particles with dual modality for magnetic resonance and fluorescence imaging.

PubMed

Hayashi, Koichiro; Ono, Kenji; Suzuki, Hiromi; Sawada, Makoto; Moriya, Makoto; Sakamoto, Wataru; Yogo, Toshinobu

2010-11-05

Red blood cells (RBCs) are able to avoid filtration in the spleen to prolong their half-time in the body because of their flexibility and unique shape, or a concave disk with diameter of some 10 μm. In addition, they can flow through capillary blood vessels, which are smaller than the diameter of RBCs, by morphing into a parachute-like shape. In this study, flexible RBC-like polymer particles are synthesized by electrospraying based on electrospinning. Furthermore, magnetite nanoparticles and fluorescent dye are encapsulated in the particles via in situ hydrolysis of an iron-organic compound in the presence of celluloses. The superparamagnetic behavior of the particles is confirmed by low-temperature magnetic measurements. The particles exhibited not only a dark contrast in magnetic resonance imaging (MRI), but also effective fluorescence. The RBC-like particles with flexibility are demonstrated to have a dual-modality for MRI and fluorescence imaging.

Obtaining a critical care pharmacist position: a marketing case study.

PubMed

Stratton, T P; Wu, B; Nakagawa, R S

1993-06-01

Marketing theory is used to explain how Pharmacy Department managers at a Vancouver-area hospital secured a new ICU pharmacist position in a period of severe fiscal constraint. Market segmentation, target marketing and pull marketing strategy were combined to obtain support for the new position. Improved drug information services for ICU nurses were promoted to Nursing Administration and enhanced pharmacotherapy monitoring was promoted to the two critical care physicians primarily responsible for patient care in the ICU. These physicians and Nursing Administration voiced their support for the new position to the V.P. of Nursing (the functional officer for Pharmacy), who then promoted the new position to Hospital Administration. A half-time DUR commitment by the ICU pharmacist was offered to Hospital Administration, expanding this already successful service and guaranteeing cost recovery for the new position. Hospital Administration approved the new ICU clinical pharmacist position in a budget which saw other hospital departments lose several positions.

Prediction of iodine-131 biokinetics and radiation doses from therapy on the basis of tracer studies: an important question for therapy planning in nuclear medicine.

PubMed

Willegaignon, José; Pelissoni, Rogério A; Lima, Beatriz C G D; Sapienza, Marcelo T; Coura-Filho, George B; Buchpiguel, Carlos A

2016-05-01

This study aimed to present a comparison of iodine-131 (I) biokinetics and radiation doses to red-marrow (rm) and whole-body (wb), following the administration of tracer and therapeutic activities, as a means of confirming whether I clearance and radiation doses for therapy procedures can be predicted by tracer activities. Eleven differentiated thyroid cancer patients were followed after receiving tracer and therapeutic I activity. Whole-body I clearance was estimated using radiation detectors and OLINDA/EXM software was used to calculate radiation doses to rm and wb. Tracer I activity of 86 (±14) MBq and therapeutic activity of 8.04 (±1.18) GBq were administered to patients, thereby producing an average wb I effective half-time and residence time of, respectively, 13.51 (±4.05) and 23.13 (±5.98) h for tracer activities and 13.32 (±3.38) and 19.63 (±4.77) h for therapy. Radiation doses to rm and wb were, respectively, 0.0467 (±0.0208) and 0.0589 (±0.0207) mGy/MBq in tracer studies and 0.0396 (±0.0169) and 0.0500 (±0.0163) mGy/MBq in therapy. Although the differences were not considered statistically significant between averages, those between the values of effective half-times (P=0.906), residence times (P=0.145), and radiation doses to rm (P=0.393) and to wb (P=0.272), from tracer and therapy procedures, large differences of up to 80% in wb I clearance, and up to 50% in radiation doses were observed when patients were analyzed individually, thus impacting on the total amount of I activity calculated to be safe for application in individual therapy. I biokinetics and radiation doses to rm and wb in therapy procedures are well predicted by diagnostic activities when average values of a group of patients are compared. Nonetheless, when patients are analyzed individually, significant differences may be encountered, thus implying that nuclear medicine therapy-planning requires due consideration of changes in individual patient-body status from initial tracer to final therapy procedures to thus provide appropriate adjustments in therapeutic activities.

Insulin and insulin-like growth factor-1 (lGF-1) inhibit repair of potentially lethal radiation damage and chromosome aberrations and later DNA repair kinetics in plateau-phase A549 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jayanth, V.R.; Belfi, C.A.; Swick, A.R.

1995-08-01

Plateau-phase A549 cells exhibit a high capacity for repair of potentially lethal radiation damage (PLD) when allowed to recover in their own spent medium. Addition of either insulin or insulin-like growth factor-1 (IGF-1) to the spent medium 60 to 120 min before irradiation significantly inhibits PLD repair. The 9-h recovery factor (survival with holding/survival without holding)is reduced from 10.8 {plus_minus} 0.7 to 3.4 {plus_minus}0.3 by insulin and to 3.0 {plus_minus} 0.4 by IGF-1. Neither growth factor alters the cell age distribution of the plateau-phase cells, increases the rate of incorporation of 5-bromo-2{prime}-deoxyuridine into DNA, or alters the extent of radiation-inducedmore » mitotic delay in cells subcultured immediately after irradiation. Both insulin and IGF-1 alter the kinetics for rejoining of DNA double-strand breaks (DSBs), slowing the fast component of rejoining significantly. However, these growth factors have no effect on the initial level of DSBs or on the percentage of residual unrejoined breaks at 120 min postirradiation. Both growth factors affect repair of lesions leading to dicentric, but not to acentric, chromosome aberrations significantly. In control cells (treated with phosphate-buffered saline, 90 min prior to irradiation), the half-time for disappearance of dicentrics was 4.1 h (3.4 to 5.1 h), and 47.1 {plus_minus} 3.7% of the residual damage remained at 24 h postirradiation. Insulin and IGF-1 increased the half-time for disappearance of dicentrics to 5.2 h (3.9 to 7.7 h) and 5.7 h (5.5 to 5.9 h), respectively, and increased residual damage to 56.1 {plus_minus}5.9% and 60.8 {plus_minus} 6.0%, respectively. Overall, these data show that insulin and IGF-1 inhibit PLD repair in A54j9 cells by mechanisms which are independent of changes in cell cycle parameters. The data suggest that the growth factors act by inducing changes in chromatin conformation which promote misrepair of radiation-damaged DNA. 49 refs., 5 figs., 4 tabs.« less

Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments.

PubMed

Sowunmi, Akintunde; Akano, Kazeem; Ntadom, Godwin; Ayede, Adejumoke I; Ibironke, Folasade O; Aderoyeje, Temitope; Adewoye, Elsie O; Fatunmbi, Bayo; Oguche, Stephen; Okafor, Henrietta U; Watila, Ismaila; Meremikwu, Martin; Agomo, Philip; Ogala, William; Agomo, Chimere; Folarin, Onikepe A; Gbotosho, Grace O; Happi, Christian T

2017-02-07

Artemisinin-based combination treatments (ACTs) are the first-line treatments of uncomplicated Plasmodium falciparum malaria in many endemic areas but there are few evaluation of their efficacy in anaemic malarious children. Therapeutic efficacy of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine was evaluated in 437 anaemic and 909 non-anaemic malarious children following treatment during a seven-year period (2008-2014). Patterns of temporal changes in haematocrit were classified based on haematocrit values <30% and ≥30%. Kinetics of the disposition of the deficit in haematocrit from 30% following treatment were evaluated using a non-compartment model. PCR-corrected parasitological efficacy 28 days after start of treatment was significantly higher in artesunate-amodiaquine- compared to artemether-lumefantrine-treated children [97% (95%CI: 92.8-100) versus 96.4% (95%CI: 91.3-99.4), P = 0.02], but it was similar in non-anaemic and anaemic children. Fall in haematocrit/1 000 asexual parasites cleared from peripheral blood was significantly greater at lower compared to higher parasitaemias (P < 0.0001), and in non-anaemic compared to anaemic children (P = 0.007). In anaemic children at presentation, mean anaemia recovery time (AnRT) was 15.4 days (95%CI: 13.3-17.4) and it did not change over the years. Declines in haematocrit deficits from 30% were monoexponential with mean estimated half-time of 1.4 days (95%CI: 1.2-1.6). Anaemia half-time (t ½anaemia ) correlated positively with AnRT in the same patients (r = 0.69, P < 0.0001). Bland-Altman analysis of 10 multiples of t ½anaemia and AnRT showed narrow limit of agreement with insignificant bias (P = 0.07) suggesting both can be used interchangeably in the same patients. Artesunate-amodiaquine and artemether-lumefantrine remain efficacious treatments of uncomplicated P. falciparum infections in non-anaemic and anaemic Nigerian children in the last 7 years of adoption as first-line treatments. These ACTs may also conserve haematocrit at high parasitaemias and in anaemic children. Pan African Clinical Trial Registry PACTR201508001188143 , 3 July 2015; PACTR201510001189370 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015.

The 6th Meeting of the Global Alliance to Eliminate Lymphatic Filariasis: A half-time review of lymphatic filariasis elimination and its integration with the control of other neglected tropical diseases

PubMed Central

2010-01-01

The 6th Meeting of the Global Alliance to Eliminate Lymphatic Filariasis (GAELF6) was held 1-3 June, 2010 in Seoul, Korea, with 150 participants from 38 countries. The year 2010 marks the midpoint between the first GAELF meeting, in 2000, and the World Health Organization (WHO) 2020 goal of global elimination of lymphatic filariasis (LF) as a public health problem. The theme of the meeting, "Half-time in LF Elimination: Teaming Up with Neglected Tropical Diseases (NTDs)," reflected significant integration of LF elimination programmes into a comprehensive initiative to control NTDs. Presentations on LF epidemiology, treatment, research, and programmes highlighted both accomplishments and remaining challenges. The WHO strategy to interrupt LF transmission is based on annual mass drug administration (MDA) using two-drug combinations. After mapping the geographic distribution of LF, MDA is implemented for ≥ 5 years, followed by a period of post-MDA surveillance, and, ultimately, verification of LF elimination. Morbidity management further reduces disease burden. Of 81 countries considered LF-endemic in 2000, 52 (64.2%) have begun MDA; 10 (12.3%) others with low-level transmission are unlikely to require MDA. In 2008, ~695 million people were offered treatment (51.7% of the at-risk population); ~496 million participated. Approximately 22 million people have been protected from LF infection and disease, with savings of ~US $24.2 billion. Morbidity management programmes have been implemented in 27 (33.3%) countries. Significant challenges to LF elimination remain. These include: initiating MDA in the remaining 19 countries that require it; achieving full geographic coverage in countries where MDA has started; finding alternative strategies to address the problem of Loa loa co-endemicity in Central Africa; developing strategies to treat urban populations; initiating and sustaining MDA in settings of armed conflict; developing refined guidelines and procedures for stopping MDA, for post-MDA surveillance, and for verifying the elimination of LF; and integrating morbidity management into all LF elimination programmes. Scientific research and enhanced advocacy for NTDs remain critical for addressing these challenges. GAELF6 was characterized by enthusiasm and recognition that "teaming up with NTDs" offers opportunities for new partnerships, fresh perspectives, enhanced advocacy, and greater programmatic integration in a rapidly changing global health environment. PMID:20961435

Rapid desensitization of the rat α7 nAChR is facilitated by the presence of a proline residue in the outer β-sheet

PubMed Central

McCormack, Thomas J; Melis, Claudio; Colón, José; Gay, Elaine A; Mike, Arpad; Karoly, Robert; Lamb, Patricia W; Molteni, Carla; Yakel, Jerrel L

2010-01-01

The rat α7 nicotinic acetylcholine receptor (nAChR) has a proline residue near the middle of the β9 strand. The replacement of this proline residue at position 180 (P180) by either threonine (α7-P180T) or serine (α7-P180S) slowed the onset of desensitization dramatically, with half-times of ∼930 and 700 ms, respectively, compared to 90 ms for the wild-type receptor. To investigate the importance of the hydroxyl group on the position 180 side-chains, the mutant receptors α7-P180Y and α7-P180F were studied and showed half-times of desensitization of 650 and 160 ms, respectively. While a position 180 side-chain OH group may contribute to the slow desensitization rates, α7-P180S and α7-P180V resulted in receptors with similar desensitization rates, suggesting that increased backbone to backbone H bonding expected in the absence of proline at position 180 would likely exert a great effect on desensitization. Single channel recordings indicated that for the α7-P180T receptor there was a significantly reduced closed time without any change in single channel conductance (as compared to wild-type). Kinetic simulations indicated that all changes observed for the mutant channel behaviour were reproduced by decreasing the rate of desensitization, and increasing the microscopic affinity to resting receptors. Molecular dynamics (MD) simulations on a homology model were used to provide insight into likely H bond interactions within the outer β-sheet that occur when the P180 residue is mutated. All mutations analysed increased about twofold the predicted number of H bonds between the residue at position 180 and the backbone of the β10 strand. Moreover, the α7-P180T and α7-P180S mutations also formed some intrastrand H bonds along the β9 strand, although H bonding of the OH groups of the threonine or serine side-chains was predicted to be infrequent. Our results indicate that rapid desensitization of the wild-type rat α7 nAChR is facilitated by the presence of the proline residue within the β9 strand. PMID:20837638

Modeling a 15-min extravehicular activity prebreathe protocol using NASA's exploration atmosphere (56.5 kPa/34% O2)

NASA Astrophysics Data System (ADS)

Abercromby, Andrew F. J.; Conkin, Johnny; Gernhardt, Michael L.

2015-04-01

NASA's plans for future human exploration missions utilize a new atmosphere of 56.5 kPa (8.2 psia), 34% O2, 66% N2 to enable rapid extravehicular activity (EVA) capability with minimal gas losses; however, existing EVA prebreathe protocols to mitigate risk of decompression sickness (DCS) are not applicable to the new exploration atmosphere. We provide preliminary analysis of a 15-min prebreathe protocol and examine the potential benefits of intermittent recompression (IR) and an abbreviated N2 purge on crew time and gas consumables usage. A probabilistic model of decompression stress based on an established biophysical model of DCS risk was developed, providing significant (p<0.0001) prediction and goodness-of-fit with 84 cases of DCS in 668 human altitude exposures including a variety of pressure profiles. DCS risk for a 15-min prebreathe protocol was then estimated under different exploration EVA scenarios. Estimated DCS risk for all EVA scenarios modeled using the 15-min prebreathe protocol ranged between 6.1% and 12.1%. Supersaturation in neurological tissues (5- and 10-min half-time compartments) is prevented and tissue tensions in faster half-time compartments (≤40 min), where the majority of whole-body N2 is located, are reduced to about the levels (30.0 vs. 27.6 kPa) achieved during a standard Shuttle prebreathe protocol. IR reduced estimated DCS risk from 9.7% to 7.9% (1.8% reduction) and from 8.4% to 6.1% (2.3% reduction) for the scenarios modeled; the penalty of N2 reuptake during IR may be outweighed by the benefit of decreased bubble size. Savings of 75% of purge gas and time (0.22 kg gas and 6 min of crew time per person per EVA) are achievable by abbreviating the EVA suit purge to 20% N2 vs. 5% N2 at the expense of an increase in estimated DCS risk from 9.7% to 12.1% (2.4% increase). A 15-min prebreathe protocol appears feasible using the new exploration atmosphere. IR between EVAs may enable reductions in suit purge and prebreathe requirements, decompression stress, and/or suit operating pressures. Ground trial validation is required before operational implementation.

Maximum likelihood analysis of bioassay data from long-term follow-up of two refractory PuO2 inhalation cases.

PubMed

Avtandilashvili, Maia; Brey, Richard; James, Anthony C

2012-07-01

The U.S. Transuranium and Uranium Registries' tissue donors 0202 and 0407 are the two most highly exposed of the 18 registrants who were involved in the 1965 plutonium fire accident at a defense nuclear facility. Material released during the fire was well characterized as "high fired" refractory plutonium dioxide with 0.32-μm mass median diameter. The extensive bioassay data from long-term follow-up of these two cases were used to evaluate the applicability of the Human Respiratory Tract Model presented by International Commission on Radiological Protection in Publication 66 and its revision proposed by Gregoratto et al. in order to account for the observed long-term retention of insoluble material in the lungs. The maximum likelihood method was used to calculate the point estimates of intake and tissue doses and to examine the effect of different lung clearance, blood absorption, and systemic models on the goodness-of-fit and estimated dose values. With appropriate adjustments, Gregoratto et al. particle transport model coupled with the customized blood absorption parameters yielded a credible fit to the bioassay data for both cases and predicted the Case 0202 liver and skeletal activities measured postmortem. PuO2 particles produced by the plutonium fire are extremely insoluble. About 1% of this material is absorbed from the respiratory tract relatively rapidly, at a rate of about 1 to 2 d (half-time about 8 to 16 h). The remainder (99%) is absorbed extremely slowly, at a rate of about 5 × 10(-6) d (half-time about 400 y). When considering this situation, it appears that doses to other body organs are negligible in comparison to those to tissues of the respiratory tract. About 96% of the total committed weighted dose equivalent is contributed by the lungs. Doses absorbed by these workers' lungs were high: 3.2 Gy to AI and 6.5 Gy to LNTH for Case 0202 (18 y post-intake) and 3.2 Gy to AI and 55.5 Gy to LNTH for Case 0407 (43 y post-intake). This evaluation supports the Gregoratto et al. proposed revision to the ICRP 66 model when considering situations of extremely insoluble particles.

Development and intra-institutional and inter-institutional validation of a comprehensive new hepatobiliary software: Part 1--Liver and gallbladder function.

PubMed

Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Gambhir, Sanjiv Sam; Rodrigues, Cesar; Rosenberg, Jarrett; Schiepers, Christiaan; Buxton-Thomas, Muriel

2009-12-01

To develop a software tool for quantification of liver and gallbladder function, and to assess the repeatability and reproducibility of measurements made with it. The software tool developed with the JAVA programming language uses the JAVA2 Standard Edition framework. After manual selection of the regions of interest on a 99mTc hepatic iminodiacetic acid study, the program calculates differential hepatic bile flow, basal duodeno-gastric bile reflux (B-DGBR), hepatic extraction fraction (HEF) of both the lobes with deconvolutional analysis and excretion half-time with nonlinear least squares fit. Gallbladder ejection fraction, ejection period (EP), ejection rate (ER), and postcholecystokinin (CCK) DGBR are calculated after stimulation with CCK-8. To assess intra-observer repeatability and intra-observer reproducibility, measurements from 10 normal participants were analyzed twice by three nuclear medicine technologists at the primary center. To assess inter-site reproducibility, measurements from a superset of 24 normal participants were also assessed once by three observers at the primary center and single observer at three other sites. For the 24 control participants, mean+/-SD of hepatic bile flow into gallbladder was 63.87+/-28.7%, HEF of the right lobe 100+/-0%, left lobe 99.43+2.63%, excretion half-time of the right lobe 21.50+6.98 min, left lobe 28.3+/-11.3 min. Basal DGBR was 1.2+/-1.0%. Gallbladder ejection fraction was 80+/-11%, EP 15.0+/-3.0 min, ER 5.8+/-1.6%/min, and DGBR-CCK 1.3+/-2.3%. Left and right lobe HEF was virtually identical across readers. All measures showed high repeatability except for gallbladder bile flow, basal DGBR, and EP, which exhibited marginal repeatability. Ejection fraction exhibited high reproducibility. There was high concordance among the three primary center observers except for basal DGBR, EP, and ER. Concordance between the primary site and one of the other sites was high, one was fair, and one was poor. New United States Food and Drug Administration-approved personal computer-based Krishnamurthy Hepato-Biliary Software for quantification of the liver and gallbladder function shows promise for consistently repeatable and reproducible results both within and between institutions, and may help to promote universal standardization of data acquisition and analysis in nuclear hepatology.

Rapid desensitization of the rat α7 nAChR is facilitated by the presence of a proline residue in the outer β-sheet.

PubMed

McCormack, Thomas J; Melis, Claudio; Colón, José; Gay, Elaine A; Mike, Arpad; Karoly, Robert; Lamb, Patricia W; Molteni, Carla; Yakel, Jerrel L

2010-11-15

The rat α7 nicotinic acetylcholine receptor (nAChR) has a proline residue near the middle of the β9 strand. The replacement of this proline residue at position 180 (P180) by either threonine (α7-P180T) or serine (α7-P180S) slowed the onset of desensitization dramatically, with half-times of ~930 and 700 ms, respectively, compared to 90 ms for the wild-type receptor. To investigate the importance of the hydroxyl group on the position 180 side-chains, the mutant receptors α7-P180Y and α7-P180F were studied and showed half-times of desensitization of 650 and 160 ms, respectively. While a position 180 side-chain OH group may contribute to the slow desensitization rates, α7-P180S and α7-P180V resulted in receptors with similar desensitization rates, suggesting that increased backbone to backbone H bonding expected in the absence of proline at position 180 would likely exert a great effect on desensitization. Single channel recordings indicated that for the α7-P180T receptor there was a significantly reduced closed time without any change in single channel conductance (as compared to wild-type). Kinetic simulations indicated that all changes observed for the mutant channel behaviour were reproduced by decreasing the rate of desensitization, and increasing the microscopic affinity to resting receptors. Molecular dynamics (MD) simulations on a homology model were used to provide insight into likely H bond interactions within the outer β-sheet that occur when the P180 residue is mutated. All mutations analysed increased about twofold the predicted number of H bonds between the residue at position 180 and the backbone of the β10 strand. Moreover, the α7-P180T and α7-P180S mutations also formed some intrastrand H bonds along the β9 strand, although H bonding of the OH groups of the threonine or serine side-chains was predicted to be infrequent. Our results indicate that rapid desensitization of the wild-type rat α7 nAChR is facilitated by the presence of the proline residue within the β9 strand.

Binding characteristics of levetiracetam to synaptic vesicle protein 2A (SV2A) in human brain and in CHO cells expressing the human recombinant protein.

PubMed

Gillard, Michel; Chatelain, Pierre; Fuks, Bruno

2006-04-24

A specific binding site for the antiepileptic drug levetiracetam (2S-(oxo-1-pyrrolidinyl)butanamide, Keppra) in rat brain, referred to as the levetiracetam binding site, was discovered several years ago. More recently, this binding site has been identified as the synaptic vesicle protein 2A (SV2A), a protein present in synaptic vesicles [Lynch, B., Lambeng, N., Nocka, K., Kensel-Hammes, P., Bajjalieh, S.M., Matagne, A., Fuks, B., 2004. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc. Natl. Acad. Sci. USA, 101, 9861-9866.]. In this study, we characterized the binding properties of levetiracetam in post-mortem human brain and compared them to human SV2A expressed in Chinese hamster ovary (CHO) cells. The results showed that the binding properties of levetiracetam and [3H]ucb 30889, an analogue that was previously characterized as a suitable ligand for levetiracetam binding site/SV2A in rat brain [Gillard, M., Fuks, B., Michel, P., Vertongen, P., Massingham, R. Chatelain, P., 2003. Binding characteristics of [3H]ucb 30889 to levetiracetam binding sites in rat brain. Eur. J. Pharmacol. 478, 1-9.], are almost identical in human brain samples (cerebral cortex, hippocampus and cerebellum) and in CHO cell membranes expressing the human SV2A protein. Moreover, the results are also similar to those previously obtained in rat brain. [3H]ucb 30889 binding in human brain and to SV2A was saturable and reversible. At 4 degrees C, its binding kinetics were best fitted assuming a two-phase model in all tissues. The half-times of association for the fast component ranged between 1 to 2 min and represent 30% to 36% of the sites whereas the half-times for the slow component ranged from 20 to 29 min. In dissociation experiments, the half-times were from 2 to 4 min for the fast component (33% to 49% of the sites) and 20 to 41 min for the slow component. Saturation binding curves led to Kd values for [3H]ucb 30889 of 53+/-7, 55+/-9, 70+/-11 and 75+/-33 nM in human cerebral cortex, hippocampus, cerebellum and CHO cells expressing SV2A respectively. Bmax values around 3-4 pmol/mg protein were calculated in all brain regions. Some of the saturation curves displayed curvilinear Scatchard plots indicating the presence of high and low affinity binding sites. When this was the case, Kd values from 25 to 30 nM for the high affinity sites (24% to 34% of total sites) and from 200 to 275 nM for the low affinity sites were calculated. This was observed in all brain regions and in CHO cell membranes expressing the SV2A protein. It cannot be explained by putative binding of [3H]ucb 30889 to SV2B or C isoforms but may reflect different patterns of SV2A glycosylation or the formation of SV2A oligomers. Competition experiments were performed to determine the affinities for SV2A of a variety of compounds including levetiracetam, some of its analogues and other molecules known to interact with levetiracetam binding sites in rat brain such as bemegride, pentylenetetrazol and chlordiazepoxide. We found an excellent correlation between the affinities of these compounds measured in human brain, rat brain and CHO cells expressing human SV2A. In conclusion, we report for the first time that the binding characteristics of native levetiracetam binding sites/SV2A in human brain and rat brain share very similar properties with human recombinant SV2A expressed in CHO cells.

Lung ventilation studies with technetium-99m Pseudogas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burch, W.M.; Sullivan, P.J.; Lomas, F.E.

1986-06-01

Technetium-99m Pseudogas is an ultrafine near monodisperse aerosol of 0.12-microgram diam particle size. This report describes initial clinical experiences with 27 patients referred for investigation of suspected pulmonary embolism, and in whom Pseudogas ventilation images were compared with a high quality commercial aerosol. An additional group of ten patients with severe COPD was examined in a comparative trial of Pseudogas with 81mKr. Pseudogas was better than a conventional aerosol in reaching a diagnosis of pulmonary embolism using a simple blinded comparison with coded images. In addition, bronchial deposition was minimal unless COPD was severe. Moderately well patients had no difficultymore » inhaling the necessary activity in one or two breaths, and even severely ill and frail aged persons could accomplish the passive breathing maneuver in less than a minute. Clearance of Pseudogas was directly to the systemic circulation with a half-time of 10 min in normal subjects extending up to 100 min in patients with airways disease.« less

Fallout 137Cs in reindeer herders in Arctic Norway.

PubMed

Skuterud, Lavrans; Thørring, Håvard

2015-03-03

Reindeer herders in the Arctic were among the most heavily exposed populations to the global fallout from nuclear weapons testing in the 1950s and 1960s, due to high transfer of radionuclides in the lichens-reindeer-human food chain. Annual studies of (137)Cs in reindeer herders in Kautokeino, Norway, were initiated in 1965 to monitor radiation doses and follow environmental (137)Cs behavior. The (137)Cs concentrations declined from the peak in 1965 with effective half-times of 6-8 years, only interrupted by a temporary doubling in levels from 1986 to 1987 due to the Chernobyl fallout. During the period of 1950-2010 an average herder received an integrated effective dose from incorporated (137)Cs of about 18 mSv. This dose represents an insignificant increase in the risk for developing cancer. Health studies even show a significantly lower cancer incidence among Sámis and reindeer herders in northern Norway compared to other populations in the same area.

Implications of human tissue studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathren, R.L.

1986-10-01

Through radiochemical analysis of voluntary tissue donations, the United States Transuranium and Uranium Registries are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole body contributions to the Transuranium Registry revealed an inverse proportionality between actinide concentration and bone ash fraction. The analysis of a whole body with a documented /sup 241/Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies of the Registries are designed to evaluate in vivo estimates of actinide depositionmore » with those derived from postmortem tissue analysis, compare results of animal experiments with human data, and reviw histopathologic slides for tissue toxicity that might be attributable to exposure to uranium and the transuranic elements. The implications of these recent findings and other work of the Registries are discussed from the standpoint of their potential impact on biokinetic modeling, internal dose assessment, safety standards, and operational health physics practices.« less

Fitting a single-phase model to the post-exercise changes in heart rate and oxygen uptake.

PubMed

Stupnicki, R; Gabryś, T; Szmatlan-Gabryś, U; Tomaszewski, P

2010-01-01

The kinetics of post-exercise heart rate (HR) and oxygen consumption (EPOC) was studied in 10 elite cyclists subjected to four laboratory cycle ergometer maximal exercises lasting 30, 90, 180 or 360 s. Heart rate and oxygen uptake (VO2) were recorded over a period of 6 min after the exercise. By applying the logit transformation to the recorded variables and relating them to the decimal logarithm of the recovery time, uniform single-phase courses of changes were shown for both variables in all subjects and exercises. This enabled computing half-recovery times (t(1/2)) for both variables. Half-time for VO2 negatively correlated with square root of exercise duration (within-subject r = -0.629, p < 0.001), the total post-exercise oxygen uptake till t(1/2) was thus constant irrespectively of exercise intensity. The method is simple and enables reliable comparisons of various modes of exercise with respect to the rate of recovery.

The stark effect on the spectrum energy of tritium in first excited state with relativistic condition

NASA Astrophysics Data System (ADS)

Prastowo, S. H. B.; Supriadi, B.; Bahri, S.; Ridlo, Z. R.

2018-04-01

This research discussed about the correction of Stark Effect on Tritium atoms in the first excited state with relativistic conditions. The approach used to solve this Stark Effect correction was the perturbation theory which was from time independent degenerate perturbation theory to second-order correction. The Stark Effect on the excited state made the spectrum energy polarization of Tritium which was included in the isotope of hydrogen with an electron moving around the nucleus with high velocity. Hence, the relativistic correction affected the spectrum energy shift. Tritium was a radioactive material having half-time 12,3 years and relatively safe. The Tritium application was a material for the manufacture of nuclear battery. The most effective external electric field that should give to Tritium was 108 V/mith the total correction energy that was 0,97398557 × 10-21 Joule. Therefore, its effect reduced the binding energy between electron and nucleus, and increased the power of Tritium Betavoltaics Battery.

Release of Mps1 from kinetochores is crucial for timely anaphase onset.

PubMed

Jelluma, Nannette; Dansen, Tobias B; Sliedrecht, Tale; Kwiatkowski, Nicholas P; Kops, Geert J P L

2010-10-18

Mps1 kinase activity is required for proper chromosome segregation during mitosis through its involvements in microtubule-chromosome attachment error correction and the mitotic checkpoint. Mps1 dynamically exchanges on unattached kinetochores but is largely removed from kinetochores in metaphase. Here we show that Mps1 promotes its own turnover at kinetochores and that removal of Mps1 upon chromosome biorientation is a prerequisite for mitotic checkpoint silencing. Inhibition of Mps1 activity increases its half-time of recovery at unattached kinetochores and causes accumulation of Mps1 protein at these sites. Strikingly, preventing dissociation of active Mps1 from kinetochores delays anaphase onset despite normal chromosome attachment and alignment, and high interkinetochore tension. This delay is marked by continued recruitment of Mad1 and Mad2 to bioriented chromosomes and is attenuated by Mad2 depletion, indicating chronic engagement of the mitotic checkpoint in metaphase. We propose that release of Mps1 from kinetochores is essential for mitotic checkpoint silencing and a fast metaphase-to-anaphase transition.

Tissue Doppler imaging and echo-Doppler findings associated with a mitral valve stenosis with an immobile posterior valve leaflet in a bull terrier.

PubMed

Tidholm, A; Nicolle, A P; Carlos, C; Gouni, V; Caruso, J L; Pouchelon, J L; Chetboul, V

2004-04-01

A mitral valve stenosis was diagnosed in a 2-year-old female Bull Terrier by use of two-dimensional (2-D) and M-mode echocardiography, colour-flow imaging and spectral Doppler examinations. Tissue Doppler Imaging was also performed to assess the segmental radial myocardial motion. The mitral valve stenosis was characterized by a decreased mitral orifice area/left ventricle area ratio (0.14), an increased early diastolic flow velocity (E wave = 1.9 m/s), a prolonged pressure half-time (106 ms) and a decreased E-F slope (4.5 cm/s) on pulsed-wave Doppler examination. This mitral stenosis was associated with an immobile posterior leaflet, as seen on 2-D and M-mode echocardiography. Immobility of the posterior mitral leaflet is considered to be a rare finding in humans and, to our knowledge, has not been precisely documented in dogs with mitral valve stenosis.

Lateral Movement of Water and Sugar Across Xylem in Sugarcane Stalks

PubMed Central

Bull, T. A.; Gayler, K. R.; Glasziou, K. T.

1972-01-01

Laterally connected vascular bundles in the nodes of sugarcane (Saccharum species cv. Pindar) stalks allow a rapid redistribution of water across the stalk should the vascular continuity be partly disrupted. Tritiated water supplied to the roots exchanged rapidly between the xylem and storage tissue so that net movement up the stalk was slow. The half-time for exchange in a labeled stalk was about 4 hours so that the entire water content of a sugarcane stalk can turn over at least once in a single day. No rapid flux of sugar between xylem and phloem or xylem and storage tissue was detected. Functional xylem contained only low sugar concentrations: less than 0.3% w/v in the stalk and less than 0.02% w/v in the leaf. Previous reports of high sugar levels (9% w/v) in sugarcane stalk xylem reflect some degree of xylem blockage followed by a slow equilibration with free space sugars in the storage tissue. PMID:16658067

99mTc-DTPA diuretic renal scintigraphy in dogs with nephroureterolithiasis

PubMed Central

Hecht, Silke; Lawson, S. Meg; Lane, India F.; Sharp, Dorothy E.; Daniel, Gregory B.

2010-01-01

This study evaluated the results of diuretic renal scintigraphy in dogs with urolithiasis. Eighty-three kidneys with nephroureterolithiasis +/− renal pelvis/ureteral dilation were included in the study. Sixty-three kidneys showed a non-obstructive pattern, with a steep drop or gradual downward slope of renal time-activity curve (TAC). Excretion half-time of radiopharmaceutical (T1/2) was 3.99 (2.99 to 7.95) min. Three kidneys showed an obstructive pattern, with continuous rise of the TAC and median T1/2 of −10.71 (−5.20 to −17.56) min. Fifteen kidneys had non-diagnostic studies characterized by flat TAC. Individual kidney glomerular filtration rate was < 0.5 mL/min/kg body weight in most non-diagnostic studies. Diuretic renal scintigraphy appears to be a useful adjunct modality to rule out or confirm ureteral obstruction in dogs. Additional diagnostic procedures may be necessary to achieve a definitive diagnosis in cases of severely impaired renal function. PMID:21358928

Acetazolamide on the ventral medulla of the cat increases phrenic output and delays the ventilatory response to CO2.

PubMed Central

Coates, E L; Li, A H; Nattie, E E

1991-01-01

1. Acetazolamide (0.1 mM) applied to the surface of the rostral ventrolateral medulla or microinjected beneath the medullary surface in chloralose-urethane-anaesthetized, vagotomized, carotid-denervated, paralysed, servo-ventilated cats produced a long-lasting increase in integrated phrenic nerve activity. 2. Extracellular pH measured beneath the rostral ventrolateral medulla exhibited a long-lasting decrease after surface acetazolamide but was not a good predictor, in each individual animal, of changes in phrenic activity. 3. Medullary carbonic anhydrase inhibition reduced the slope and the half-time of the phrenic response to rapid step CO2 increases. Conversely, acetazolamide did not affect the phrenic response to steady-state CO2 increases. 4. These data indicate that localized inhibition of medullary carbonic anhydrase causes a centrally mediated increase in ventilation that we attribute to medullary tissue hypercapnia and acidosis. In addition, these data indicate that medullary carbonic anhydrase may play a role in central CO2 chemotransduction. Images Fig. 8 PMID:1816381

Diffusion of 99-technetium in compacted bentonite under aerobic and anaerobic conditions

NASA Astrophysics Data System (ADS)

Večerník, P.; Jedináková-Křížová, V.

2006-01-01

The main aim of this study was to investigate diffusion of technetium 99Tc under different conditions. Because technetium represents one of the most dangerous fission products due to its very long halftime and high mobility in aerobic conditions diffusion experiments of technetium (as 99TcO 4 - anion) in Czech bentonite from Rokle locality have been carried out. For performance and evaluation of experiments the through-diffusion method was chosen and apparent (Da) and effective (De) diffusion coefficients were evaluated. The effects of particle mesh-size, dry bulk density and aerobic or anaerobic conditions on diffusion were studied. In the presence of oxygen, technetium occurs in oxidation state VII, as an anion, soluble and mobile in the environment. However, under reducing conditions it occurs in a lower oxidation states, mainly as insoluble oxides or hydroxides. Aerobic experiments were carried out under laboratory conditions and anaerobic experiments were performed in a nitrogen atmosphere in a glove box, to simulate the real underground conditions.

Assessment of the Dyeing Properties of the Pigments Produced by Talaromyces spp.

PubMed Central

Oliveira, Jorge; Sousa-Gallagher, Maria; Montañez, Julio Cesar

2017-01-01

The high production yields of pigments by Talaromyces spp. and their high thermal stability have implied that industrial application interests may emerge in the food and textile industries, as they both involve subjecting the colourants to high temperatures. The present study aimed to assess the potential application of the pigments produced by Talaromyces spp. in the textile area by studying their dyeing properties. Dyeing studies were performed on wool. The dyeing process consisted of three stages: scouring, mordanting, and dyeing. Two different mordants (alum, A; ferric chloride, F) were tested at different concentrations on fabric weight (A: 5, 10, 15%; F: 10, 20, 30%). The mordanting process had a significant effect on the final colour of the dyed fabrics obtained. The values of dyeing rate constant (k), half-time of dyeing (t1/2), and sorption kinetics behaviour were evaluated and discussed. The obtained results showed that pigments produced by Talaromyces spp. could serve as a source for the natural dyeing of wool textiles. PMID:29371555

Recovery from TBT pollution in English Channel environments: A problem solved?

PubMed

Langston, W J; Pope, N D; Davey, M; Langston, K M; O' Hara, S C M; Gibbs, P E; Pascoe, P L

2015-06-30

Following recognition of effects in the 1980s, tributyltin (TBT) has been monitored at sites in the English Channel to evaluate the prognosis for biota - spanning the introduction of restrictions on TBT use on small boats and the recent phase-out on the global fleet. We describe how persistence and impact of TBT in clams Scrobicularia plana has changed during this period in Southampton Water and Poole Harbour. TBT contamination (and loss) in water, sediment and clams reflects the abundance and type of vessel activity: half-times in sediment (up to 8y in Poole, 33y in Southampton) are longest near commercial shipping. Recovery of clam populations - slowest in TBT-contaminated deposits - provides a useful biological measure of legislative efficacy in estuaries. On rocky shores, recovery from imposex in Nucella lapillus is evident at many sites but, near ports, is prolonged by shipping impacts, including sediment legacy, for example, in the Fal. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vitro degradation of neurotensin in human plasma.

PubMed

Lee, Y C; Uttenthal, L O; Smith, H A; Bloom, S R

1986-01-01

To study the degradation of neurotensin in plasma in vitro, fresh human plasma was incubated with neurotensin in the presence and absence of the peptidase inhibitors pepstatin A, EDTA, PMSF and aprotinin. The half-time of disappearance of neurotensin at 37 degrees C was calculated to be 226 min in vitro as opposed to 1.4 min in vivo when measured by radioimmunoassay with a C-terminally directed neurotensin antiserum. Both gel filtration and reversed phase high-pressure liquid chromatography (HPLC) showed that the main degradation product of neurotensin in human plasma in vitro was chromatographically and immunologically identical to neurotensin 1-8 and HPLC also demonstrated the formation of neurotensin 1-11. The loss of neurotensin incubated in human plasma in vitro was greatly reduced by EDTA but not by the other peptidase inhibitors tested. In this respect peptidase(s) responsible for the degradation of neurotensin in plasma differ from those present in brain homogenates. EDTA may be of importance in the preservation of neurotensin in plasma samples.

Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glowniak, J.V.; Turner, F.E.; Gray, L.L.

1989-07-01

Iodine-123 metaiodobenzylguanidine ((/sup 123/I)MIBG) is a norepinephrine analog which can be used to image the sympathetic innervation of the heart. In this study, cardiac imaging with (/sup 123/I)MIBG was performed in patients with idiopathic congestive cardiomyopathy and compared to normal controls. Initial uptake, half-time of tracer within the heart, and heart to lung ratios were all significantly reduced in patients compared to normals. Uptake in lungs, liver, salivary glands, and spleen was similar in controls and patients with cardiomyopathy indicating that decreased MIBG uptake was not a generalized abnormality in these patients. Iodine-123 MIBG imaging was also performed in cardiacmore » transplant patients to determine cardiac nonneuronal uptake. Uptake in transplants was less than 10% of normals in the first 2 hr and nearly undetectable after 16 hr. The decreased uptake of MIBG suggests cardiac sympathetic nerve dysfunction while the rapid washout of MIBG from the heart suggests increased cardiac sympathetic nerve activity in idiopathic congestive cardiomyopathy.« less

Human absorption and retention of polonium-210 from caribou meat.

PubMed

Thomas, P A; Fisenne, I; Chorney, D; Baweja, A S; Tracy, B L

2001-01-01

The gastrointestinal (GI) absorption factors and the biological retention times for polonium were determined for a group of 14 volunteers--seven men and seven women--from Saskatoon, Saskatchewan, Canada. Each volunteer consumed 2.0 kg of caribou meat containing known amounts of naturally occurring 210Po. Urine and faecal samples were collected for up to 65 days after meat consumption and analysed for 210Po. The average GI absorption factor for the 14 volunteers was 56 +/- 4% (range = 31-71%), not significantly different from the ICRP value of 50%. About 3% of absorbed polonium underwent prompt excretion by the urinary pathway. The remainder was retained by the body with a half-time >100 days, compared to the ICRP value of 50 days. The effect of these findings increases the dose estimate for ingestion of 210Po in food by a factor of 1.5 to 3.5. Thus, background doses to people consuming caribou and reindeer may be higher than previously thought.

Experimental basis of myocardial imaging with 123I-labeled hexadecenoic acid.

PubMed

Poe, N D; Robinson, G D; Graham, L S; MacDonald, N S

1976-12-01

Progress in myocardial perfusion imaging has been slowed by the lack or radiopharmaceuticals with suitable physical and biologic characteristics. Hexadecenoic acid, terminally labeled with 123I, partially overcomes these limitations by providing a compound that concentrates in the myocardium in proportion to relative regional blood flow and carries a gamma-emitter with desirable detection and imaging qualities. After intravenous injection in experimental animals, the clearance half-times of hexadecenoic acid for blood and myocardium are 1.7 and 20 min, respectively. These values compare favorably with 18-carbon fatty-acid analogs labeled with 11C. In acute and chronic infarction, similar distribution patterns are found for hexadecenoic acid and 43K, which indicates that hexadecenoic acid is a suitable substitute for the potassium analogs now in use for myocardial imaging. Because of the high count rates obtainable with 123I-hexadecenoic acid, good-guality images can be acquired in as little as 2-3 min per view. Iodine-123-hexadecenoic acid is potentially a useful radiopharmaceutical for clinical application.

The biodistribution and toxicity of plutonium, americium and neptunium.

PubMed

Taylor, D M

1989-07-15

In the nuclear fuel cycle the transuranic radionuclides plutonium-239, americium-241 and neptunium-237 would probably present the most serious hazard to human health if released into the environment. Despite differences in their solution chemistry the three elements exhibit remarkable similarity in their biochemical behaviour, apparently sharing similar transport pathways in blood and cells. After entering the blood the elements deposit predominantly in liver and skeleton, where retention appears to be prolonged, with half-times of the order of years. The principal late effects of all three radionuclides are the induction of cancers of bone, lung or liver. For the latter tumours the induction risk per unit radiation dose appears similar for the three radionuclides. But in bone there are indications that, due to microscopic differences in the distribution of the alpha-particle radiation dose, the efficiency of bone cancer induction may increase in the order americium-241 less than plutonium-239 less than neptunium-237. No case of human cancer induced by these radionuclides is known.

Preliminary report on a population that received a heavy exposure to methyl mercury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clarkson, T.W.; Smith, J.C.; Bakir, F.

1973-01-01

An epidemic of methyl mercury poisoning due to the consumption of homemade bread prepared from wheat treated with a methyl mercury fungicide occurred in Iraq in the winter of 1971-1972, with 6530 cases admitted to hospitals. Four hundred and fifty nine died in hosptials. Observations on 16 patients over a period of 60 days indicated a median clearance half-time from blood of approximately 70 days. Concentrations of total mercury in milk averaged 5% of the mercury in simultaneously collected samples of whole blood. Concentrations of total mercury in urine samples did not correlate with concentrations of mercury in blood. Inorganicmore » mercury accounted for the following average percentages of total mercury: 22% in plasma, 40% in milk and 73% in urine. Studies of dose-response relationships indicated that toxic effects of methyl mercury became clinically detectable at body burdens in the range of 0.05-0.8 mg Hg/kg body weight. 8 references, 4 figures.« less

Comparison of oral iodine-131-cellulose and indium-111-DTPA as tracers for colon transit scintigraphy: Analysis by colon activity profiles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smart, R.C.; McLean, R.G.; Gaston-Parry, D.

1991-09-01

In 11 normal subjects and 11 patients with a clinical diagnosis of constipation, oral 131I-cellulose and 111In-DTPA were compared simultaneously as tracers for radionuclide colon transit scintigraphy. Visual assessment of the images revealed no differences between tracers. Quantitation was performed using total and segmental percent retention and the derived value of clearance half-time. In addition, profiles of the activity distribution along the length of the colon were generated and the mean position of the activity in the colon calculated. For all indices, the results were similar in both normal subjects and constipated patients when comparing tracers, although marked differences weremore » present between normal subjects and constipated patients for each tracer. Indium-111-DTPA was easy to administer and dosimetry was more acceptable than for 131I-cellulose, especially in constipated patients. It is concluded that 111In-DTPA is the preferred tracer for oral colon transit scintigraphy.« less

A kinematic model to estimate the effective dose of radioactive isotopes in the human body for radiological protection

NASA Astrophysics Data System (ADS)

Sasaki, S.; Yamada, T.

2013-12-01

The great earthquake attacked the north-east area in Japan in March 11, 2011. The system of electrical facilities to control Fukushima Daiichi nuclear power station was completely destroyed by the following tsunamis. From the damaged reactor containment vessels, an amount of radioactive substances had leaked and been diffused in the vicinity of this station. Radiological internal exposure becomes a serious social issue both in Japan and all over the world. The present study provides an easily understandable, kinematic-based model to estimate the effective dose of radioactive substances in a human body by simplified the complicated mechanism of metabolism. International Commission on Radiological Protection (ICRP) has developed an exact model, which is well-known as a standard method to calculate the effective dose for radiological protection. However, owing to that the above method accord too much with the actual mechanism of metabolism in human bodies, it becomes rather difficult for non-professional people of radiology to gasp the whole images of the movement and the influences of radioactive substances in a human body. Therefore, in the present paper we propose a newly-derived and easily-understandable model to estimate the effective dose. The present method is very similar with the traditional and conventional hydrological tank model. Ingestion flux of radioactive substances corresponds to rain intensity and the storage of radioactive substances to the water storage in a basin in runoff analysis. The key of this method is to estimate the energy radiated from the radioactive nuclear disintegration of an atom by using classical theory of E. Fermi of beta decay and special relativity for various kinds of radioactive atoms. The parameters used in this study are only physical half-time and biological half-time, and there are no intentional and operational parameters of coefficients to adjust our theoretical runoff to observation of ICRP. Figure.1 compares time series of effective cesium-137 dose according to age calculated by ICRP software with calculated by the present method. Plots are calculated values by ICRP, the solid line is analytic solution given from the present method. It should be noted that the present study does not consider complicated mechanism, but it could give equally accurate results comparing to existing research. Time series of effective Cs-137 dose according to age when food contains 1 Bq/year is ingested for 1 year. (Plots are calculated values by ICRP. The solid line is analytic solution given from the present method)

Reticuloendothelial clearance of blood-borne particulates: relevance to experimental lung microembolization and vascular injury.

PubMed

Niehaus, G D; Schumacker, P R; Saba, T M

1980-04-01

The rapid increase in sheep lung vascular permeability observed during Pseudomonas aeruginosa bacteremia may be due to embolization of the pulmonary microvasculature by bloodborne particulates. Since alterations in lung microvascular permeability during mild septicemia in sheep may reflect inefficient RES phagocytic clearance of bacteria as well as products of bacterial induced intravascular coagulation, the opsonic and phagocytic aspects of RES function in sheep (30-50 kg) were compared to other species. RES function was evaluated by both the clearance and relative organ uptake of gelatinized I(131) RE test lipid emulsion and gelatinized colloidal carbon. Immunoreactive opsonic a(2)SB glycoprotein levels were determined by electroimmunoassay. The phagocytic index for RES clearance of the gelatinized (500 mg/kg) test lipid in sheep was 0.019 +/- 0.002 corresponding to a half-time of 16.65 +/- 1.74 minutes. With colloidal carbon (64 mg/kg), the phagocytic index in sheep was 0.080 +/- 0.026, corresponding to a half-time of 6.16 +/- 1.99 minutes. The per cent of injected lipid emulsion (%ID) in major RE organs, on a total organ basis (TO), was: liver = 15.69 +/- 1.65%; spleen = 2.09 +/- 0.78%. Localization in the lung = 31.39 +/- 6.2%. The per cent of carbon localized in major RE organs (%ID/TO) was: liver = 21.37 +/- 1.9%; spleen = 1.95 +/- 0.55%. Localization in the lung = 32.70 +/- 4.55%. In contrast, clearance and organ distribution of the blood-borne test microparticles in rats and dogs at the same relative challenging dose revealed a much more intense and rapid liver and spleen RES uptake with minimal lung localization (1-2%). Immunoreactive opsonic protein concentrations varied greatly with species and directly correlated with efficiency of RES function. Levels observed were: dog = 1285 +/- 135 microg/ml; mouse = 1077 +/- 67 microg/ml; rat = 400 +/- 31 microg/ml; human = 297 +/- 10 microg/ml; and sheep = 184 +/- 13 microg/ml. After intravenous particulate challenge, circulating immunoreactive opsonic protein in the sheep was depleted (p < 0.05) rapidly with partial recovery at 24 hours and mild rebound hyperopsonemia at 48 hours. This pattern is in contrast to the rapid restoration seen in dog and rat within three to six hours postchallenge. Thus, in sheep, the extensive pulmonary localization of blood-borne microparticles appears related to inefficient RES clearance function mediated by a relative deficiency of circulating opsonic protein (plasma fibronectin).

Poorly soluble particulates: searching for a unifying denominator of nanoparticles and fine particles for DNEL estimation.

PubMed

Pauluhn, Jürgen

2011-01-11

Under the new European chemicals regulation, REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) a Derived No-Effect Level (DNEL), i.e., the level of exposure above which humans should not be exposed, is defined. The focus of this paper is to develop a weight-of-evidence-based DNEL-approach for inhaled poorly soluble particles. Despite the common mode of action of inhaled insoluble, spherical particulate matter (PM), a unifying, most appropriate metric conferring pulmonary biopersistence and toxicity has yet not been demonstrated. Nonetheless, there is compelling evidence from repeated rat inhalation exposure studies suggesting that the particle displacement volume is the most prominent unifying denominator linking the pulmonary retained dose with toxicity. Procedures were developed to analyze and model the pulmonary toxicokinetics from short-term to long-term exposure. Six different types of poorly soluble nano- to submicron PMs were compared: ultrafine and pigmentary TiO₂, synthetic iron oxide (Fe₃O₄, magnetite), two aluminum oxyhydroxides (AlOOH, Boehmite) with primary isometric particles approximately of either 10 or 40 nm, and MWCNT. The specific agglomerate densities of these materials ranged from 0.1 g/cm³ (MWCNT) to 5 g/cm³ (Fe₃O₄). Along with all PM, due to their long retention half-times and associated biopersistence in the lung, even short-term inhalation studies may require postexposure periods of at least 3 months to reveal PM-specific dispositional and toxicological characteristics. This analysis provides strong evidence that pulmonary toxicity (sustained inflammation) is dependent on the volume-based cumulative lung exposure dose. Lung toxicity, evidenced by PMN in BAL occurred at lung doses exceeding 10-times the overload threshold. Furthermore, the conclusion is supported that repeated inhalation studies on rats should utilize an experimental window of cumulative volume loads of respirable PM in the range of 1 μl/lung (no-adverse-effect range); however, not exceeding ≈10 μl/lung that would lead to retention half-times increasing 1 year. This can be targeted best by computational toxicology, i.e., the modeling of particle deposition and lung retention biokinetics during the exposure and recovery periods. Inhalation studies exceeding that threshold volume may lead to meaningless findings difficult to extrapolate to any real-life scenario. In summary, this analysis supports a volume-based generic mass concentration of 0.5 μl PM(respirable)/m³ x agglomerate density, independent on nano- or submicron-sized properties, as a generic no-adverse effect level in both rats and humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The primary biodegradation of dispersed crude oil in the sea.

PubMed

Prince, Roger C; McFarlin, Kelly M; Butler, Josh D; Febbo, Eric J; Wang, Frank C Y; Nedwed, Tim J

2013-01-01

Dispersants are important tools for stimulating the biodegradation of large oil spills. They are essentially a bioremediation tool - aiming to stimulate the natural process of aerobic oil biodegradation by dispersing oil into micron-sized droplets that become so dilute in the water column that the natural levels of biologically available nitrogen, phosphorus and oxygen are sufficient for microbial growth. Many studies demonstrate the efficacy of dispersants in getting oil off the water surface. Here we show that biodegradation of dispersed oil is prompt and extensive when oil is present at the ppm levels expected from a successful application of dispersants - more than 80% of the hydrocarbons of lightly weathered Alaska North Slope crude oil were degraded in 60 d at 8 °C in unamended New Jersey (USA) seawater when the oil was present at 2.5 ppm by volume. The apparent halftime of the biodegradation of the hydrocarbons was 13.8 d in the absence of dispersant, and 11 d in the presence of Corexit 9500 - similar to rates extrapolated from the field in the Deepwater Horizon response. Copyright © 2012 Elsevier Ltd. All rights reserved.

Numerical modeling of gravel bed river response to meander straightening: The coupling between the evolution of bed pavement and long profile

NASA Astrophysics Data System (ADS)

Talbot, Tracey; Lapointe, Michel

2002-06-01

Artificial meander straightening (rectification) was conducted in the early 1960s along the Sainte-Marguerite River, Canada, in order to facilitate highway construction along the valley. Previous studies [Talbot and Lapointe, 2002] confirm that vertical reprofiling, coupled with pavement coarsening in the degrading reach, were the main responses counteracting the disequilibrium in gravel transport rates triggered at rectification of this system. Numerical simulations, using SEDROUT2.0, a one-dimensional hydraulic and sediment transport model, and validated against the observed channel response, show the important role played by an advancing wave of pavement coarsening down the rectified reach in modulating the bed degradation response. Simulations extending into the future reveal an asymptotically slowing approach to equilibrium in the middle of the 21st century, with a response half-time of the order of 10 years. In near-threshold gravel bed systems like the Sainte-Marguerite River, pavement coarsening after rectification buffers the system against extreme degradation. Most significantly for watershed management, this also appears to severely limit the extent of propagation of degradation upstream of the rectification.

Solutions for a local equation of anisotropic plant cell growth: an analytical study of expansin activity

PubMed Central

Pietruszka, Mariusz

2011-01-01

This paper presents a generalization of the Lockhart equation for plant cell/organ expansion in the anisotropic case. The intent is to take into account the temporal and spatial variation in the cell wall mechanical properties by considering the wall ‘extensibility’ (Φ), a time- and space-dependent parameter. A dynamic linear differential equation of a second-order tensor is introduced by describing the anisotropic growth process with some key biochemical aspects included. The distortion and expansion of plant cell walls initiated by expansins, a class of proteins known to enhance cell wall ‘extensibility’, is also described. In this approach, expansin proteins are treated as active agents participating in isotropic/anisotropic growth. Two-parameter models and an equation for describing α- and β-expansin proteins are proposed by delineating the extension of isolated wall samples, allowing turgor-driven polymer creep, where expansins weaken the non-covalent binding between wall polysaccharides. We observe that the calculated halftime (t1/2 = εΦ0 log 2) of stress relaxation due to expansin action can be described in mechanical terms. PMID:21227964

(99m)Tc-DTPA diuretic renal scintigraphy in cats with nephroureterolithiasis.

PubMed

Hecht, Silke; Lawson, Sarah M; Lane, India F; Sharp, Dorothy E; Daniel, Gregory B

2010-06-01

The purpose of this study was to evaluate results of diuretic renal scintigraphy in 32 feline kidneys with nephroureterolithiasis and variable degrees of renal pelvis/ureteral dilation. Six kidneys showed a non-obstructive scintigraphic pattern, with a downward slope of time-activity curves (TAC) and a median excretion half-time of radiopharmaceutical (T((1/2))) of 6.09 (5.08-8.43) min. Eight kidneys showed an obstructive pattern, with a continuous rise of TAC and median T((1/2)) of -7.91 (-43.13-0.00) min. In one kidney with presumptive partial obstruction scintigraphic results were equivocal. Seventeen kidneys, most of which had an individual kidney glomerular filtration rate below 0.5ml/min/kg, had non-diagnostic studies. Diuretic renal scintigraphy may be a useful adjunct modality in the diagnosis of ureteral obstruction in some cats if renal function is maintained. However, the large number of non-diagnostic studies in animals with decreased renal function represents a clear limitation of the technique. Copyright 2009 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Lung-clearance classification of radionuclides in calcined phosphate rock dust

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalkwarf, D.R.; Jackson, P.O.

1984-08-01

Lung-clearance classifications for /sup 210/Pb and /sup 210/Po in airborne dust from elemental phosphorus plants were estimated for use with the lung clearance model proposed by the ICRP Task Group on Lung Dynamics. Estimates were based on measurements of dissolution rates for these radionuclides from sized dust samples into simulated lung fluid at 37/sup 0/C. The estimates were expressed in the classification terms of the model, i.e., D, W and Y, indicating lung clearance half-times of 0 to 10 days, 11 to 100 days and more than 100 days. Dust samples were obtained from two plants in the western Unitedmore » States, and dissolution trials were conducted on fractions containing particles with aerodynamic equivalent diameters (AED) of 0 to 3 ..mu..m and of 3 to 10 ..mu..m. The /sup 210/Pb and /sup 210/Po in each of these fractions were classified 100% Class Y. The specific activities of both radionuclides increased with decreasing AED of the particles. 11 references, 1 figure, 4 tables.« less

[Successful management of neurosurgical procedures with continuous infusion of recombinant factor IX in a child with hemophilia B].

PubMed

Yamamoto, Mariko; Nakadate, Hisaya; Iguchi, Umefumi; Masuda, Hiroshi; Sakai, Hirokazu; Ishiguro, Akira

2013-03-01

This report describes the successful management of neurosurgical procedures with continuous infusion of recombinant factor IX (rFIX). A 1-year-old boy with severe hemophilia B was administered prophylactic therapy with rFIX after intracranial bleeding. We found the enlargement of an arachnoid cyst in a follow-up CT scan. He underwent marsupialization of the cyst under the continuous infusion of rFIX. FIX levels were examined in our hospital and the rFIX infusion rate was adjusted in an attempt to keep FIX levels above 90% intraoperatively, and 70% until his 7th post-operative day. We studied the pharmacokinetic profile of rFIX and found a half-time of 25 hours and mean in vivo recovery of 0.69 IU/dl/IU/kg. Reconstituted rFIX also retained at least 95% activity after 72 hours at room temperature. This is the first report of the perioperative management of a child undergoing a neurosurgical procedure under the continuous infusion of rFIX in Japan. Further studies are required before the routine use of this product for continuous infusion.

Assimilation and biological turnover of cesium-134, iodine-131, and chromium-51 in brown crickets, Acheta domesticus (L. )

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Hook, R.I. Jr.; Crossley, D.A. Jr.

1969-01-01

Understanding of radionuclide accumulation by insects requires careful assessment of assimilation and turnover rates. In separate experiments, three radionuclides (/sup 134/Cs, /sup 131/I or /sup 51/Cr) were fed to adult brown crickets for a 24-hr period. The insects were then transferred to nonradioactive food and their whole-body retention measured at 1-hr intervals. The retention of each radionuclide can be described by a sum of two exponential functions, a shorter one related to loss of unassimilated radionuclide from the gut and a longer one describing excretion of assimilated radionuclide from tissues. The shorter components had similar rates (half-time = about 4more » hr) for all three radionuclides, indicating that they were a measure of gut clearance time. Chromium had the lowest assimilation (6%) and cesium the highest (65%). Assimilated /sup 134/Cs and /sup 51/Cr were eliminated at moderate rates (biological half-lives of 62 and 83 hr, respectively) but assimilated /sup 131/I was stored rather than excreted. 18 references, 2 figures, 1 table.« less

Contraction of guinea-pig lung parenchymal strips by substance P and related peptides.

PubMed

Foreman, J C; Shelly, R; Webber, S E

1985-12-01

A dose-response relationship for substance P and contraction of the lung parenchyma strip of the guinea-pig could only be obtained in the presence of a mixture of bacitracin, 1,4 dithio-L-threitol and ethylenediamine tetracetic acid, all at 100 microM, or in the presence of captopril, 1.8 mM. Substance P (50 nM) caused no contraction by itself but produced a shift to the left of the dose-response curve for histamine with a mean dose-ratio of 1.4 +/- 0.2 (S.E. of mean). The peptides physalaemin, eledoisin and kassinin were all approximately equipotent with substance P on the lung strip, in the presence of peptides inhibitors. [D-Pro4, D-Trp7,9,10]-SP4-11, produced dose-related inhibition of the contraction induced by substance P. Substance P activity in guinea-pig lung declined exponentially with a half-time of 2.3 min: bacitracin, dithiothreitol and EDTA (all 100 microM) increased this to 7.2 min and captopril (1.8 mM) to 5.1 min.

Kinetics of anti-carcinoembryonic antigen antibody internalization: effects of affinity, bivalency, and stability

PubMed Central

Schmidt, Michael M.; Thurber, Greg M.

2010-01-01

Theoretical analyses suggest that the cellular internalization and catabolism of bound antibodies contribute significantly to poor penetration into tumors. Here we quantitatively assess the internalization of antibodies and antibody fragments against the commonly targeted antigen carcinoembryonic antigen (CEA). Although CEA is often referred to as a non-internalizing or shed antigen, anti-CEA antibodies and antibody fragments are shown to be slowly endocytosed by LS174T cells with a half-time of 10–16 h, a time scale consistent with the metabolic turnover rate of CEA in the absence of antibody. Anti-CEA single chain variable fragments (scFvs) with significant differences in affinity, stability against protease digestion, and valency exhibit similar uptake rates of bound antibody. In contrast, one anti-CEA IgG exhibits unique binding and trafficking properties with twice as many molecules bound per cell at saturation and significantly faster cellular internalization after binding. The internalization rates measured herein can be used in simple computational models to predict the microdistribution of these antibodies in tumor spheroids. PMID:18408925

1,2,3,4-bis(p-methylbenzylidene sorbitol) accelerates crystallization and improves hole mobility of poly(3-hexylthiophene)

NASA Astrophysics Data System (ADS)

Yuan, Nana; Huo, Hong

2016-02-01

The addition of 1,2,3,4-bis(p-methylbenzylidene sorbitol) (MDBS) does not change the nucleation mechanism or the crystal form of poly(3-hexylthiophene) (P3HT), but its presence increases the crystallization temperature (T c) of P3HT, decreases the crystallization half-time (t 1/2) and accelerates P3HT crystallization, which indicates that MDBS is an effective nucleating agent for P3HT. An acceleration of P3HT crystallization by the addition of MDBS decreases the crystalline size and crystallinity of P3HT, and enhances the connectivity between ordered regions of P3HT, leading to the hole mobility rising from 1.99 × 10-6 to 7.57 × 10-5 cm2 V-1s-1 in P3HT:PCBM blend based hole-only devices with sandwich configurations. Our results suggest that accelerating P3HT crystallization by adding a nucleating agent might be an important factor to improve the hole mobility and balance the electron and hole mobility in a photovoltaic blend.

Acquired tricuspid valve stenosis due to intentionally redundant transvenous lead placement for VDD pacing in two small dogs.

PubMed

Gunther-Harrington, Catherine T; Michel, Adam O; Stern, Joshua A

2015-12-01

Placement of an endocardial VDD pacing lead in small dogs (<12 kg) may necessitate a redundant lead remaining looped in the right atrium for appropriate sensing and pacing. This report documented acquired tricuspid valve stenosis in two small dogs between 8 months and 4 years after VDD pacemaker placement for third-degree atrioventricular block. Echocardiography and Doppler echocardiography identified elevated transtricuspid flow velocities, prolonged pressure half-times, decreased valve leaflet excursions, and tricuspid regurgitation in both cases. Both cases were euthanized secondary to this pacing complication. Necropsy was performed in one case and confirmed adherence between the redundant lead loop, atrial and valve tissue. While VDD pacing in dogs has proven hemodynamic benefits, these benefits have not been demonstrated in terms of survival benefit or clinical signs. The requirement of redundant lead placement in small dogs for appropriate VDD lead function creates potential deleterious effects that should be weighed against the possible clinical value of VDD pacing in these patients. Copyright © 2015 Elsevier B.V. All rights reserved.

From then to now. Too gentle, too polite, too careful?

PubMed

Williams, S

1996-10-01

Oxfam's Gender and Development Unit (GADU) began in 1985 without scheduled time (all personnel had full-time jobs), premises (whatever space was vacant at the time), or money. David Bryer, incoming overseas director, supported the group and gave it an office and a half-time post. GADU's goal was to raise awareness about gender issues within Oxfam, and to formulate policy for the Overseas Division. What was promoted overseas was to be promoted within Oxfam. GADU cooperated with the Oxfam Women's Group, the Equal Opportunities Working Group, and the Creche Committee (which got the workplace nursery started). Members of GADU steering group included persons from education, campaigns, and all area desks. Members would bring gender issues to the attention of their departments, and GADU would meet regularly to discuss strategies and problems. Colleagues remained surprisingly resistant to ideas current in the development world and suspicious of GADU. Although gender is now on Oxfam's agenda, the struggle continues. Perhaps GADU was born too gently; perhaps "the cotton-wool of Oxfam liberalism" should have been ripped off, and "armed struggle" begun.

Droplet-based microfluidics platform for measurement of rapid erythrocyte water transport

PubMed Central

Jin, Byung-Ju; Esteva-Font, Cristina; Verkman, A.S.

2015-01-01

Cell membrane water permeability is an important determinant of epithelial fluid secretion, tissue swelling, angiogenesis, tumor spread and other biological processes. Cellular water channels, the aquaporins, are important drug targets. Water permeability is generally measured from the kinetics of cell volume change in response to an osmotic gradient. Here, we developed a microfluidics platform in which cells expressing a cytoplasmic, volume-sensing fluorescent dye are rapidly subjected to an osmotic gradient by solution mixing inside a ~ 0.1 nL droplet surrounded by oil. Solution mixing time was < 10 ms. Osmotic water permeability was deduced from a single, time-integrated fluorescence image of an observation area in which time after mixing is determined by spatial position. Water permeability was accurately measured in aquaporin-expressing erythrocytes with half-times for osmotic equilibration down to < 50 ms. Compared with conventional water permeability measurements using costly stopped-flow instrumentation, the microfluidics platform here utilizes sub-microliter blood sample volume, does not suffer from mixing artifact, and replaces challenging kinetic measurements by a single image capture using a standard laboratory fluorescence microscope. PMID:26159099

Which method should be the reference method to evaluate the severity of rheumatic mitral stenosis? Gorlin's method versus 3D-echo.

PubMed

Pérez de Isla, Leopoldo; Casanova, Carlos; Almería, Carlos; Rodrigo, José Luis; Cordeiro, Pedro; Mataix, Luis; Aubele, Ada Lia; Lang, Roberto; Zamorano, José Luis

2007-12-01

Several studies have shown a wide variability among different methods to determine the valve area in patients with rheumatic mitral stenosis. Our aim was to evaluate if 3D-echo planimetry is more accurate than the Gorlin method to measure the valve area. Twenty-six patients with mitral stenosis underwent 2D and 3D-echo echocardiographic examinations and catheterization. Valve area was estimated by different methods. A median value of the mitral valve area, obtained from the measurements of three classical non-invasive methods (2D planimetry, pressure half-time and PISA method), was used as the reference method and it was compared with 3D-echo planimetry and Gorlin's method. Our results showed that the accuracy of 3D-echo planimetry is superior to the accuracy of the Gorlin method for the assessment of mitral valve area. We should keep in mind the fact that 3D-echo planimetry may be a better reference method than the Gorlin method to assess the severity of rheumatic mitral stenosis.

Immobilization of endo-polygalacturonase from Aspergillus niger on various types of macromolecular supports.

PubMed

Pifferi, P G; Tramontini, M; Malacarne, A

1989-04-20

Endo-polygalacturonase (endo-PG) was immobilized on a wide range of natural and synthetic macromolecular supports and their modified derivatives representing many chemical classes, including esters, amides, phenols, alkyl- and arylamines, and carboxyl derivatives. The immobilization entailed methods of adsorption alone as well as covalent bond formation using glutaraldehyde or carbodiimide or via the diazo-coupling reaction. The most promising system proved to be immobilization on trimalehylchitosan (TMC) via adsorption followed by treatment with glutaraldehyde (GA). The binding capacity of the support is on the order of 13,000 IU/g, half of which is active. Various properties of immobilized endo-PG were evaluated. The optimum pH of the enzyme shifted to the alkaline side. The relative catalytic activity was considerably high even at room temperature and remained so above 70 degrees C. The thermal stability at pH 3-4 was notably improved by immobilization, the half-time doubling. Finally, the apparent K(m) was greater for immobilized endo-PG than for native enzyme, while the V(max) was smaller for the immobilized enzyme.

Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials.

PubMed

Sowunmi, Akintunde; Fatunmbi, Bayo; Akano, Kazeem; Wewe, Olubunmi A; Agomo, Chimere; Finomo, Finomo; Ebenebe, Joy; Jiya, Nma; Ambe, Jose; Wammanda, Robinson; Ntadom, Godwin; Mokuolu, Olugbenga; Emechebe, George; Ezeigwe, Nnenna; Ayede, Adejumoke I; Adewoye, Elsie O; Gbotosho, Grace O; Folarin, Onikepe A; Happi, Christian T; Oguche, Stephen; Oyibo, Wellington A; Useh, Francis

2017-12-19

Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children. Malarious <5 year-olds randomized to artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine treatments were followed up clinically for 6 weeks. Anaemia was defined as haematocrit <30%; Malaria-attributable fall in haematocrit (MAFH) as the difference between haematocrit 28-42 days post- and pre-treatment; Total MAFH (TMAFH) as the difference between days 28-42 haematocrit and the lowest haematocrit recorded in the first week post-treatment initiation; Drug-attributable fall in haematocrit (DAFH) as the difference between MAFH and TMAFH; Early appearing anaemia (EAA) as haematocrit <30% occurring within 1 week in children with normal haematocrit pre-treatment. Predictors of anaemia pre-treatment, EAA, MAFH or DAFH >4% were evaluated by stepwise multiple logistic regression models. Survival analysis and kinetics of DAFH were evaluated by Kaplan-Meier estimator and non-compartment model, respectively. Pre-treatment, 355 of 959 children were anaemic. Duration of illness >2 days and parasitaemia ≤10,000 μL -1 were independent predictors of anaemia pre-treatment. EAA occurred in 301 of 604 children. Predictors of EAA were age ≤ 15 months, history of fever pre-treatment and enrolment haematocrit ≤35%. The probabilities of progression from normal haematocrit to EAA were similar for all treatments. MAFH >4% occurred in 446 of 694 children; its predictors were anaemia pre-treatment, enrolment parasitaemia ≤50,000 μL -1 , parasitaemia one day post-treatment initiation and gametocytaemia. DAFH >4% occurred in 334 of 719 children; its predictors were history of fever pre-and fever 1 day post-treatment initiation, haematocrit ≥37%, and parasitaemia >100,000 μL -1 . In 432 children, declines in DAFH deficits were monoexponential with overall estimated half-time of 2.2d (95% CI 1.9-2.6). Area under curve of deficits in DAFH versus time and estimated half-time were significantly higher in non-anaemic children indicating greater loss of haematocrit in these children. After ten years of adoption of ACTs, anaemia is common pre-and early post-treatment, falls in haematocrit attributable to a single infection is high, and DAFH >4% is common and significantly lower in anaemic compared to non-anaemic Nigerian children. Pan African Clinical Trial Registry (PACTR) [ PACTR201709002064150, 1 March 2017 ].

Kootenai River Focus Watershed Coordination, 2004-2005 Annual Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kootenai River Network,

2005-07-01

The Kootenai River Network (KRN) was contracted by the Bonneville Power Administration; PPA Project Number 96087200 for the period June 1, 2004 to May 31, 2005 to provide Kootenai River basin watershed coordination services. The prime focus of the KRN Watershed Coordination Program is coordinating projects and disseminating information related to watershed improvement and education and outreach with other interest groups in the Kootenai River basin. The KRN willingly shares its resources with these groups. The 2004-2005 BPA contract extended the original Montana Fish, Wildlife and Parks contract, which was transferred to the Kootenai River Network through a Memorandum ofmore » Understanding in November 2001. The KRN objectives of this contract were carried out by one half-time Watershed Coordinator position in Montana-Idaho (Nancy Zapotocki) and one half-time Watershed Coordination team in British Columbia (Laura and Jim Duncan). Nancy Zapotocki was hired as the KRN US Watershed Coordinator in July 2004. Her extensive work experience in outreach and education and watershed planning complements the Duncans in British Columbia. To continue rejuvenating and revitalizing the KRN, the Board conducted a second retreat in November 2004. The first retreat took place in November 2003. Board and staff members combined efforts to define KRN goals and ways of achieving them. An Education and Outreach Plan formulated by the Watershed Coordinators was used to guide much of the discussions. The conclusions reached during the retreat specified four ''flagship'' projects for 2005-2006, to: (1) Provide leadership and facilitation, and build on current work related to the TMDL plans and planning efforts on the United States side of the border. (2) Continue facilitating trans-boundary British Columbia projects building on established work and applying the KRN model of project facilitation to other areas of the Kootenai basin. (3) Finalize and implement the KRN Education and Outreach plan. (4) Use GIS mapping to prioritize US and BC projects and prioritize education and outreach efforts. The KRN established Kootenay River Network-BC as a registered Society and are pursuing charitable status for this sister organization. Having an organization in both the US and Canada will allow the KRN to apply for and to manage funds as well as to coordinate education and outreach workshops, seminars and tours with greater ease. The recent accomplishments by the Joseph Creek Community Action Team in Cranbrook demonstrate the significant trans-boundary abilities of the KRN. On May 26, 2005, KRN received a prestigious Watershed Stewardship award from the Montana Watershed Coordination Council, which represents over 80 watershed groups in the State of Montana. The award was presented by Governor Brian Schweitzer in the rotunda of the State Capital building in Helena Montana.« less

Therapeutic efficacy and effects of artesunate-amodiaquine and artemether-lumefantrine on malaria-associated anaemia in Nigerian children aged two years and under.

PubMed

Sowunmi, Akintunde; Akano, Kazeem; Ayede, Adejumoke I; Ntadom, Godwin; Adewoye, Elsie O; Fatunmbi, Bayo; Aderoyeje, Temitope

2016-07-06

Artemisinin-based combination therapies are recommended as first-line treatments for uncomplicated falciparum malaria, but there is little evaluation of their efficacy and effects on uncomplicated malaria-associated anaemia in children aged 2 years and under. Parasitological efficacy and effects on malaria-associated anaemia were evaluated in 250 malarious children aged 2 years and under, and efficacy was evaluated in 603 malarious children older than two but younger than 5 years of age following treatment with artesunate-amodiaquine (AA) or artemether-lumefantrine (AL). Kinetics of the disposition of parasitaemia following treatment were evaluated using a non-compartment model. Late-appearing anaemia (LAA) was diagnosed using the following criteria: clearance of parasitaemia, fever and other symptoms occurring within 7 days of starting treatment, adequate clinical and parasitological response on days 28-42, haematocrit (HCT) ≥ 30 % at 1 and/or 2 weeks, a fall in HCT to < 30 % occurring at 3-6 weeks, absence of concomitant illness at 1-6 weeks, and absence of asexual parasitaemia detected using both microscopy and polymerase chain reaction (PCR) at 1-6 weeks. Overall, in children aged 2 years and under, the PCR-corrected parasitological efficacy was 97.2 % (95 % CI 92.8-101.6), which was similar for both treatments. In children older than 2 years, parasitological efficacy was also similar for both treatments, but parasite prevalence 1 day after treatment began was significantly higher, and fever and parasite clearance times were significantly faster in the AA-treated children compared with the AL-treated children. Declines in parasitaemia were monoexponential with an estimated elimination half-time of 1 h. Elimination half-times were similar for both treatments. In children aged 2 years and under who were anaemic at presentation, the mean anaemia recovery time was 12.1 days (95 % CI 10.6-13.6, n = 127), which was similar for both treatments. Relatively asymptomatic LAA occurred in 11 children (4.4 %) aged 2 years and under, the recovery from which was uneventful. This study showed that AA and AL are efficacious treatments for uncomplicated falciparum malaria in Nigerian children aged 2 years and under, and that AA clears parasitaemia and fever significantly faster than AL in children older than 2 years. Both treatments may cause a relatively asymptomatic LAA with uneventful recovery in a small proportion of children aged 2 years and under. Pan African Clinical Trial Registry PACTR201508001188143, 3 July 2015; PACTR201510001189370, 3 July 2015; PACTR201508001191898, 7 July 2015 and PACTR201508001193368, 8 July 2015  http://www.pactr.org .

Kinetic energy definition in velocity Verlet integration for accurate pressure evaluation

NASA Astrophysics Data System (ADS)

Jung, Jaewoon; Kobayashi, Chigusa; Sugita, Yuji

2018-04-01

In molecular dynamics (MD) simulations, a proper definition of kinetic energy is essential for controlling pressure as well as temperature in the isothermal-isobaric condition. The virial theorem provides an equation that connects the average kinetic energy with the product of particle coordinate and force. In this paper, we show that the theorem is satisfied in MD simulations with a larger time step and holonomic constraints of bonds, only when a proper definition of kinetic energy is used. We provide a novel definition of kinetic energy, which is calculated from velocities at the half-time steps (t - Δt/2 and t + Δt/2) in the velocity Verlet integration method. MD simulations of a 1,2-dispalmitoyl-sn-phosphatidylcholine (DPPC) lipid bilayer and a water box using the kinetic energy definition could reproduce the physical properties in the isothermal-isobaric condition properly. We also develop a multiple time step (MTS) integration scheme with the kinetic energy definition. MD simulations with the MTS integration for the DPPC and water box systems provided the same quantities as the velocity Verlet integration method, even when the thermostat and barostat are updated less frequently.

Family violence and football: the effect of unexpected emotional cues on violent behavior.

PubMed

Card, David; Dahl, Gordon B

2011-01-01

We study the link between family violence and the emotional cues associated with wins and losses by professional football teams. We hypothesize that the risk of violence is affected by the “gain-loss” utility of game outcomes around a rationally expected reference point. Our empirical analysis uses police reports of violent incidents on Sundays during the professional football season. Controlling for the pregame point spread and the size of the local viewing audience, we find that upset losses (defeats when the home team was predicted to win by four or more points) lead to a 10% increase in the rate of at-home violence by men against their wives and girlfriends. In contrast, losses when the game was expected to be close have small and insignificant effects. Upset wins (victories when the home team was predicted to lose) also have little impact on violence, consistent with asymmetry in the gain-loss utility function. The rise in violence after an upset loss is concentrated in a narrow time window near the end of the game and is larger for more important games. We find no evidence for reference point updating based on the halftime score.

Family Violence and Football: The Effect of Unexpected Emotional Cues on Violent Behavior*

PubMed Central

Card, David; Dahl, Gordon B.

2013-01-01

We study the link between family violence and the emotional cues associated with wins and losses by local professional football teams. We hypothesize that the risk of violence is affected by the ‘gain-loss’ utility of game outcomes around a rationally expected reference point. Our empirical analysis uses police reports of violent incidents on Sundays during the professional football season. Controlling for the pre-game point spread and the size of the local viewing audience, we find that upset losses (defeats when the home team was predicted to win by 4 or more points) lead to a 10 percent increase in the rate of at-home violence by men against their wives and girlfriends. In contrast, losses when the game was expected to be close have small and insignificant effects. Upset wins (when the home team was predicted to lose) also have little impact on violence, consistent with asymmetry in the gain-loss utility function. The rise in violence after an upset loss is concentrated in a narrow time window near the end of the game, and is larger for more important games. We find no evidence for reference point updating based on the halftime score. PMID:21853617

Distribution and migration of ⁹⁰Sr in components of the Dnieper River basin and the Black Sea ecosystems after the Chernobyl NPP accident.

PubMed

Mirzoyeva, N Yu; Egorov, V N; Polikarpov, G G

2013-11-01

The change in (90)Sr concentrations in hydrobionts, water and bottom sediments of the Chernobyl NPP pond-cooler, the Kievskoe and Kakhovskoe reservoirs, the Northern-Crimean canal and the Black Sea after the Chernobyl NPP accident was studied. The environmental half-times for the decrease of (90)Sr concentrations were determined: in water - 4.1-24.3 years; algae and flowering water plants - 3.6-7.7 years, in molluscs - 2.4-6.7 years, and in fish - 7.8-12.9 years. The time for (90)Sr concentrations to decrease to pre-accident levels were estimated: in freshwater reservoirs and the northwest part of the Black Sea this was 32-44 years, and in freshwater hydrobionts this was 25-73 years. The contribution of dose from (90)Sr to the hydrobionts, sampled from the Kakhovskoe reservoir, the Northern-Crimean canal and the Black Sea, has not reached values which could impact them during the entire post-accident period. This complex of comparative studies was carried out for the first time. Copyright © 2013 Elsevier Ltd. All rights reserved.

Recycling of poly (lactic acid)/silk based bionanocomposites films and its influence on thermal stability, crystallization kinetics, solution and melt rheology.

PubMed

Tesfaye, Melakuu; Patwa, Rahul; Gupta, Arvind; Kashyap, Manash Jyoti; Katiyar, Vimal

2017-08-01

In this study, the effect of silk nanocrystals (SNCs) on the thermal and rheological properties of poly (lactic acid) (PLA) under repetitive extrusion process is investigated. The presence of SNCs facilitates the crystallization process and delaying the thermal degradation of PLA matrix. This leads to the reduction in cold crystallization peak temperature with lower crystallization half-time and higher growth rate. The substantial improvement in nucleation density observed through Polarized Optical Microscope (POM) proves the nucleating effect of SNC in all processing cycles. Moreover, the rheological investigation (complex viscosity, storage and loss modules values) revealed the stabilizing effect of SNC and the drastic degradation of neat PLA (NPLA) in third and fourth cycle is observed to be fortified by the presence of SNC. Cole-Cole plot and cross over frequencies have been correlated with the molar mass distribution of PLA and PLA-Silk composite during processing, which is further supported by the intrinsic viscosity measurement and acid value analysis. This investigation suggests that the melt viscosity and thermal properties of PLA can be stabilized by addition of silk nanocrystals. Copyright © 2017 Elsevier B.V. All rights reserved.

Echocardiographic features of the normofunctional Labcor-Santiago pericardial bioprosthesis.

PubMed

Gonzalez-Juanatey, J R; Garcia-Bengoechea, J B; Vega, M; Rubio, J; Sierra, J; Duran, D; Amaro, A; Gil, M

1994-09-01

Echocardiography was performed in 94 patients with a total of 99 normally functioning Labcor-Santiago bioprostheses, 62 in the aortic and 37 in the mitral position. The following variables were measured: peak and mean transvalvular velocities, peak and mean instantaneous pressure gradients as calculated from the modified Bernoulli equation, pressure half-time, cardiac index, stroke volume and effective orifice area (using continuity and Hatle equations). Regurgitation patterns were sought by transthoracic echocardiography (all valves) and, for selected mitral bioprostheses, by transesophageal echocardiography. Calculated mean aortic pressure gradient ranged from six to 10 mmHg and calculated effective aortic orifice area increased with ring diameter, with means of 1.27 cm2 for the 19 mm valve and 2.58 cm2 for the 27 mm valve. For mitral bioprostheses, mean pressure gradient ranged from 3.0 to 4.5 mmHg and calculated effective orifice area from 2.27 to 2.73 cm2. Only central regurgitation was observed. The Labcor-Santiago pericardial bioprostheses created little resistance to forward flow. In the small aortic root their hemodynamic performance was as good or better than that of other currently available devices. It is hoped that this new design will contribute increased in vivo mechanical durability.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carbaugh, Eugene H.; Lynch, Timothy P.; Cannon, Curt

Three workers incurred inhalation exposures to 241Am oxide as a result of waste sorting and compaction activities. The magnitudes of the exposures were not fully recognized until the following day when an in vivo chest count identified a significant lung deposition of 241Am in a male worker, and DTPA chelation therapy was initiated. Two additional workers (one female and one male) were then identified as sufficiently exposed to also warrant therapy. In vivo bioassay measurements were performed over the ensuing 6 months to quantify the 241Am activity in the lungs, liver, and skeleton. Urine and fecal samples were collected andmore » showed readily detectable 241Am. Clinical lab tests and medical evaluations all showed normal results. There were no significant adverse clinical health effects from the therapy. The estimated 241Am inhalation intakes for the three workers were 1800 Bq, 630 Bq, and 150 Bq. Lung retention showed somewhat longer pulmonary clearance half-times than standard inhalation class W or absorption Type M assumptions. The three underwent slightly different therapy regimes, with therapy effectiveness factors (defined as the ratio of the reference doses without therapy relative to the final assessed doses) of 4.65, 1.93, and 1.67, respectively.« less

A Probability Model of Decompression Sickness at 4.3 Psia after Exercise Prebreathe

NASA Technical Reports Server (NTRS)

Conkin, Johnny; Gernhardt, Michael L.; Powell, Michael R.; Pollock, Neal

2004-01-01

Exercise PB can reduce the risk of decompression sickness on ascent to 4.3 psia when performed at the proper intensity and duration. Data are from seven tests. PB times ranged from 90 to 150 min. High intensity, short duration dual-cycle ergometry was done during the PB. This was done alone, or combined with intermittent low intensity exercise or periods of rest for the remaining PB. Nonambulating men and women performed light exercise from a semi-recumbent position at 4.3 psia for four hrs. The Research Model with age tested the probability that DCS increases with advancing age. The NASA Model with gender hypothesized that the probability of DCS increases if gender is female. Accounting for exercise and rest during PB with a variable half-time compartment for computed tissue N2 pressure advances our probability modeling of hypobaric DCS. Both models show that a small increase in exercise intensity during PB reduces the risk of DCS, and a larger increase in exercise intensity dramatically reduces risk. These models support the hypothesis that aerobic fitness is an important consideration for the risk of hypobaric DCS when exercise is performed during the PB.

Logistic analysis of OBT dynamics.

PubMed

Baumgaertner, Franz; Yankovich, Tamara L; Kim, Sang Bog

2009-12-01

Formation and depuration of non-exchangeable organically bound tritium (OBT) is measured in mussel dry tissue on expanding time scales. The OBT course of time is analyzed by means of the Verhulst logistic growth function. Two separate routes are found as well for OBT formation as depuration, i.e., restoration of organically bound hydrogen (OBH). Routes which arrive at saturation earlier than sampling started are assigned to respiration. Other routes which start with one-day delay are attributed to metabolc pathways. The metabolic route of OBT formation includes, in addition to the logistic growth function, one rapid mechanism with

Echoguided closed commissurotomy for mitral valve stenosis in a dog.

PubMed

Trehiou-Sechi, Emilie; Behr, Luc; Chetboul, Valérie; Pouchelon, Jean-Louis; Castaignet, Maud; Gouni, Vassiliki; Misbach, Charlotte; Petit, Amandine M P; Borenstein, Nicolas

2011-09-01

Surgical treatment of mitral stenosis (MS) usually consists of open mitral commissurotomy (MC) or percutaneous balloon MC, which require a cardiopulmonary bypass or transseptal approach, respectively. We describe here the first surgical management of congenital MS in a dog using a less invasive procedure, a surgical closed MC under direct echo guidance. A 5-year-old female Cairn terrier was referred for ascites, weakness, and marked exercise intolerance for 2 months, which was refractory to medical treatment. Diagnosis of severe MS associated with atrial fibrillation (AF) was confirmed by echo-Doppler examination and electrocardiography. Poor response to medical treatment suggested a corrective procedure on the valve was indicated. However, due to the cost and high mortality rate associated with cardiopulmonary bypass, a hybrid MC was recommended. A standard left intercostal thoracotomy was performed and three balloon valvuloplasty catheters of differing diameters were sequentially inserted through the left atrium under direct echo guidance. Transesophageal echocardiography revealed a 62% reduction in the pressure half-time compared to the pre-procedure. Thirteen months after surgery the dog is still doing well with resolution of ascites and a marked improvement of most echo-Doppler variables. Copyright © 2011 Elsevier B.V. All rights reserved.

Distribution of ingested americium in chickens and transport to eggs. Final report, 1975

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mullen, A.A.; Lloyd, S.R.; Mosley, R.E.

1976-05-01

The soluble citrate complex of americium-241 was orally administered to 20 white Leghorn laying hens daily for two weeks. The yolks, whites, and shells from the eggs were analyzed for their americium content. Yolk was the only egg fraction in which radioactivity was observed. The americium-241 activity in yolks reached a maximum on the 14th day of dosing. Biological half-times of 2.00 plus or minus 0.18 days and greater than 33 days were indicated by the average concentration values of americium-241 in yolks laid after the maximum activity was reached. The hens were serially sacrificed at 1, 10, and 20more » days after the final administration of americium-241. Tissue samples were collected and the americium content determined in the edible portions and feathers of the hens. Americium was detected in most tissues shortly after dosing; the main concentrations were found in the liver and the skeleton. The highest concentration per organ (3.03 X 0.001 percent of the dose) occurred in the liver of the hens sacrificed 10 days after final administration of americium-241. (GRA)« less

Sequential segmental neuromuscular stimulation reduces fatigue and improves perfusion in dynamic graciloplasty.

PubMed

Zonnevijlle, E D; Somia, N N; Abadia, G P; Stremel, R W; Maldonado, C J; Werker, P M; Kon, M; Barker, J H

2000-09-01

Dynamic graciloplasty is used as a treatment modality for total urinary incontinence caused by a paralyzed sphincter. A problem with this application is undesirable fatigue of the muscle caused by continuous electrical stimulation. Therefore, the neosphincter must be trained via a rigorous regimen to transform it from a fatigue-prone state to a fatigue-resistant state. To avoid or shorten this training period, the application of sequential segmental neuromuscular stimulation (SSNS) was examined. This form of stimulation proved previously to be highly effective in acutely reducing fatigue caused by electrical stimulation. The contractile function and perfusion of gracilis muscles employed as neosphincters were compared between conventional, single-channel, continuous stimulation, and multichannel sequential stimulation in 8 dogs. The sequentially stimulated neosphincter proved to have an endurance 2.9 times longer (as measured by halftime to fatigue) than continuous stimulation and a better blood perfusion during stimulation (both of which were significant changes, p < 0.05). Clinically, this will not antiquate training of the muscle, but SSNS could reduce the need for long and rigorous training protocols, making dynamic graciloplasty more attractive as a method of treating urinary or fecal incontinence.

Case study: three acute 241Am inhalation exposures with DTPA therapy.

PubMed

Carbaugh, Eugene H; Lynch, Timothy P; Cannon, Curt N; Lewis, Loren L

2010-10-01

Three workers incurred inhalation exposures to Am oxide as a result of waste sorting and compaction activities. The exposure magnitudes were not fully recognized until the following day when an in-vivo lung count identified a significant lung deposition of Am in a male worker, and DTPA chelation therapy was initiated. Two additional workers (one female and one male) were then identified as sufficiently exposed to also warrant therapy. In-vivo bioassay measurements were performed over the ensuing 6 mo to quantify the 241Am activity in the lungs, liver, and skeleton. Urine and fecal samples were collected and showed readily detectable 241Am. Clinical lab tests and medical evaluations all showed normal results. There were no significant adverse clinical health effects from the therapy. The estimated 241Am inhalation intakes for the three workers were 1,800 Bq, 630 Bq, and 150 Bq. Lung retention showed somewhat longer pulmonary clearance half-times than standard inhalation class W or absorption Type M assumptions. The three subjects underwent slightly different therapy regimens, with therapy effectiveness factors (defined as the ratio of the reference doses without therapy relative to the final assessed doses) of 4.5, 1.9, and 1.7, respectively.

Effects of solubilization on the inhibition of the p-type ATPase from maize roots by N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline.

PubMed

Brauer, D K; Gurriel, M; Tu, S I

1992-12-01

The biochemical events utilized by transport proteins to convert the chemical energy from the hydrolysis of ATP into an electro-chemical gradient are poorly understood. The inhibition of the plasma membrane ATPase from corn (Zea mays L.) roots by N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ) was compared to that of ATPase solubilized with N-tetradecyl-N,N-dimethyl-3-ammonio-1-propane-sulfonate (3-14) to provide insight into the minimal functional unit. The chromatographic behavior of the 3-14-solubilized ATPase activity during size exclusion chromatography and glycerol gradient centrifugation indicated that the solubilized enzyme was in a monomeric form. Both plasma membrane-bound and solubilized ATPase were inhibited by EEDQ in a time- and concentration-dependent manner consistent with a first-order reaction. When the log of the reciprocal of the half-time for inhibition was plotted as a function of the log of the EEDQ concentration, straight lines were obtained with slopes of approximately 0.5 and 1.0 for membrane-bound and 3-14-solubilized ATPase, respectively, indicating a change in the number of polypeptides per functional ATPase complex induced by solubilization with 3-14.

Mineral induced formation of sugar phosphates

NASA Technical Reports Server (NTRS)

Pitsch, S.; Eschenmoser, A.; Gedulin, B.; Hui, S.; Arrhenius, G.

1995-01-01

Glycolaldehyde phosphate, sorbed from highly dilute, weakly alkaline solution into the interlayer of common expanding sheet structure metal hydroxide minerals, condenses extensively to racemic aldotetrose-2, 4-diphophates, and aldohexose-2, 4, 6-triphosphates. The reaction proceeds mainly through racemic erythrose-2, 4-phosphate, and terminates with a large fraction of racemic altrose-2, 4, 6-phosphate. In the absence of an inductive mineral phase, no detectable homogeneous reaction takes place in the concentration- and pH range used. The reactant glycolaldehyde phosphate is practically completely sorbed within an hour from solutions with concentrations as low as 50 micron; the half-time for conversion to hexose phosphates is of the order of two days at room temperature and pH 9.5. Total production of sugar phosphates in the mineral interlayer is largely independent of the glycolaldehyde phosphate concentration in the external solution, but is determined by the total amount of GAP offered for sorption up to the capacity of the mineral. In the presence of equimolar amounts of rac-glyceraldehyde-2-phosphate, but under otherwise similar conditions, aldopentose-2, 4, -diphosphates also form, but only as a small fraction of the hexose-2, 4, 6-phosphates.

Use of radiation protraction to escalate biologically effective dose to the treatment target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuperman, V. Y.; Spradlin, G. S.; Department of Mathematics, Embry-Riddle University, Daytona Beach, Florida 32114

2011-12-15

Purpose: The aim of this study is to evaluate how simultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target (BED{sub tar}) while biologically effective dose for the normal tissue (BED{sub nt}) is fixed. Methods: In this investigation, BED{sub tar} and BED{sub nt} were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results: Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BED{sub tar} while BED{sub nt} is fixed. The dependence of biologically effective dose on fraction time is influenced bymore » the dose rate. In this investigation we analytically determined time-varying dose rate R-tilde which minimizes BED. Changes in BED with fraction time were compared for constant dose rate and for R-tilde. Conclusions: A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.« less

Carboxyhaemoglobin and pulmonary epithelial permeability in man.

PubMed Central

Jones, J G; Minty, B D; Royston, D; Royston, J P

1983-01-01

The effect of cigarette smoke exposure on pulmonary epithelial permeability was studied in 45 smokers and 22 non-smokers. An index of cigarette smoke exposure was obtained from the carboxyhaemoglobin concentration (HbCO%). Pulmonary epithelial permeability was proportional to the half-time clearance rate of technetium-99m-labelled diethylene triamine pentacetate (99mTc DTPA) from lung to blood (T1/2LB). The relationship between T1/2LB and HbCO% was hyperbolic in form and the data could be fitted to the quadratic formula (formula; see text) where the parameters a0, a1, and a2 represent respectively the asymptotic T1/2LB value at large carboxyhaemoglobin values and the slope and shape of the curve. The values of these parameters were a0 4.4 (2.6), a1 = 77.8 (15.5), and a2 -25.5 (9.7) (SE). This is the first demonstration of a dose-response relationship between carboxyhaemoglobin and an increased permeability of the lungs in man and provides a technique for identifying the roles of carbon monoxide and other cigarette smoke constituents in causing increased pulmonary epithelial permeability. PMID:6344310

Simultaneous quantification of actin monomer and filament dynamics with modeling-assisted analysis of photoactivation

PubMed Central

Kapustina, Maryna; Read, Tracy-Ann

2016-01-01

ABSTRACT Photoactivation allows one to pulse-label molecules and obtain quantitative data about their behavior. We have devised a new modeling-based analysis for photoactivatable actin experiments that simultaneously measures properties of monomeric and filamentous actin in a three-dimensional cellular environment. We use this method to determine differences in the dynamic behavior of β- and γ-actin isoforms, showing that both inhabit filaments that depolymerize at equal rates but that β-actin exists in a higher monomer-to-filament ratio. We also demonstrate that cofilin (cofilin 1) equally accelerates depolymerization of filaments made from both isoforms, but is only required to maintain the β-actin monomer pool. Finally, we used modeling-based analysis to assess actin dynamics in axon-like projections of differentiating neuroblastoma cells, showing that the actin monomer concentration is significantly depleted as the axon develops. Importantly, these results would not have been obtained using traditional half-time analysis. Given that parameters of the publicly available modeling platform can be adjusted to suit the experimental system of the user, this method can easily be used to quantify actin dynamics in many different cell types and subcellular compartments. PMID:27831495

Peptidase activity as a determinant of agonist potencies in some smooth muscle preparations.

PubMed

Hall, J M; Fox, A J; Morton, I K

1990-02-06

The influence of degradation by peptidases on concentration-response relationships for peptide agonists of the tachykinin and bombesin-like families was investigated. The combined presence of three peptidase inhibitors, phosphoramidon (1 microM), captopril (1 microM) and bestatin (100 microM), had no significant effect on the onset rates or peak contractile responses to these peptides in the rat urinary bladder and guinea-pig taenia caeci preparations, or on their peak potentiation of the contractile response to field-stimulation in the guinea-pig vas deferens preparation. However, rates of offset of the response to tachykinins were markedly prolonged in tissues treated with peptidase inhibitors. In experiments designed to estimate clearance of applied peptide from the organ bath, there was an initial rate of loss with the guinea-pig vas deferens and taenia caeci which, measured over the first 5 min, had a half-time of 2-3 min which was then prolonged to 6-8 min in the presence of peptidase inhibitors. These results show that although peptide breakdown can be demonstrated in these systems, it seems not to be an important determinant of relative pharmacological activity measured in terms of peak response.

Kinetic energy definition in velocity Verlet integration for accurate pressure evaluation.

PubMed

Jung, Jaewoon; Kobayashi, Chigusa; Sugita, Yuji

2018-04-28

In molecular dynamics (MD) simulations, a proper definition of kinetic energy is essential for controlling pressure as well as temperature in the isothermal-isobaric condition. The virial theorem provides an equation that connects the average kinetic energy with the product of particle coordinate and force. In this paper, we show that the theorem is satisfied in MD simulations with a larger time step and holonomic constraints of bonds, only when a proper definition of kinetic energy is used. We provide a novel definition of kinetic energy, which is calculated from velocities at the half-time steps (t - Δt/2 and t + Δt/2) in the velocity Verlet integration method. MD simulations of a 1,2-dispalmitoyl-sn-phosphatidylcholine (DPPC) lipid bilayer and a water box using the kinetic energy definition could reproduce the physical properties in the isothermal-isobaric condition properly. We also develop a multiple time step (MTS) integration scheme with the kinetic energy definition. MD simulations with the MTS integration for the DPPC and water box systems provided the same quantities as the velocity Verlet integration method, even when the thermostat and barostat are updated less frequently.

Impotence evaluated by the use of prostaglandin E1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, T.I.; Yang, C.R.; Wang, S.J.

1989-06-01

We screened 80 patients at our hospital for the differential diagnosis of impotence using intracavernous injection of prostaglandin E1 (20 micrograms). The rate of positive response was 78.8 per cent (63 patients). Neither systemic reactions nor priapism occurred. However, a considerable incidence (23.8 per cent, 19 of 80 patients) of tolerable injection pain was encountered. The 133-xenon penile washout study was conducted routinely in impotent men for hemodynamic evaluation of penile vascularity. In 80 patients a positive correlation between the response of intracavernous prostaglandin E1 injection and the result of the washout study was found (r equals 0.381, p lessmore » than 0.0002). We selected 14 subjects randomly to receive additional intravenous infusions of prostaglandin E1 (6 ampules, 120 micrograms total) for 3 days, after which another 133-xenon washout study was done. The washout studies before and after intravenous prostaglandin E1 infusion were compared, and 10 patients (71.4 per cent) appeared to obtain improvement in half-time clearance and penile blood flow. However, only 3 patients noticed improvement subjectively. We suggest that prostaglandin E1 could be a desirable alternative for the diagnosis and treatment of impotence.« less

Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm.

PubMed

Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Watson, Randy D

2004-01-01

The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean (+/-SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%+/-31%) than in controls (61%+/-36%) and the opioid group (61%+/-25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%+/-4% in the opioid group; this was significantly lower (P<0.0001) than the values in the control group (54%+/-18%) and the SOS group (48%+/-29%). Almost all of the bile emptied from the gallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling) in all eight patients with SOS, but in none of the patients in the other two groups. Mean paradoxical filling was 204% (+/-193%) in the SOS group and less than 5% (P<0.05) in both the control and the opioid group. After treatment, six of the SOS patients had complete pain relief and one, partial pain relief. The basal tonus of the sphincter is variable in patients with SOS, and allows relatively more of the hepatic bile to enter the GI tract than the gallbladder. Due to simultaneous contraction of the sphincter and gallbladder in response to CCK-8, most of the bile emptied from the gallbladder refluxes into intrahepatic ducts, and reenters the gallbladder immediately after cessation of hormone infusion. The characteristic features of gallbladder filling, emptying, and paradoxical refilling with cholecystokinin provide objective parameters for noninvasive diagnosis of SOS by quantitative cholescintigraphy.

Implications of human tissue studies for radiation protection.

PubMed

Kathren, R L

1988-08-01

Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant 241Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for 238Pu and 241Am and the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices.

Does management really work?

PubMed

Bloom, Nicholas; Sadun, Raffaella; Van Reenen, John

2012-11-01

HBR's 90th anniversary is a sensible time to revisit a basic question: Are organizations more likely to succeed if they adopt good management practices? The answer may seem obvious to most HBR readers, but these three economists cast their net much wider than that. In a decadelong study of thousands of organizations in 20 countries, they and their interview teams assessed how well manufacturers, schools, and hospitals adhere to three management basics: targets, incentives, and monitoring. They found that huge numbers of companies follow none of those fundamentals, that adopting the basics yields big improvements in outcomes such as productivity and longevity, and that good nuts-and-bolts management at individual firms shapes national performance. At 14 textile manufacturers in India, for example, an intervention--involving free, high-quality advice from a consultant who was on-site half-time for five months--cut defects by half, reduced inventory by 20%, and raised output by 10%. A control group saw no such gains. The authors' global data set suggests that implementing good management at schools and hospitals yields change more slowly than at manufacturers--but it does come eventually. And the macroeconomic potential--for incomes, productivity, and delivery of critically needed services--is huge. A call for "better management" may sound prosaic, but given the global payoffs, it's actually quite radical.

Physical and physiological demands of U-19 basketball refereeing: Aerobic and anaerobic demands.

PubMed

Nabli, Mohamed Ali; Ben Abdelkrim, Nidhal; Castagna, Carlo; Jabri, Imed; Batikh, Tahar; Chamari, Karim

2016-01-01

This study aimed to examine the physical and physiological demands of basketball refereeing. 16 elite-level basketball referees were studied during U-19 basketball games (n=8) for time-motion analyses, exercise heart rates (HR) and blood lactate concentration [La]. Game activities were considered as time spent and distance covered in five locomotors activities (standing, walking, jogging, running and sprinting). Referees spent more time (p<0.01) walking (63.72±2.02 min) than jogging (3.10±0.29 min), running (4.24±0.46 min) and sprinting (1.69±0.24 min). Referees covered more distance (p<0.01) walking than jogging, running and sprinting across the quarters (Q). Mean HR (74.89±6.86 %HRmax) was not significantly different across the game Q (Q1 to Q4) and halves. [La] did not show significant changes (p=0.221) when comparing the half-time (4.30±3.92 mmol.L(-1)) and the end of the game (6.70±4.90 mmol.L(-1)). In light of this study, we conclude that U-19 basketball refereeing is a moderate intensity activity where referees spent 81% of total game time at low-intensity with bouts of high-intensity activities throughout the game.

Three-dimensional echocardiographic assessment of the repaired mitral valve.

PubMed

Maslow, Andrew; Mahmood, Feroze; Poppas, Athena; Singh, Arun

2014-02-01

This study examined the geometric changes of the mitral valve (MV) after repair using conventional and three-dimensional echocardiography. Prospective evaluation of consecutive patients undergoing mitral valve repair. Tertiary care university hospital. Fifty consecutive patients scheduled for elective repair of the mitral valve for regurgitant disease. Intraoperative transesophageal echocardiography. Assessments of valve area (MVA) were performed using two-dimensional planimetry (2D-Plan), pressure half-time (PHT), and three-dimensional planimetry (3D-Plan). In addition, the direction of ventricular inflow was assessed from the three-dimensional imaging. Good correlations (r = 0.83) and agreement (-0.08 +/- 0.43 cm(2)) were seen between the MVA measured with 3D-Plan and PHT, and were better than either compared to 2D-Plan. MVAs were smaller after repair of functional disease repaired with an annuloplasty ring. After repair, ventricular inflow was directed toward the lateral ventricular wall. Subgroup analysis showed that the change in inflow angle was not different after repair of functional disease (168 to 171 degrees) as compared to those presenting with degenerative disease (168 to 148 degrees; p<0.0001). Three-dimensional imaging provides caregivers with a unique ability to assess changes in valve function after mitral valve repair. Copyright © 2014 Elsevier Inc. All rights reserved.

Concordance Between Clinical Practice and Published Evidence: Findings From Virginia Commonwealth University School of Dentistry.

PubMed

Chiang, Harmeet K; Best, Al M; Sarrett, David C

2017-09-01

To evaluate the concordance between clinical practice and published evidence by dental faculty and graduating students of the Virginia Commonwealth University School of Dentistry. A questionnaire previously developed by the National Dental Practice-Based Research Network with 12 clinical scenarios was administered to VCU faculty and graduating students. Responses were scored as either consistent or inconsistent with published evidence and then analyzed for differences between dental faculty, graduating students, and the national results. There were 43 dental faculty members with at least half-time student contact who responded to the survey. Faculty concordance ranged from 33% to 100%, and general practice faculty had the highest concordance (82%). Eighty-five of the graduating class of 98 responded to the survey, and student concordance ranged from 18% to 92% and averaged 67%. General practice faculty had higher concordance with published evidence than recently graduated dental students. Graduating students and dental faculty demonstrated higher concordance with evidence-based practice than practitioners in the National Dental Practice-Based Research Network. General practice dental faculty demonstrated adequate concordance, but students demonstrated only a medium-level concordance. Practitioners involved in teaching dental students are better able to keep up with evolving evidence and are better able to demonstrate evidence-based practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Rising intracellular zinc by membrane depolarization and glucose in insulin-secreting clonal HIT-T15 beta cells.

PubMed

Slepchenko, Kira G; Li, Yang V

2012-01-01

Zinc (Zn(2+)) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30-60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

Sediment transport and Hg recovery in Lavaca Bay, as evaluated from radionuclide and Hg distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santschi, P.H.; Allison, M.A.; Asbill, S.

1999-02-01

Mercury was released in the late 1960s from a chloralkali facility managed by ALCOA and deposited into sediments of Lavaca Bay, TX. Sediments have recorded this event as a well-defined subsurface concentration maximum. Radionuclide, mercury, X-radiography, and grain size data from sediment cores taken in 1997 at 15 stations in Lavaca bay were used to assess sediment and Hg movements in the bay. Sediment accumulation rates were calculated from bomb fallout nuclide ({sup 137}Cs, {sup 239,240}Pu) peaks in 1963 and from the steady-state delivery of {sup 210}Pb from the atmosphere. Sedimentation rates are highest at near-shore sites near the ALCOAmore » facility and generally decrease away from shore. Sedimentation rates in some areas are likely influenced by anthropogenic activities such as dredging. Particle reworking, as assessed from {sup 7}Be measurements, is generally restricted to the upper 2--7 cm of sediments. Numerical simulations of Hg profiles using measured sedimentation and mixing parameters indicate that at most sites high remnant mercury concentrations at 15--60 cm depth cannot supply substantial amounts of Hg to surface sediments. Assuming no future Hg supplies, Hg concentrations in surface sediments are predicted to decrease exponentially with a recovery half-time of 4 {+-} 2 years.« less

Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol☆

PubMed Central

Wallace, Anne M.; Hoh, Carl K.; Limmer, Karl K.; Darrah, Denise D.; Schulteis, Gery; Vera, David R.

2014-01-01

Lymphoseek is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node (SLN) mapping. We conducted a clinical trial which measured the injection site clearance and sentinel lymph node accumulation after a single intradermal injection of Lymphoseek or unfiltered [99mTc]sulfur colloid (TcSC) using a “2-day” protocol for SLN mapping of breast cancer. Eleven patients with breast cancer participated in this study. Five patients received an intradermal administration of 1.0 nmol of 99mTc-labeled Lymphoseek; SLN mapping was performed on four subjects within 19 to 27 h. Six subjects received an intradermal administration of TcSC; SLN mapping was performed on five subjects within 18 to 26 h. Lymphoseek exhibited a significantly (P<.001) faster injection site clearance than TcSC. The mean Lymphoseek clearance half-time was 2.18±1.09 h compared to 57.4±92.8 h for TcSC. The mean sentinel lymph node uptake of Lymphoseek (1.5±1.7%) and TcSC (3.5±3.1%) was statistically equivalent (P=.213). When an intradermal injection is employed, Lymphoseek demonstrated faster injection site clearance than unfiltered [99mTc]sulfur colloid and persistent SLN accumulation for at least 24 h. PMID:19647175

BCAS2 interacts with HSF4 and negatively regulates its protein stability via ubiquitination.

PubMed

Liao, Shengjie; Du, Rong; Wang, Lei; Qu, Zhen; Cui, Xiukun; Li, Chang; Liu, Fei; Huang, Mi; Wang, Jiuxiang; Chen, Jiaxiang; Gao, Meng; Yu, Shanshan; Tang, Zhaohui; Li, David Wan-Cheng; Jiang, Tao; Liu, Mugen

2015-11-01

Heat shock factor 4 (HSF4) is an important transcriptional factor that plays a vital role in lens development and differentiation, but the mechanism underlying the regulation of HSF4 is ambiguous. BCAS2 was reported to be an essential subunit of pre-mRNA splicing complex. Here, we identified BCAS2 as a novel HSF4 interacting partner. High expression of BCAS2 in the lens epithelium cells and the bow region of mouse lens was detected by immunohistochemistry. In human lens epithelial cells, BCAS2 negatively regulates HSF4 protein level and transcriptional activity, whereas in BCAS2 knockdown cells, HSF4 protein stability was increased significantly. We further demonstrated that the prolonged protein half-time of HSF4 in BCAS2 knockdown cells was due to reduced ubiquitination. Moreover, we have identified the lysine 206 of HSF4 as the key residue for ubiquitination. The HSF4-K206R mutant blocked the impact of BCAS2 on HSF4 protein stability. Taken together, we identified a pathway for HSF4 degradation through the ubiquitin-proteasome system, and a novel function for BCAS2 that may act as a negative regulatory factor for modulating HSF4 protein homeostasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Implications of human tissue studies for radiation protection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathren, R.L.

1988-08-01

Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant /sup 241/Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for /sup 238/Pu and /sup 241/Am andmore » the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices.« less

Carbon Nanotubes in the Human Respiratory Tract-Clearance Modeling.

PubMed

Sturm, Robert

2017-03-01

Clearance of single-wall carbon nanotubes (SWCNT, diameter: 5 nm) and multi-wall carbon nanotubes (MWCNT, diameter: 50 nm) in the respiratory tract was predicted for various age groups (infants, children, adolescents, and adults). The model was founded on the assumption that lung clearance takes place in three distinct phases: (i) fast mucociliary clearance, (ii) slow bronchial clearance, and (iii) alveolar clearance. To each of these phases a specific fraction of deposited particles was attributed, the amount of which depended on particles' geometry and particles' deposition sites in the respiratory system. Clearance velocities were expressed by respective clearance half-times ranging from several hours in the case of fast clearance to tens of days in the case of slow clearance. Results of the simulations clearly demonstrate that for the specific deposition scenario (sitting, nasal breathing) considered here fast clearance fraction exhibits a slight decrease with increasing age, but total clearance times (i.e. time spans, within which 100% of the deposited particulate mass are removed) are rather constant among the age groups. Nanotubes deposited in the respiratory bronchioles and alveoli are usually subject to a long-term storage in these structures and, thus, may trigger malignant transformations in adjacent cells and tissues. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Solubility classification of airborne uranium products collected at the perimeter of the Allied Chemical Plant, Metropolis, Illinois

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalkwarf, D.R.

1980-05-01

Airborne uranium products were collected at the perimeter of the uranium-conversion plant operated by the Allied Chemical Corporation at Metropolis, Illinois, and the dissolution rates of these products were classified in terms of the ICRP Task Group Lung Model. Assignments were based on measurements of the dissolution half-times exhibited by uranium components of the dust samples as they dissolved in simulated lung fluid at 37/sup 0/C. Based on three trials, the dissolution behavior of dust with aerodynamic equivalent diameter (AED) less than 5.5 ..mu..m and collected nearest the closest residence to the plant was classified 0.40 D, 0.60 Y. Basedmore » on two trials, the dissolution behavior of dust with AED greater than 5.5 ..mu..m and collected at this location was classified 0.37 D, 0.63 Y. Based on one trial, the dissolution behavior of dust with AED less than 5.5 ..mu..m and collected at a location on the opposite side of the plant was classified 0.68 D, 0.32 Y. There was some evidence for adsorption of dissolved uranium onto other dust components during dissolution, and preliminary dissolution trials are recommended for future samples in order to optimize the fluid replacement schedule.« less

On the influence of DC electric fields on the aerosol assisted chemical vapor deposition growth of photoactive titanium dioxide thin films.

PubMed

Romero, Luz; Binions, Russell

2013-11-05

Titanium dioxide thin films were deposited on fluorine doped tin oxide glass substrate from the electric field assisted aerosol chemical vapor deposition (EACVD) reaction of titanium isopropoxide (TTIP, Ti(OC3H7)4) in toluene on glass substrates at a temperature of 450 °C. DC electric fields were generated by applying a potential difference between the electrodes of the transparent coated oxide coated glass substrates during the deposition. The deposited films were characterized using scanning electron microscopy, X-ray diffraction, atomic force microscopy, Raman spectroscopy, and UV-vis spectroscopy. The photoactivity and hydrophilicity of the deposited films were also analyzed using a dye-ink test and water-contact angle measurements. The characterization work revealed that the incorporation of DC electric fields produced significant reproducible changes in the film microstructure, preferred crystallographic orientation, roughness, and film thickness. Photocatalytic activity was calculated from the half-time (t1/2) or time taken to degrade 50% of the initial resazurin dye concentration. A large improvement in photocatalytic activity was observed for films deposited using an electric field with a strong orientation in the (004) direction (t1/2 17 min) as compared to a film deposited with no electric field (t1/2 40 min).

Synthesis, isolation and purification of [11C]-choline

PubMed Central

Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

2016-01-01

[11C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [11C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [11C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [11C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [11C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [11C]-target containing cyclotron. PMID:27660552

High- and Low-mobility Populations of HP1 in Heterochromatin of Mammalian CellsD⃞

PubMed Central

Schmiedeberg, Lars; Weisshart, Klaus; Diekmann, Stephan; Meyer zu Hoerste, Gabriele; Hemmerich, Peter

2004-01-01

Heterochromatin protein 1 (HP1) is a conserved nonhistone chromosomal protein with functions in euchromatin and heterochromatin. Here we investigated the diffusional behaviors of HP1 isoforms in mammalian cells. Using fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP) we found that in interphase cells most HP1 molecules (50–80%) are highly mobile (recovery halftime: t1/2 ≈ 0.9 s; diffusion coefficient: D ≈ 0.6–0.7 μm2 s-1). Twenty to 40% of HP1 molecules appear to be incorporated into stable, slow-moving oligomeric complexes (t1/2 ≈ 10 s), and constitutive heterochromatin of all mammalian cell types analyzed contain 5–7% of very slow HP1 molecules. The amount of very slow HP1 molecules correlated with the chromatin condensation state, mounting to more than 44% in condensed chromatin of transcriptionally silent cells. During mitosis 8–14% of GFP-HP1α, but not the other isoforms, are very slow within pericentromeric heterochromatin, indicating an isoform-specific function of HP1α in heterochromatin of mitotic chromosomes. These data suggest that mobile as well as very slow populations of HP1 may function in concert to maintain a stable conformation of constitutive heterochromatin throughout the cell cycle. PMID:15064352

Assimilation and regeneration of trace elements by marine copepods

USGS Publications Warehouse

Wang, W.-X.; Reinfelder, J.R.; Lee, B.-G.; Fisher, N.S.

1996-01-01

Assimilation efficiencies (AE) of five trace elements (Am, Cd, Co, Se, and Zn) and carbon by neritic copepods (Acartia tonsa and Temora longicornis) feeding at different food concentrations and on different food types (diatoms, green algae, flagellates, dinoflagellates, and Fe oxides) were measured with radiotracer techniques. Food concentration had little influence on AEs of C, Cd, Co, and Se within a range of 16-800 ?? C liter-1. AEs of Am and Zn were highest at low food concentrations (16-56 ??g C liter-1) but remained relatively constant when food levels exceeded 160 ??g C liter-1. Different algal diets had no major influence on AEs, which generally were in the order Cd > Se > Zn > Co > Am. Metals (Cd, Co, and Zn) were assimilated from Fe oxides with 50% less efficiency than from algal cells. Element regeneration into the dissolved phase was a significant route for the release of ingested elements by copepods and increased with increased food concentration. Element regeneration rates for Cd, Se, and Zn were comparable to the regeneration rates of major nutrients such as P (30-70% daily). Retention half-times of elements in decomposing fecal pellets ranged from 10 d (Am). The efficient assimilation and regeneration of Cd, Se, and Zn can significantly lengthen the residence time of these elements in ocean surface waters.

Successful surgical treatment of mitral valve stenosis in a dog.

PubMed

Borenstein, N; Daniel, P; Behr, L; Pouchelon, J L; Carbognani, D; Pierrel, A; Macabet, V; Lacheze, A; Jamin, G; Carlos, C; Chetboul, V; Laborde, F

2004-01-01

To report the successful surgical management (open mitral commissurotomy, OMC) of mitral stenosis (MS), incorporating heart-beating cardiopulmonary bypass (CPB), in a 1-year-old dog. Clinical case. One-year-old Cairn Terrier with MS. Diagnosis of MS was confirmed by means of 2-dimensional, continuous-wave and color-flow Doppler echocardiography. Surgery was performed through a left intercostal thoracotomy. CPB was initiated and the heart was kept beating. The fused commissures of the mitral valve were incised to free the cusps of the valve. Left intercostal thoracotomy allowed easy observation of the mitral orifice during heart-beating OMC. Persistent bleeding from the atriotomy site required a second surgical procedure after which the dog had an uneventful recovery. Echocardiography at 2 weeks and 1 year postoperatively indicated substantial improvement in left ventricular filling (pressure half-time=187 ms before surgery, 105 ms [2 weeks] and 110 ms [1 year] after surgery). Enlargement of the left atrium resolved; however, moderate mitral valve regurgitation was still present. MS can be successfully treated by OMC, facilitated by use of CPB. Substantial improvement in cardiac function was evident by ultrasound and Doppler examination postoperatively. OMC under heart-beating CPB should be considered for the treatment of MS in the dog.

Mitral stenosis in 15 dogs.

PubMed

Lehmkuhl, L B; Ware, W A; Bonagura, J D

1994-01-01

Mitral stenosis was diagnosed in 15 young to middle-aged dogs. There were 5 Newfoundlands and 4 bull terriers affected, suggesting a breed predisposition for this disorder. Clinical signs included cough, dyspnea, exercise intolerance, and syncope. Soft left apical diastolic murmurs were heard only in 4 dogs, whereas 8 dogs had systolic murmurs characteristic of mitral regurgitation. Left atrial enlargement was the most prominent radiographic feature. Left-sided congestive heart failure was detected by radiographs in 11 dogs within 1 year of diagnosis. Electrocardiographic abnormalities varied among dogs and included atrial and ventricular enlargement, as well as atrial and ventricular arrhythmias. Abnormalities on M-mode and two-dimensional echocardiograms included abnormal diastolic motion of the mitral valve characterized by decreased leaflet separation, valve doming, concordant motion of the parietal mitral valve leaflet, and a decreased E-to-F slope. Increased mitral valve inflow velocities and prolonged pressure half-times were detected by Doppler echocardiography. Cardiac catheterization, performed in 8 dogs, documented a diastolic pressure gradient between the left atrial, pulmonary capillary wedge, or pulmonary artery diastolic pressures and the left ventricular diastolic pressure. Necropsy showed mitral stenosis caused by thickened, fused mitral valve leaflets in 5 dogs and a supramitral ring in another dog. The outcome in affected dogs was poor; 9 of 15 dogs were euthanatized or died by 2 1/2 years of age.

Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viability.

PubMed

Carrapita, Jorge; Abrantes, Ana Margarida; Campelos, Sofia; Gonçalves, Ana Cristina; Cardoso, Dulce; Sarmento-Ribeiro, Ana Bela; Rocha, Clara; Santos, Jorge Nunes; Botelho, Maria Filomena; Tralhão, José Guilherme; Farges, Olivier; Barbosa, Jorge Maciel

2016-10-11

It was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours.

Specialization of the auditory processing in harbor porpoise, characterized by brain-stem potentials

NASA Astrophysics Data System (ADS)

Bibikov, Nikolay G.

2002-05-01

Brain-stem auditory evoked potentials (BAEPs) were recorded from the head surface of the three awaked harbor porpoises (Phocoena phocoena). Silver disk placed on the skin surface above the vertex bone was used as an active electrode. The experiments were performed at the Karadag biological station (the Crimea peninsula). Clicks and tone bursts were used as stimuli. The temporal and frequency selectivity of the auditory system was estimated using the methods of simultaneous and forward masking. An evident minimum of the BAEPs thresholds was observed in the range of 125-135 kHz, where the main spectral component of species-specific echolocation signal is located. In this frequency range the tonal forward masking demonstrated a strong frequency selectivity. Off-response to such tone bursts was a typical observation. An evident BAEP could be recorded up to the frequencies 190-200 kHz, however, outside the acoustical fovea the frequency selectivity was rather poor. Temporal resolution was estimated by measuring BAER recovery functions for double clicks, double tone bursts, and double noise bursts. The half-time of BAERs recovery was in the range of 0.1-0.2 ms. The data indicate that the porpoise auditory system is strongly adapted to detect ultrasonic closely spaced sounds like species-specific locating signals and echoes.

Characterization of bioimprinted tannase and its kinetic and thermodynamics properties in synthesis of propyl gallate by transesterification in anhydrous medium.

PubMed

Nie, Guangjun; Zheng, Zhiming; Gong, Guohong; Zhao, Genhai; Liu, Yan; Song, Junying; Dai, Jun

2012-08-01

Tannase has been extensively applied to synthesize gallic acid esters. Bioimprinting technique can evidently enhance transesterification-catalyzing performance of tannase. In order to promote the practical utilization of the modified tannase, a few enzymatic characteristics of the enzyme and its kinetic and thermodynamics properties in synthesis of propyl gallate by transesterification in anhydrous medium have been studied. The investigations of pH and temperature found that the imprinted tannase holds an optimum activity at pH 5.0 and 40 °C. On the other hand, the bioimprinting technique has a profound enhancing effect on the adapted tannase in substrate affinity and thermostability. The kinetic and thermodynamic analyses showed that the modified tannase has a longer half-time of 1,710 h at 40 °C; the kinetic constants, the activation energy of reversible thermal inactivation, and the activation energy of irreversible thermal inactivation, respectively, are 0.054 mM, 17.35 kJ mol(-1), and 85.54 kJ mol(-1) with tannic acid as a substrate at 40 °C; the free energy of Gibbs (ΔG) and enthalpy (ΔH) were found to be 97.1 and 82.9 kJ mol(-1) separately under the same conditions.

System analysis of the dynamic response of the coronary circulation to a sudden change in heart rate.

PubMed

Dankelman, J; Stassen, H G; Spaan, J A

1990-03-01

In this study the response of driving pressure/flow ration on an abrupt change in heart rate was analysed. The difference between the response obtained with constant pressure and constant flow perfusion was also studied. The responses show a fast initial reversed phase followed by a slow phase caused by regulation. To test whether the initial phase could be the result of mechanical changes in the coronary circulation, a model for regulation was extended by the addition of four different mechanical models originating from the literature. These extended models were able to explain the fast initial phase. However, the mechanical model consisting of an intramyocardial compliance (C = 0.08 ml mm Hg-1 100 g-1) with a variable venous resistance, and the model consisting of a waterfall and a small compliance (C = 0.007 ml mm Hg-1 100g-1) both explained these responses best. The analysis showed that there is no direct relationship between rate of change of vascular tone and rate of change of pressure/flow ratio. However, on the basis of the two extended models, it can be predicted that the half-time for the response of regulation to be complete is about 9s with constant pressure perfusion and 15 s with constant flow perfusion.

Body-Cooling Paradigm in Sport: Maximizing Safety and Performance During Competition.

PubMed

Adams, William M; Hosokawa, Yuri; Casa, Douglas J

2016-12-01

Although body cooling has both performance and safety benefits, knowledge on optimizing cooling during specific sport competition is limited. To identify when, during sport competition, it is optimal for body cooling and to identify optimal body-cooling modalities to enhance safety and maximize sport performance. A comprehensive literature search was conducted to identify articles with specific context regarding body cooling, sport performance, and cooling modalities used during sport competition. A search of scientific peer-reviewed literature examining the effects of body cooling on exercise performance was done to examine the influence of body cooling on exercise performance. Subsequently, a literature search was done to identify effective cooling modalities that have been shown to improve exercise performance. The cooling modalities that are most effective in cooling the body during sport competition depend on the sport, timing of cooling, and feasibility based on the constraints of the sports rules and regulations. Factoring in the length of breaks (halftime substitutions, etc), the equipment worn during competition, and the cooling modalities that offer the greatest potential to cool must be considered in each individual sport. Scientific evidence supports using body cooling as a method of improving performance during sport competition. Developing a strategy to use cooling modalities that are scientifically evidence-based to improve performance while maximizing athlete's safety warrants further investigation.

Measurement of contaminant removal from skin using a portable fluorescence scanning system.

PubMed

Hession, Helena; Byrne, Miriam; Cleary, S; Andersson, K G; Roed, J

2006-01-01

The residence time of particulate contamination on the human body is a factor that has an important impact on the accuracy of exposure assessment in the aftermath of an accidental release of radionuclides to the atmosphere. Measurements of particle clearance from human skin were made using an illumination system to excite fluorescence in labelled silica particles and a CCD camera and image processing system to detect this fluorescence. The illumination system consists of high-intensity light emitting diodes (LEDS) of suitable wavelengths arranged on a portable stand. The physically small size of the LEDs allows them to be positioned close to the fluorescing surface, thus maximising the fluorescent signal that can be obtained. The limit of detection was found to be 50 microg of tracer particle per cm2. Experiments were carried out to determine the clearance rates of 10 microm and 3 microm particles from the skin. Results show that, in the absence of any mechanical rubbing of the skin, the clearance of particles from the skin followed an approximately exponential decay with a half-time of 1.5-7.8 h. Skin hairiness and degree of human movement were found, in addition to particle size, to have an important influence on particle fall-off rate.

The antiproliferative cytostatic effects of a self-activating viridin prodrug

PubMed Central

Smith, Adam; Blois, Joseph; Yuan, Hushan; Aikawa, Elena; Ellson, Christian; Figueiredo, Jose-Luiz; Weissleder, Ralph; Kohler, Rainer; Yaffe, Michael B.; Cantley, Lewis C.; Josephson, Lee

2009-01-01

Although viridins like wortmannin (Wm) have long been examined as anticancer agents, their ability to self-activate has only recently been recognized. Here, we describe the cytostatic effects of a self-activating viridin (SAV), which is an inactive, polymeric prodrug. SAV self-activates to generate a bioactive, fluorescent viridin NBD-Wm with a half-time of 9.2 hours. With cultured A549 cells, 10 µmol/L SAV caused growth arrest without inducing apoptosis or cell death, a cytostatic action markedly different from other chemotherapeutic agents (vinblastine, camptothecin, and paclitaxel). In vivo, a SAV dosing of 1 mg/kg once in 48 hours (i.p.) resulted in growth arrest of an A549 tumor xenograft, with growth resuming when dosing ceased. With a peak serum concentration of SAV of 2.36 µmol/L (at 2 hours post i.p. injection), the concentration of bioactive NBD-Wm was 41 nmol/L based on the partial inhibition of neutrophil respiratory burst. Therefore, SAV was present as an inactive prodrug in serum (peak = 2.36 µmol/L), which generated low concentrations of active viridin (41 nmol/L). SAV is a prodrug, the slowrelease and cytostatic activities of which suggest that it might be useful as a component of metronomic-based chemotherapeutic strategies. PMID:19509266

Uranium in bone: metabolic and autoradiographic studies in the rat.

PubMed

Priest, N D; Howells, G R; Green, D; Haines, J W

1982-03-01

The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1 Uranium is initially deposited onto all types of bone surface, but preferentially onto those that are accreting. 2 Uranium is deposited in the calcifying zones of skeletal cartilage. 3 Bone accretion results in the burial of surface deposits of uranium. 4 Bone resorption causes the removal of uranium from surfaces. 5 Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6 Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7 The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium.

Gas exchange kinetics following concentric-eccentric isokinetic arm and leg exercise.

PubMed

Drescher, U; Mookerjee, S; Steegmanns, A; Knicker, A; Hoffmann, U

2017-06-01

To evaluate the effects of exercise velocity (60, 150, 240deg∙s -1 ) and muscle mass (arm vs leg) on changes in gas exchange and arterio-venous oxygen content difference (avDO 2 ) following high-intensity concentric-eccentric isokinetic exercise. Fourteen subjects (26.9±3.1years) performed a 3×20-repetition isokinetic exercise protocol. Recovery beat-to-beat cardiac output (CO) and breath-by-breath gas exchange were recorded to determine post-exercise half-time (t 1/2 ) for oxygen uptake (V˙O 2 pulm), carbon dioxide output (V˙CO 2 pulm), and ventilation (V˙ E ). Significant differences of the t 1/2 values were identified between 60 and 150deg∙s -1 . Significant differences in the t 1/2 values were observed between V˙O 2 pulm and V˙CO 2 pulm and between V˙CO 2 pulm and V˙ E . The time to attain the first avDO 2 -peak showed significant differences between arm and leg exercise. The present study illustrates, that V˙O 2 pulm kinetics are distorted due to non-linear CO dynamics. Therefore, it has to be taken into account, that V˙O 2 pulm may not be a valuable surrogate for muscular oxygen uptake kinetics in the recovery phases. Copyright © 2017 Elsevier B.V. All rights reserved.

Noise amplification of plant gravisensing

NASA Astrophysics Data System (ADS)

Ma, Zhong; Hasenstein, Karl H.

A common problem in sensory physiology is the detection of weak signals, such as that produced by the repositioning of statoliths (amyloplasts) in gravisensing cells, from a noisy background. As in other studied biological mechanosensory systems, it is conceivable that the gravisensing process may be amplified by stochastic resonance and nonlinear noise-assisted effects. We therefore investigated the possible dependency of gravisensing on vibrational or thermodynamic noise by examining the effect of external oscillation and temperature on the rate of gravitropic curvature in flax (Linum usitatissimum L.) roots. Roots were oscillated for 15 min prior to or during gravistimulation, either parallel or perpendicular to the root axis. The effect of oscillation was dependent on its direction as well as frequency and amplitude. Initial curvature was most effectively enhanced by vertical oscillations of 5 Hz and 0.5 mm amplitude prior to reorientation. Vertically oscillated roots reached half-maximal curvature 32 min after reorientation, about 18 min earlier than non-oscillated roots. The enhancing effect of vibration on curvature subsided with a half-time of about 20 min. The temperature dependency of the graviresponse indicated that thermodynamic noise also impacted gravity perception. For vibrations and temperature studies, the presentation times decreased almost 6-fold. Our data indicate that gravisensing may depend on or be enhanced by thermodynamic or mechanical noise.

Effects of rhythmic exercise performed to music on the rheological properties of blood in women over 60 years of age.

PubMed

Marchewka, Anna; Filar-Mierzwa, Katarzyna; Dąbrowski, Zbigniew; Teległó, Aneta

2015-01-01

The aim of this study was to analyze the effects of motor rehabilitation, in the form of rhythmic exercise to music, on the rheological characteristics of blood in older women. The study included 30 women (65-80 years of age), and the control group was comprised of 10 women of corresponding age. Women from the experimental group were subjected to a five-month rehabilitation program, in the form of rhythmic exercise performed to music (three 30-minute sessions per week); women from the control group were not involved in any regular physical activity. Blood samples from all the women were examined for hematological, rheological, and biochemical parameters prior to the study and five months thereafter. The rehabilitation program was reflected by a significant improvement of erythrocyte count and hematocrit. Furthermore, an improvement of erythrocyte deformability was observed by lower shear stress levels, while no significant changes were noted by the higher shear stress values. The rehabilitation resulted in a marked decrease of the aggregation amplitude while no significant changes were observed in aggregation index and total aggregation half-time. Additionally, the training regimen was reflected by a significant increase in the plasma viscosity, while no significant changes in fibrinogen levels were noted.

[Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the brain interstitial space].

PubMed

Li, Y Q; Sheng, Y; Liang, L; Zhao, Y; Li, H Y; Bai, N; Wang, T; Yuan, L; Han, H B

2018-04-18

To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd -DO3A-EA-FITC) in brain tissue imaging and brain interstitial space (ISS). In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 μL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups. For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and Gd-DO3A-EA-FITC were as follows: the average diffusion coefficients [(3.31±0.11)×10 -4 mm 2 /s vs. (3.37±0.15)×10 -4 mm 2 /s, t=0.942, P=0.360], the clearance [(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531], the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time [(86.58±3.31) min vs. (84.61±2.38) min, t=1.412, P=0.177], the diffusion areas [(23.25±0.68) mm 2 vs. (22.71±1.00) mm 2 , t=1.100, P=0.297]. The statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant. Moreover, for the optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA-FITC [(22.61±1.16) mm 2 ] was slightly larger than that of FITC [(22.10±1.29) mm 2 ], the statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant (t=0.713, P=0.492). Gd-DO3A-EA-FITC shows the same imaging results as the traditional GD-DTPA, and it can be used in measuring brain ISS.

Models for mesothelioma incidence following exposure to fibers in terms of timing and duration of exposure and the biopersistence of the fibers.

PubMed

Berry, G

1999-02-01

The health effects of inhaled fibers are related to the intensity and duration of exposure and occur many years after the exposure. In particular, the incidence of mesothelioma after exposure to asbestos is proportional to the intensity of exposure (fibers per milliliter of air) and the duration of exposure, and to the time that has elapsed since the exposure. The incidence increases with time since exposure to a power of between 3 and 4. The disease process resulting from exposure to fibers in the air is presumably related to the dose of fibers in the lungs, which depends on the exposure level and duration, and also on the size characteristics of the fibers influencing their inhalation and retention in the lungs. Models incorporating these characteristics have been found to be satisfactory in explaining the incidence of mesothelioma over time after exposure to asbestos. Most of the epidemiological modeling has been for occupational exposure to one of the amphibole asbestos types (crocidolite or amosite), for which heavy exposure produces a high incidence of mesothelioma. Occupational exposure to chrysotile asbestos has resulted in a much lower incidence of mesothelioma. Crocidolite asbestos is much more biopersistent than chrysotile asbestos in the sense that after retention in the lungs it is eliminated only slowly (half-time of several years). If fibers are eliminated then the dose in the lungs declines following exposure, and this may influence the disease process. This concept is more important for synthetic mineral fibers, such as glass wool, which are used as a substitute for asbestos. These fibers are much less biopersistent than asbestos, with half-times of weeks or even days. Biopersistence is related to the dissolution of fibers. This is a physical-chemical process that may be expected to proceed at about the same rate in rats and humans. The predicted effect of biopersistence of fibers has been explored using the basic mesothelioma incidence model generalized to include a term representing exponential elimination over time. The influence of solubility of fibers on the mesothelioma rate is 17 times higher in humans than in rats. This is because rats are aging and developing cancer at a much quicker rate than humans, and hence the influence of dissolution is less. Thus, the predicted mesothelioma incidence in humans is highly dependent on the rate of elimination across the range covering asbestos and the more durable synthetic fibers, but in rats a similar dependence occurs at a 17 times higher rate of elimination corresponding to the less durable synthetic fibers. The possible carcinogenic effects of fibers are often determined from animal experiments, but these results suggest that the extrapolation from rats to humans is highly dependent on the biopersistence of fibers, in the situation where the elimination is through dissolution of fibers at a rate independent of species and the speed of the cancer process is species dependent. This implies that relatively soluble fibers that do not produce disease in rat experiments are even less likely to produce disease in humans.

Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy.

PubMed

Cayir, Derya; Demirel, Koray; Korkmaz, Meliha; Koca, Gokhan

2011-10-01

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T(1/2)) of Tc-99m DTPA were calculated. T(1/2) of whole lung was calculated as a mean of the T(1/2) of left and right lung. The T(1/2) values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86 ± 8.44, and 62.14 ± 26.12 min (p = 0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function.

Supramolecular Polymer Network-Mediated Self-Assembly of Semicrystalline Polymers with Excellent Crystalline Performance.

PubMed

Cheng, Chih-Chia; Chuang, Wei-Tsung; Lee, Duu-Jong; Xin, Zhong; Chiu, Chih-Wei

2017-03-01

A novel application of supramolecular interactions within semicrystalline polymers, capable of self-assembling into supramolecular polymer networks via self-complementary multiple hydrogen-bonded complexes, is demonstrated for efficient construction of highly controlled self-organizing hierarchical structures to offer a direct, efficient nucleation pathway resulting in superior crystallization performance. Herein, a novel functionalized poly(ε-caprolactone) containing self-complementary sextuple hydrogen-bonded uracil-diamidopyridine (U-DPy) moieties is successfully developed and demonstrated excellent thermal and viscoelastic properties as well as high dynamic structural stability in the bulk state due to physical cross-linking created by reversible sextuple hydrogen bonding between U-DPy units. Due to the ability to vary the extent of the reversible network by tuning the U-DPy content, this newly developed material can be readily adjusted to obtain the desired crystalline products with specific characteristics. Importantly, incorporating only 0.1% U-DPy resulted in a polymer with a high crystallization rate constant, short crystallization half-time, and much more rapid crystallization kinetics than pristine PCL, indicating a low content of U-DPy moieties provides highly efficient nucleation sites that manipulate the nucleation and growth processes of polymer crystals to promote crystallization and chain alignment in bulk. This new system is suggested as a potential new route to substantially improve the performance of polymer crystallization. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation, optimization and efficacy evaluation.

PubMed

Dimchevska, Simona; Geskovski, Nikola; Petruševski, Gjorgji; Chacorovska, Marina; Popeski-Dimovski, Riste; Ugarkovic, Sonja; Goracinova, Katerina

2017-03-01

One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol ® F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4 h.

Intraoperative assessment of mitral valve area after mitral valve repair: comparison of different methods.

PubMed

Maslow, Andrew; Gemignani, Anthony; Singh, Arun; Mahmood, Feroze; Poppas, Athena

2011-04-01

In the present study, 3 different methods to measure the mitral valve area (MVA) after mitral valve repair (MVRep) were studied. Data obtained immediately after repair were compared with postoperative data. The objective was to determine the feasibility and correlation between intraoperative and postoperative MVA data. A prospective study. A tertiary care medical center. Twenty-five elective adult surgical patients scheduled for MVRep. Echocardiographic data included MVAs obtained using the pressure half-time (PHT), 2-dimensional planimetry (2D-PLAN), and the continuity equation (CE). These data were obtained immediately after cardiopulmonary bypass and were compared with data obtained before hospital discharge (transthoracic echocardiogram 1) and 6 to 12 months after surgery (transthoracic echocardiogram 2). Intraoperative care was guided by hemodynamic goals designed to optimize cardiac function. The data show good agreement and correlation between MVA obtained with PHT and 2D-PLAN within and between each time period. MVA data obtained with the CE in the postoperative period were lower than and did not correlate or agree as well with other MVA data. The MVA recorded immediately after valve repair, using PHT, correlated and agreed with MVA data obtained in the postoperative period. These results contrast with previously published data and could highlight the impact of hemodynamic function during the assessment of MVA. Copyright © 2011 Elsevier Inc. All rights reserved.

Self-assembly processes in the prebiotic environment

PubMed Central

Deamer, David; Singaram, Sara; Rajamani, Sudha; Kompanichenko, Vladimir; Guggenheim, Stephen

2006-01-01

An important question guiding research on the origin of life concerns the environmental conditions where molecular systems with the properties of life first appeared on the early Earth. An appropriate site would require liquid water, a source of organic compounds, a source of energy to drive polymerization reactions and a process by which the compounds were sufficiently concentrated to undergo physical and chemical interactions. One such site is a geothermal setting, in which organic compounds interact with mineral surfaces to promote self-assembly and polymerization reactions. Here, we report an initial study of two geothermal sites where mixtures of representative organic solutes (amino acids, nucleobases, a fatty acid and glycerol) and phosphate were mixed with high-temperature water in clay-lined pools. Most of the added organics and phosphate were removed from solution with half-times measured in minutes to a few hours. Analysis of the clay, primarily smectite and kaolin, showed that the organics were adsorbed to the mineral surfaces at the acidic pH of the pools, but could subsequently be released in basic solutions. These results help to constrain the range of possible environments for the origin of life. A site conducive to self-assembly of organic solutes would be an aqueous environment relatively low in ionic solutes, at an intermediate temperature range and neutral pH ranges, in which cyclic concentration of the solutes can occur by transient dry intervals. PMID:17008220

Failure of the straight-line DCS boundary when extrapolated to the hypobaric realm.

PubMed

Conkin, J; Van Liew, H D

1992-11-01

The lowest pressure (P2) to which a diver can ascend without developing decompression sickness (DCS) after becoming equilibrated at some higher pressure (P1) is described by a straight line with a negative y-intercept. We tested whether extrapolation of such a line also predicts safe decompression to altitude. We substituted tissue nitrogen pressure (P1N2) calculated for a compartment with a 360-min half-time for P1 values; this allows data from hypobaric exposures to be plotted on a P2 vs. P1N2 graph, even if the subject breathes oxygen before ascent. In literature sources, we found 40 reports of human exposures in hypobaric chambers that fell in the region of a P2 vs. P1N2 plot where the extrapolation from hyperbaric data predicted that the decompression should be free of DCS. Of 4,576 exposures, 785 persons suffered decompression sickness (17%), indicating that extrapolation of the diver line to altitude is not valid. Over the pressure range spanned by human hypobaric exposures and hyperbaric air exposures, the best separation between no DCS and DCS on a P2 vs. P1N2 plot seems to be a curve which approximates a straight line in the hyperbaric region but bends toward the origin in the hypobaric region.

Rising Intracellular Zinc by Membrane Depolarization and Glucose in Insulin-Secreting Clonal HIT-T15 Beta Cells

PubMed Central

Slepchenko, Kira G.; Li, Yang V.

2012-01-01

Zinc (Zn2+) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30–60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells. PMID:22536213

Soups increase satiety through delayed gastric emptying yet increased glycaemic response.

PubMed

Clegg, M E; Ranawana, V; Shafat, A; Henry, C J

2013-01-01

Previous studies have demonstrated the satiating properties of soups compared with solids; however, the mechanisms controlling soup-induced satiety are unknown. This study aimed to understand the physiological mechanisms causing soup to be more satiating. A total of 12 volunteers were tested on three occasions after a solid meal, chunky soup or smooth soup test meal for gastric emptying (GE) using the sodium [1-¹³C] acetate breath test, satiety using visual analog scales (VAS) and glycaemic response (GR) using finger prick blood samples. There was a significant difference in GE half-time (P=0.022) and GE ascension time (P=0.018), with the longest GE times for the smooth soup and the shortest for the solid meal. The GR area under the curve was significantly different between meals (P=0.040). The smooth soup had the greatest GR (87.0 ± 49.5 mmol/l/min), followed by the chunky soup (65.4 ± 48.0 mmol/l/min), with the solid meal having the lowest GR (61.6 ± 36.8 mmol/l/min). Volunteers were fuller after the smooth soup compared with solid meal (P=0.034). The smooth soup induced greater fullness compared with the solid meal because of a combination of delayed GE leading to feelings of gastric distension and rapid accessibility of nutrients causing a greater glycaemic response.

Decrements in knee extensor and flexor strength are associated with performance fatigue during simulated basketball game-play in adolescent, male players.

PubMed

Scanlan, Aaron T; Fox, Jordan L; Borges, Nattai R; Delextrat, Anne; Spiteri, Tania; Dalbo, Vincent J; Stanton, Robert; Kean, Crystal O

2018-04-01

This study quantified lower-limb strength decrements and assessed the relationships between strength decrements and performance fatigue during simulated basketball. Ten adolescent, male basketball players completed a circuit-based, basketball simulation. Sprint and jump performance were assessed during each circuit, with knee flexion and extension peak concentric torques measured at baseline, half-time, and full-time. Decrement scores were calculated for all measures. Mean knee flexor strength decrement was significantly (P < 0.05) related to sprint fatigue in the first half (R = 0.65), with dominant knee flexor strength (R = 0.67) and dominant flexor:extensor strength ratio (R = 0.77) decrement significantly (P < 0.05) associated with sprint decrement across the entire game. Mean knee extensor strength (R = 0.71), dominant knee flexor strength (R = 0.80), non-dominant knee flexor strength (R = 0.75), mean knee flexor strength (R = 0.81), non-dominant flexor:extensor strength ratio (R = 0.71), and mean flexor:extensor strength ratio (R = 0.70) decrement measures significantly (P < 0.05) influenced jump fatigue during the entire game. Lower-limb strength decrements may exert an important influence on performance fatigue during basketball activity in adolescent, male players. Consequently, training plans should aim to mitigate lower-limb fatigue to optimise sprint and jump performance during game-play.

Annual report of the United States transuranium and uranium registries, October 1, 1988--September 30, 1989

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathren, R.L.; Swint, M.J.; Dietert, S.E.

1990-04-01

This report summarizes the primary scientific activities of the United States Transuranium and Uranium Registries for the period October 1, 1988 through September 30, 1989. The Registries are parallel human tissue research programs devoted to the study of the actinide elements in man. The emphasis of the Transuranium Registry was directed toward evaluation of six whole body donations. In the five cases whose exposure was through inhalation, approximately half of the total body content of Pu-239 + 240 and a third of the Am-241 was found in the respiratory tract, suggesting that these nuclides are more avidly retained than predictedmore » by the current model of the International Commission on Radiological Protection. A significant fraction of these nuclides is found in soft tissues other than liver, and an uptake fraction of 0.2 is proposed for muscle, with a residence half-time of 10 years. Studies of these and routine autopsy cases indicate that more than 90% of the total respiratory tract plutonium or americium is in the lungs, with the remainder in the lymph nodes, and that a greater fraction is found in the lungs of smokers relative to the lymph nodes. Primary activities of the Uranium Registry centered around the acquisition of a whole body donation from a woman who had received an injection of colloidal thorium dioxide some 38 years prior to death.« less

Impact of Official Matches on Soccer Referees' Power Performance.

PubMed

Castillo, Daniel; Yanci, Javier; Cámara, Jesús

2018-03-01

The evaluation of match officials' neuromuscular performance is now an important consideration and the vertical jump test is considered suitable for assessing lower limb power, partly because it is directly related to refereeing. The aim of this study, therefore, was to determine the effect of soccer matches on match officials' vertical jump performance by assessing various biomechanical variables. Eighteen field referees (FRs) and 36 assistant referees (ARs) who officiated in 18 official matches participated in this study. Before the match, at half time and immediately after the match, officials performed two countermovement jumps. Flight phase time (FT), maximum force production (MFpropulsion), time to production of maximum force (TMFpropulsion), production of maximum power (MP), maximum landing force (MFlanding) and time to stabilization (TTS) were calculated for all jumps. There was a tendency for match officials' jumping performance to improve after matches than beforehand (FR: effect size (ES) = 0.19 ± 0.36, possibly trivial; AR: ES = 0.07 ± 0.17, likely trivial). There were also likely small and very likely moderate differences between FRs' MP in pre-match and half-time jumps (ES = 0.46 ± 0.47) and in their pre- and post-match jumps (ES = 0.71 ± 0.48). These results indicate that refereeing soccer matches does not reduce vertical jump performance; the subsequent neuromuscular fatigue is not sufficient to affect landing technique.

Metabolism and excretion of 2-ethoxyethanol in the adult male rat.

PubMed Central

Cheever, K L; Plotnick, H B; Richards, D E; Weigel, W W

1984-01-01

The routes of 14C excretion following the administration of a single oral 230 mg/kg body weight dose of 2-ethoxyethanol [ethanol-1,2-14C] or 2-ethoxyethanol [ethoxy-1-14C] to male Sprague-Dawley rats were investigated. Elimination of the 14C by the urinary route accounted for 76 to 80% of the dose within 96 hr. The main pathway of biotransformation is oxidation to the corresponding acid, with some subsequent conjugation of the acid metabolite with glycine. The major metabolites, ethoxyacetic acid and N-ethoxy-acetyl glycine, representing 73 to 76% of the administered dose, were eliminated in the urine. The major difference in the metabolic profiles of the two radiochemicals was in the rate and amount of 14CO2 expired via the lung. Of the administered 14C, 11.7% of the ethoxy-labeled and 4.6% of the ethanol-labeled compounds were eliminated as CO2. The biological half-time was 9.9 +/- 1.5 hr for the ethoxy-labeled compound and 12.5 +/- 1.9 hr for the ethanol label. After administration of the ethanol-labeled compound, the only radiolabeled component found in the rat testes was identified as ethoxyacetic acid. Results of this study suggest that the reported testicular effects in the rat may be a result of tissue levels of ethoxyacetic acid. PMID:6437805

A spectral analysis of team dynamics and tactics in Brazilian football.

PubMed

Moura, Felipe Arruda; Martins, Luiz Eduardo Barreto; Anido, Ricardo O; Ruffino, Paulo Régis C; Barros, Ricardo M L; Cunha, Sergio Augusto

2013-01-01

The purposes of this study were to characterise the total space covered and the distances between players within teams over ten Brazilian First Division Championship matches. Filmed recordings, combined with a tracking system, were used to obtain the trajectories of the players (n = 277), before and after half-time. The team surface area (the area of the convex hull formed by the positions of the players) and spread (the Frobenius norm of the distance-between-player matrix) were calculated as functions of time. A Fast Fourier Transform (FFT) was applied to each time series. The median frequency was then calculated. The results of the surface area time series median frequencies for the first half (0.63 ± 0.10 cycles · min⁻¹) were significantly greater (P < 0.01) than the second-half values (0.47 ± 0.14 cycles · min⁻¹). Similarly, the spread variable median frequencies for the first half (0.60 ± 0.14 cycles · min⁻¹) were significantly greater (P < 0.01) than the second-half values (0.46 ± 0.16 cycles · min⁻¹). The median frequencies allowed the characterisation of the time series oscillations that represent the speed at which players distribute and then compact their team formation during a match. This analysis can provide insights that allow coaches to better control the team organisation on the pitch.

Dissipation of the Proton Electrochemical Potential in Intact and Lysed Chloroplasts 1

PubMed Central

Nishio, John N.; Whitmarsh, John

1991-01-01

Effective ionophore:chlorophyll ratios were determined for various ionophores that decrease the electrical potential across thylakoid membranes in intact and hypo-osmotically lysed chloroplasts isolated from spinach (Spinacia oleracea). The efficacy of gramicidin D, valinomycin, carbonylcyanide m-chlorophenylhydrazone, and dicyclohexano-18-crown-6 in collapsing the electrical potential was determined spectrophotometrically by the decay half-time of the absorbance change at 518 nanometers induced by a saturating, single turnover flash. The results show that the effectiveness of the ionophores in collapsing the electrical potential in intact and lysed chloroplasts depends on the amount of ionophore-accessible membrane in the assay medium. Only gramicidin exhibited a significant difference in efficacy between intact and lysed chloroplasts. The ratio of gramicidin to chlorophyll required to collapse the electrical potential was more than 50 times higher in intact chloroplasts than in lysed chloroplasts. The efficacy of carbonylcyanide m-chlorophenylhydrazone was significantly reduced in the presence of bovine serum albumin. The other ionophores tested maintained their potency in the presence of bovine serum albumin. Valinomycin was the most effective ionophore tested for collapsing the electrical potential in intact chloroplasts, whereas gramicidin was the most potent ionophore in lysed chloroplasts. The significance of the ionophore:chlorophyll ratios required to collapse the electrical potential is discussed with regard to bioenergetic studies, especially those that examine the contribution of the transmembrane electrochemical potential to protein transport into chloroplasts. PMID:16668015

Thermal and tensile properties of alumina filled PET nanocomposites

NASA Astrophysics Data System (ADS)

Nikam, Pravin N.; Deshpande, Vineeta D.

2018-05-01

In the present investigation, nanocomposites of poly(ethylene terephathalate)(PET) with different content (0 to 5 wt.%) of alumina nanoparticles (n-Al2O3) were prepared by melt-extrusion technique. Morphological characterization of samples was examined by transmission electron microscopy (TEM). Morphological analysis revealed that degree of dispersion of alumina nanoparticles (ANPs) was increased at lower content (i.e. upto 2 wt.%), which observed by TEM. Thermal and tensile measurements were carried out using and differential scanning calorimetry (DSC) and universal testing machine (UTM). The thermal analysis showed that the glass transition termperature (Tg), melting temperature (Tm), crystallization temperature (Tc) of PET/alumina nanocomposites (PNCs) were higher than neat PET (PET0). The heat enthalpy (ΔHm) of crystallization for PNCs was increased compared to PET0, which indicates that degree of crystallinity of PNCs also increased compared to PET0. The half-time (t0.5) of crystallization of PNCs were decreased compared to PET0 which indicates that the incorporation of ANPs nucleate the PET molecular chains and allowing the easily crystallization during nonisothermal process. The tensile analysis revealed that the tensile elastic modulus (i.e. Young's modulus) of PNCs increased almost linearly with increasing the content of ANPs while tensile elongation at break decreased nonlinearly. The tensile strength of PNCs increased with a 1 wt.% of ANPs whereas the higher content of ANPs decreased the tensile strength.

Brain synaptosomes display a diadenosine tetraphosphate (Ap4A)-mediated Ca2+ influx distinct from ATP-mediated influx.

PubMed

Pivorun, E B; Nordone, A

1996-06-01

Studies undertaken to compare the effects of Ap4A and ATP on altering intrasynaptosomal Ca2+ levels from deermouse brain reveal that both ligands induce a rapid influx of extracellular Ca2+. The Ca2+ profile elicited by 167 microM Ap4A is "spike-like" (half-time for decline to baseline, 19.1 +/- 1.2 sec), in contrast to the gradual decline observed with ATP (104.0 +/- 7.4 sec). DIDS (4-4'-diisothiocyano-2,2'-disulfonic acid stilbene) and suramin preincubation alter only the ATP-induced Ca2+ profile. Cross-desensitization studies indicate that prior application of ATP does not significantly affect the Ca2+ influx elicited by Ap4A, and that prior application of Ap4A does not affect the Ca2+ influx elicited by ATP. These results demonstrate that extracellular Ap4A and ATP elicit distinct intrasynaptosomal Ca2+ influx profiles, and suggest that these two nucleotides may be interacting with distinct purinoceptor subclasses or purinoceptor-effector complexes. Subjecting the synaptosomes simultaneously to depolarization and Ap4A, or to depolarization and ATP, induces an additive effect on Ca2+ influx. Preincubation with verapamil negates the effects of depolarization without modifying the ligand-elicited Ca2+ fluxes. These results indicate the presence of Ap4A and ATP ligand-gated channels that may function as modulators of neuronal activity.

European EVA decompression sickness risks

NASA Astrophysics Data System (ADS)

Vogt, Lorenz; Wenzel, Jürgen; Skoog, A. I.; Luck, S.; Svensson, Bengt

For the first manned flight of Hermes there will be a capability of performing EVA. The European EVA Space Suit will be an anthropomorphic system with an internal pressure of 500 hPa of pure oxygen. The pressure reduction from the Hermes cabin pressure of 1013 hPa will induce a risk for Decompression Sickness (DCS) for the EVA crewmember if no adequate protective procedures are implemented. Specific decompression procedures have to be developed. From a critical review of the literature and by using knowledge gained from research conducted in the past in the fields of diving and aerospace medicine safe protective procedures are proposed for the European EVA scenario. An R factor of 1.2 and a tissue half-time ( t1/2) of 360 minutes in a single-tissue model have been identified as appropriate operational values. On the basis of an acceptable risk level of approximately 1%, oxygen prebreathing times are proposed for (a) direct pressure reduction from 1013 hPa to a suit pressure of 500 hPa, and (b) staged decompression using a 700 hPa intermediate stage in the spacecraft cabin. In addition, factors which influence individual susceptibility to DCS are identified. Recommendations are also given in the areas of crew selection and medical monitoring requirements together with therapeutic measures that can be implemented in the Hermes scenario. A method for demonstration of the validity of proposed risks and procedures is proposed.

Sphingomyelinase-Induced Domain Shape Relaxation Driven by Out-of-Equilibrium Changes of Composition

PubMed Central

Fanani, Maria Laura; De Tullio, Luisina; Hartel, Steffen; Jara, Jorge; Maggio, Bruno

2009-01-01

Abstract Sphingomyelinase (SMase)-induced ceramide (Cer)-enriched domains in a lipid monolayer are shown to result from an out-of-equilibrium situation. This is induced by a change of composition caused by the enzymatic production of Cer in a sphingomyelin (SM) monolayer that leads to a fast SM/Cer demixing into a liquid-condensed (LC), Cer-enriched and a liquid-expanded, SM-enriched phases. The morphological evolution and kinetic dependence of Cer-enriched domains is studied under continuous observation by epifluorescence microscopy. Domain shape annealing is observed from branched to rounded shapes after SMase activity quenching by EDTA, with a decay halftime of ∼10 min. An out-of-equilibrium fast domain growth is not the determinant factor for domain morphology. Domain shape rearrangement in nearly equilibrium conditions result from the counteraction of intradomain dipolar repulsion and line tension, according to McConnell's shape transition theory. Phase separation causes a transient compositional overshoot within the LC phase that implies an increased out-of-equilibrium enrichment of Cer into the LC domains. As a consequence, higher intradomain repulsion leads to transient branched structures that relax to rounded shapes by lowering the proportion of Cer in the domain to equilibrium values. The fast action of SMase can be taken as a compositional perturbation that brings about important consequences for the surface organization. PMID:18849413

Dynamic Postural-Stability Deficits After Cryotherapy to the Ankle Joint.

PubMed

Fullam, Karl; Caulfield, Brian; Coughlan, Garrett F; McGroarty, Mark; Delahunt, Eamonn

2015-09-01

Decreased postural stability is a primary risk factor for lower limb musculoskeletal injuries. During athletic competitions, cryotherapy may be applied during short breaks in play or during half-time; however, its effects on postural stability remain unclear. To investigate the acute effects of a 15-minute ankle-joint cryotherapy application on dynamic postural stability. Controlled laboratory study. University biomechanics laboratory. A total of 29 elite-level collegiate male field-sport athletes (age = 20.8 ± 1.12 years, height = 1.80 ± 0.06 m, mass = 81.89 ± 8.59 kg) participated. Participants were tested on the anterior (ANT), posterolateral (PL), and posteromedial (PM) reach directions of the Star Excursion Balance Test before and after a 15-minute ankle-joint cryotherapy application. Normalized reach distances; sagittal-plane kinematics of the hip, knee, and ankle joints; and associated mean velocity of the center-of-pressure path during performance of the ANT, PL, and PM reach directions of the Star Excursion Balance Test. We observed a decrease in reach-distance scores for the ANT, PL, and PM reach directions from precryotherapy to postcryotherapy (P < .05). No differences were observed in hip-, knee-, or ankle-joint sagittal-plane kinematics (P > .05). We noted a decrease in mean velocity of the center-of-pressure path from precryotherapy to postcryotherapy (P < .05) in all reach directions. Dynamic postural stability was adversely affected immediately after cryotherapy to the ankle joint.

The United States Transuranium and Uranium Registries. Revision 1, [Annual] report, October 1, 1990--April 1992

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathren, R.L.

1992-09-01

This paper describes the history, organization, activities and recent scientific accomplishments of the United States Transuranium and Uranium Registries. Through voluntary donations of tissue obtained at autopsies, the Registries carry out studies of the concentration, distribution and biokinetics of plutonium in occupationally exposed persons. Findings from tissue analyses from more than 200 autopsies include the following: a greater proportion of the americium intake, as compared with plutonium, was found in the skeleton; the half-time of americium in liver is significantly shorter than that of plutonium; the concentration of actinide in the skeleton is inversely proportional to the calcium and ashmore » content of the bone; only a small percentage of the total skeletal deposition of plutonium is found in the marrow, implying a smaller risk from irradiation of the marrow relative to the bone surfaces; estimates of plutonium body burden made from urinalysis typically exceed those made from autopsy data; pathologists were unable to discriminate between a group of uranium workers and persons without known occupational exposure on the basis of evaluation of microscopic kidney slides; the skeleton is an important long term depot for uranium, and that the fractional uptake by both skeleton and kidney may be greater than indicated by current models. These and other findings and current studies are discussed in depth.« less

Dosimetry of radium-223 and progeny

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, D.R.; Sgouros, G.

Radium-223 is a short-lived (11.4 d) alpha emitter with potential applications in radioimmunotherapy of cancer. Radium-223 can be complexed and linked to protein delivery molecules for specific tumor-cell targeting. It decays through a cascade of short-lived alpha- and beta-emitting daughters with emission of about 28 MeV of energy through complete decay. The first three alpha particles are essentially instantaneous. Photons associated with Ra-223 and progeny provide the means for tumor and normal-organ imaging and dosimetry. Two beta particles provide additional therapeutic value. Radium-223 may be produced economically and in sufficient amounts for widescale application. Many aspects of the chemistry ofmore » carrier-free isotope preparation, complexation, and linkage to the antibody have been developed and are being tested. The radiation dosimetry of a Ra-223-labeled antibody shows favorable tumor to normal tissue dose ratios for therapy. The 11.4-d half-life of Ra-223 allows sufficient time for immunoconjugate preparation, administration, and tumor localization by carrier antibodies before significant radiological decay takes place. If 0.01 percent of a 37 MBq (1 mCi) injection deposits in a one gram tumor mass, and if the activity is retained with a typical effective half-time (75 h), the absorbed dose will be 163 mGy MBq{sup {minus}1} (600 rad mCi{sup {minus}1}) administered. 49 refs., 5 figs., 2 tabs.« less

High affinity soluble ILT2 receptor: a potent inhibitor of CD8(+) T cell activation.

PubMed

Moysey, Ruth K; Li, Yi; Paston, Samantha J; Baston, Emma E; Sami, Malkit S; Cameron, Brian J; Gavarret, Jessie; Todorov, Penio; Vuidepot, Annelise; Dunn, Steven M; Pumphrey, Nicholas J; Adams, Katherine J; Yuan, Fang; Dennis, Rebecca E; Sutton, Deborah H; Johnson, Andy D; Brewer, Joanna E; Ashfield, Rebecca; Lissin, Nikolai M; Jakobsen, Bent K

2010-12-01

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms: LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.

Dynamic alteration in splenic function during acute falciparum malaria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Looareesuwan, S.; Ho, M.; Wattanagoon, Y.

Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated /sup 51/Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes (mean +/- SD) vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than didmore » the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.« less

Hyperventilation with and without maintenance of isocapnia: a comparison of selected gasometric and respiratory parameters.

PubMed

Sein Anand, Jacek; Wiśniewski, Marek; Waldman, Wojciech

2014-09-15

The aims of this study were to examine selected respiratory and gasometric parameters during hyperventilation with and without isocapnia and to identify the possible mechanism by which isocapnic hyperventilation might be useful in the elimination of volatile substances, including CO. Ten healthy non-smoking volunteers were studied, and each underwent two procedures. During one session, CO2 was added to the respiratory circuit, and during the other session, only 100% O2 was used. The volunteers were coached to hyperventilate until the appearance of side effects. Isocapnic hyperventilation significantly increased alveolar minute ventilation and partial pressure of oxygen in arterialized capillary blood (paO2); to the best of our knowledge, these findings have not previously been reported. Isocapnic hyperventilation was associated with only mild side effects, such as dyspnea, increased respiratory effort and headache, in 30% of subjects. Side effects, including vertigo, paresthesias and muscle tremor, were present in 70% of the volunteers during hyperventilation with 100% O2, and these side effects forced them to limit their respiratory rates and tidal volumes. These increases in alveolar ventilation and the partial pressure of oxygen in the blood may play crucial roles in decreasing the half-time of carboxyhemoglobin, which is the primary goal of the treatment of CO poisoning. Copyright © 2014 Elsevier B.V. All rights reserved.

Detoxification of tabun at physiological pH mediated by substituted β-cyclodextrin and glucose derivatives containing oxime groups.

PubMed

Brandhuber, Florian; Zengerle, Michael; Porwol, Luzian; Tenberken, Oliver; Thiermann, Horst; Worek, Franz; Kubik, Stefan; Reiter, Georg

2012-12-16

The ability of 13 β-cyclodextrin and 2 glucose derivatives containing substituents with oxime groups as nucleophilic components to accelerate the degradation of tabun at physiological pH has been evaluated. To this end, a qualitative and a quantitative enzymatic assay as well as a highly sensitive enantioselective GC-MS assay were used. In addition, an assay was developed that provided information about the mode of action of the investigated compounds. The results show that attachment of pyridinium-derived substituents with an aldoxime group in 3- or 4-position to a β-cyclodextrin ring affords active compounds mediating tabun degradation. Activities differ depending on the structure, the number, and the position of the substituent on the ring. Highest activity was observed for a β-cyclodextrin containing a 4-formylpyridinium oxime residue in 6-position of one glucose subunit, which detoxifies tabun with a half-time of 10.2 min. Comparison of the activity of this compound with that of an analog in which the cyclodextrin ring was replaced by a glucose residue demonstrated that the cyclodextrin is not necessary for activity but certainly beneficial. Finally, the results provide evidence that the mode of action of the cyclodextrin involves covalent modification of its oxime group rendering the scavenger inactive after reaction with the first tabun molecule. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Desensitization of atriopeptin stimulated accumulation and extrusion of cyclic GMP from a kidney epithelial cell line (MDCK).

PubMed

Woods, M; Houslay, M D

1991-02-01

Atriopeptin caused dose- (EC50 ca. 2 x 10(-8) M) and time-dependent increases in the intracellular concentration of cyclic GMP in the MDCK kidney epithelial cell line; an effect potentiated by the phosphodiesterase inhibitor, IBMX. The atriopeptin-catalysed increase in cyclic GMP was transient and reached a maximum some 10-20 min after challenge of cells with atriopeptin. The basis for the transience of this increase was shown to be due to the desensitization of guanylate cyclase coupled with extrusion of cyclic GMP from the cells and the degradation of cyclic GMP by phosphodiesterase activity. Atriopeptin-catalysed extrusion of cyclic GMP was time- and dose-(EC50 ca. 1.5 x 10(-8) M) dependent and was inhibited by probenecid but not by high external cyclic GMP concentrations. The extrusion process underwent apparent desensitization as did guanylate cyclase with similar half lives (T1/2 of ca. 20 min). Desensitization was dose-dependent upon atriopeptin and did not appear to be mediated by elevated cyclic GMP concentrations as pre-incubation with 8-bromo cyclic GMP did not cause desensitization and the half-times for desensitization were similar whether or not IBMX was present. The majority of the cyclic nucleotide phosphodiesterase activity was found in the cytosol fraction of the cells and could be separated into two cyclic AMP specific forms and two cyclic GMP preferring forms.

Geochemistry and microbiology of iron-related well-screen encrustation and aquifer biofouling in Suffolk County, Long Island, New York

USGS Publications Warehouse

Walter, D.A.

1997-01-01

Iron-related well-screen encrustation and aquifer biofouling has decreased the specific capacity of several production wells in Suffolk County, N.Y., and has forced the Suffolk County Water Authority to adopt a costly well-reconditioning and replacement program. The specific-capacity declines are the result of the precipitation of iron oxyhydroxides and the growth of iron bacteria on the well screens and in the pore spaces of the surrounding formation. Mineralogic and chemical analyses indicate that the inorganic part of the encrusting material consists primarily of amorphous ferric hydroxide (Fe(OH)3 ); minor components of the material include goethite (FeOOH), hematite (Fe2 O 3 ), and quartz (SiO 2 ). The weight percent of ferric hydroxide in the material ranged from 32.3 to 98.6 percent and averaged 64.3 percent. Equilibrium modeling indicated that during pumping the well waters were supersaturated with respect to goethite, hematite, magnetite, and quartz and were under-saturated with respect to ferric hydroxide. Theoretical Eh values computed for the ferrous/ferric-iron redox couple and the oxygen/water redox couple averaged 390 millivolts and 810 millivolts, respectively, indicating that the waters were in a state of redox disequilibrium. The disequilibrium condition arises from the mixing of ground water with a low dissolved-oxygen concentration with oxygenated ground water during operation of the well. The low pH of the ground water contributes to the disequilibrium condition by slowing the rate of iron oxidation after the introduction of oxygen. Chemical and mineralogical data indicate that most of the encrusting material in the wells was deposited while the wells were shut down, probably in response to the use of treated water of higher pH to keep pump turbines wet while the wells were not in operation; the increased pH of water in the static water column increases the rate of ferrous-iron oxidation and causes the well water to become increasingly saturated with respect to ferric hydroxide. The median half-time of oxidation in samples of untreated ground water (pH 4-5) was 4.19 days, whereas the average half-time of oxidation in treated water (pH 7-8) was 11.9 minutes Equilibrium modeling indicated that treated waters generally were supersaturated with respect to ferric hydroxide, whereas untreated well waters were not. Field and laboratory data indicate that iron bacteria play an important role in the encrustation and biofouling process in Suffolk County. Filamentous iron bacteria were common in the affected wells. The most common species was Gallionella ferruginea, an effective biofouling agent that prefers water with low, but detectable, dissolved-oxygen concentrations and high dissolved-iron concentrations; this species was more common in biofilm samples from the Magothy aquifer than in those from the upper glacial aquifer. Iron bacteria also were found in sediment cores from several locations in the aquifer and in drilling water. Lignite could act as a carbon source for heterotrophic iron bacteria, which could accelerate the formation of iron-bacteria biofilms in wells screened in some parts of the Magothy aquifer. Iron-bacteria biofilms alter the chemistry of well water by removing iron, manganese, and sulfate from solution and by increasing the pH. Sulfur-reducing bacteria and iron-sulfide mineral phases were observed in some samples of encrusting material, indicating that these bacteria could contribute to well-screen encrustation in some geochemical environments.

MTBE inhaled alone and in combination with gasoline vapor: uptake, distribution, metabolism, and excretion in rats.

PubMed

Benson, J M; Barr, E B; Krone, J R

2001-05-01

The purpose of these studies was to extend previous evaluation of methyl tert-butyl ether (MTBE)* tissue distribution, metabolism, and excretion in rats to include concentrations more relevant to human exposure (4 and 40 ppm) and to determine the effects of coinhalation of the volatile fraction of unleaded gasoline on the tissue distribution, metabolism, and excretion of MTBE. Groups of male F344 rats were exposed nose-only for 4 hours to 4, 40, or 400 ppm 14C-MTBE or to 20 or 200 ppm of the light fraction of unleaded gasoline (LFG) containing 4 or 40 ppm 14C-MTBE, respectively. To evaluate the effects of repeated inhalation of LFG on MTBE tissue distribution, metabolism, and excretion, rats were exposed for 4 hours on each of 7 consecutive days to 20 or 200 ppm LFG with MTBE (4 or 40 ppm) followed on the eighth day by a similar exposure to LFG containing 14C-MTBE. Subgroups of rats were evaluated for respiratory parameters, initial body burdens, rates and routes of excretion, and tissue distribution and elimination. The concentrations of MTBE and its chief metabolite, tert-butyl alcohol (TBA), were measured in blood and kidney immediately after exposure, and the major urinary metabolites-2-hydroxyisobutyric acid (IBA) and 2-methyl-1,2-propanediol (2MePD)-were measured in urine. Inhalation of MTBE alone or as a component of LFG had no concentration-dependent effect on respiratory minute volume. The initial body burdens of MTBE equivalents achieved after 4 hours of exposure to MTBE did not increase linearly with exposure concentration. MTBE equivalents rapidly distributed to all tissues examined, with the largest percentages distributed to liver. The observed initial body burden did not increase linearly between 4 and 400 ppm. At 400 ppm, elimination half-times of MTBE equivalents from liver increased and from lung, kidney, and testes decreased compared with the two smaller doses. Furthermore, at 400 ppm the elimination half-time for volatile organic compounds (VOCs) in breath was significantly shorter and the percentage of the initial body burden of MTBE equivalents eliminated as VOCs in breath increased significantly. These changes probably reflect a saturation of blood with MTBE at 400 ppm and strongly suggest that the uptake and fate of MTBE are notably different at exposure concentrations above and below 400 ppm. Single and repeated coexposure to 20 and 200 ppm LFG with MTBE had opposite effects on the total body burden of MTBE equivalents present at the end of exposures compared with those achieved after 4 and 40 ppm MTBE exposures: 20 ppm LFG increased and 200 ppm LFG significantly decreased the burdens of MTBE equivalents present. The effects of coexposure to LFG on blood levels of MTBE equivalents paralleled the effects on body burden. These differences in overall uptake of MTBE equivalents cannot be attributed to alterations of minute volume. The reason for the increase in overall uptake after 20-ppm LFG exposure is not clear. Decreased MTBE absorption (uptake) after single and repeated coexposure to 200 ppm LFG may be due to a decrease in solubility of MTBE in blood caused by inhalation of other hydrocarbons. Investigations on the blood/air partition coefficient of MTBE in the absence and presence of LFG would be needed to confirm this hypothesis. Single and repeated coexposure to either 20 or 200 ppm LFG significantly decreased the percentage of the initial body burden from MTBE equivalents in tissues, including liver, kidney, and testes, immediately and 72 hours after

[Effect of acute biliary pancreatitis on liver metabolism of phenazone].

PubMed

Hartleb, M; Nowak, A; Nowakowska-Duława, E; Mańczyk, I; Becker, A; Kacperek, T

1990-03-01

In 22 patients with acute pancreatitis caused by biliary calculi and 9 healthy controls the rate of hepatic elimination of phenazone was measured. The aim of the study was evaluation of the oxidative-detoxicating action of the liver in this disease in relation to its severity. In pancreatitis patients the half-time (T2) of phenazone was significantly (p less than 0.01 longer than in healthy subjects (23.6 +/- 10.5 vs 13.2 +/- 7.2 hrs). The T2 of phenazone was not correlated with the concentrations of transaminases, bilirubin and prothrombin, but was correlated positively with the concentration of hepatic lactic dehydrogenase (p less than 0.001). In the initial stage of pancreatitis the T2 of phenazone was without prognostic significance and showed no agreement with Ranson's clinical-laboratory classification of the severity of the disease. The degree of impairment of the hepatic metabolism of phenazone measured with the percent difference between T2 of phenazone in both tests was significantly (p less than 0.05) greater in the group of patients with complications than in those without pancreatitis complications (70.7 +/- 64.4% vs 21.4 +/- 16.2%). Biliary pancreatitis impairs the oxidative-reductive function of the liver proportionally to the degree of hepatic lactic dehydrogenase in the serum. Evaluation of the rate of hepatic elimination of phenazone in the initial stage of this pancreatitis was without prognostic importance for the severity of the disease.

The effect of agar jelly on energy expenditure, appetite, gastric emptying and glycaemic response.

PubMed

Clegg, Miriam E; Shafat, Amir

2014-01-01

Agar contains a high amount of soluble fibre and has been shown to delay gastric emptying (GE) without impacting on glycaemic response (GR). The current study aimed to further the limited data on the effect of agar on metabolism by assessing the effects on GE and GR as well as appetite- and diet-induced thermogenesis (DIT). In this randomized control trial, eleven healthy volunteers were tested on two occasions following an overnight fast. Following baseline and resting measurements, volunteers were either fed a fruit-flavoured drink (liquid) or consumed a fruit-flavoured jelly (jelly). The two were exactly the same in composition except the jelly contained 4 g of agar crystals. Both contained 50 g of available carbohydrate. DIT was measured using indirect calorimetry, GE using the (13)C sodium acetate breath test, appetite using visual analogue scale and GR using finger prick blood samples. The jelly significantly delayed GE across all time points-latency phase (p = 0.07), lag phase (p = 0.04), half-time (p < 0.0001), ascension time (p = 0.025). The jelly also increased all appetite parameters-hunger (p = 0.006), fullness (p = 0.035), desire to eat (p = 0.03) and prospective consumption (p = 0.011). However, there were no significant differences in either GR or postprandial DIT between the liquid and jelly. Agar delays GE and increases appetite but does not change GR or DIT most probably due to the increase in viscosity caused by the agar jelly.

$sup 137$CCs and $sup 40$K in the flesh of Pacific albacore, 1964--1974

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, D.R.; Folsom, T.R.; Hodge, V.F.

1975-11-01

Concentrations of $sup 137$Cs in the flesh of albacore tuna caught off the California coast during the last 10 yr decreased by a considerably smaller factor than did corresponding values reported for atmospheric fallout. Between 1965 and 1974, average tissue concentrations decreased steadily from 90 to approx 40 pCi/wet kg, which suggests an effective half-time for $sup 137$Cs in the upper layer of the eastern North Pacific of about 1 decade. Values for natural $sup 40$K, which was measured at the same time, averaged 3300 pCi/wet kg. The 1965 mean concentrations of $sup 137$Cs in albacore from four widely separatedmore » fisheries in the Northern Hemisphere agreed within a factor of two, ranging from 50 to 90 pCi/wet kg. In contrast, specimens from South Pacific fishery based at American Samoa averaged only 14 pCi/wet kg. Surface seawater collected around Tutuila Island averaged 0.085 pCi/l. $sup 137$Cs, in good agreement with measurements made a year later over a much wider area of the South Pacific. No large variations in flesh concentrations of $sup 137$Cs or $sup 40$K were observed as a function of tuna size, species, portion of the body sampled, or cooking. Thus, radioanalysis of canned tuna may be an efficient method of following major changes in $sup 137$Cs contamination of upper layers of the world ocean. (auth)« less

Design of YCF-1 mobile γ irradiator

NASA Astrophysics Data System (ADS)

Hehu, Zhang; Chuanzhen, Wang

1993-07-01

YCF-1 Mobile irradiator is designed by BINE of China. It has been put into running in YanJi city of Jilin province. It is able to be moved to border and distance places and area lumped and spreading out of agricultural products to service. It can play a important role in demonstration and extending irradiation technology in food irradiation, disinfestation, sterilization and quarantine, etc. This paper describes the features and design considerations of mobile irradiator. This irradiator adopted Cesium-137 source. The design capacity of loading source is 9.25PBq (250kCi), A half-time of Cs- 137 is 30.2 years long, exchanging source is not needed utilization rate of energy is higher, and the shielding is thinner, The Weight is lighter, The dose rate on the surface of it is 0.0025mSv/h in accordance with national standard. The internal size of irradiation room is 1800×1800×900mm (L×W×H), The sheilding of irradiation room is a steel shell filled with lead. The thickness of lead is 18cm. The irradiator is installed on a special flat truck. The size of the truck is 7000×3400×4200mm (L×W×H). The weight of irradiator is more than 80 150kw. The main components and parts of irradiator are: source, source racks and hoist, irradiation chamber, storage source chamber, the product's transport system, dose monitoring system, ventilation system and safety interlock system, etc.

PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody fab fragment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Page, R.L.; Garg, P.K.; Gard, S.

Four dogs with histologically confirmed osteogenic sarcoma were studied with PET following intravenous injection of the {sup 18}F-labeled Fab fragment of TP-3, a monoclonal antibody specific for human and canine osteosarcomas. The antibody fragment was labeled using the N-succinimidyl (8-(4{prime}-({sup 18}F)fluorobenzyl)amino)suberate acylation agent. Blood clearance of activity was biphasic in all dogs but half-times were variable (T{sub 1/2{beta}} = 2-13 hr). Catabolism of labeled Fab was reflected by the decrease in protein-associated activity in serum from more than 90% at 1 min to 60%-80% at 4 hr. PET images demonstrated increased accumulation of {sup 18}F at the primary tumor sitemore » relative to normal contralateral bone in one dog as early as 15 min after injection. Biopsies obtained after euthanasia indicated higher uptake at the edges of the tumor as observed on the PET scans. Tumor uptake was 1-3 x 10{sup -3}% injected dose/g, a level similar to that reported for other Fab fragments in human tumors. In the three dogs with metastatic disease, early PET images reflected activity in the blood pool but later uptake was observed in suspected metastatic sites. These results, although preliminary, suggest that PET imaging of {sup 18}F-labeled antibody fragments is feasible and that dogs with spontaneous tumors could be a valuable model for preclinical research with radioimmunoconjugates. 34 refs., 6 figs., 2 tabs.« less

[Burnout syndrome in teachers from two universities in Popayán, Colombia].

PubMed

Correa-Correa, Zamanda; Muñoz-Zambrano, Isabel; Chaparro, Andrés F

2010-08-01

Evaluating professional exhaustion or burnout syndrome: background, syndrome and consequences amongst half-time and full-time staff working in two private universities in the city of Popayán during 2008. The study population included 44 male and female participants aged 20 to 40 who were evaluated by using a brief burnout questionnaire (BBQ). This questionnaire had been validated for Latin-American and for teachers. It was not exclusively focused on the structure of the syndrome itself but rather included background elements and consequences. The study was quantitative and cross-sectional, having a deductive hypothetical methodological focus. Descriptive statistics and the Chi-square test were used for data analysis, accepting p<0.05 statistical significance. The analysis was univariate and bivariate. The results indicated low burnout syndrome frequency in the study population. However, 9.1 % high depersonalization frequency was found (i.e. teachers had developed negative attitudes and were insensitive to those receiving their services) and 15.9 % and 9.1 % frequencies for high physical and social consequences, respectively. Bivariate analysis revealed significant association of several factors. The results indicated low burnout syndrome frequency in this population. However, factors which were highly associated with physical and social consequences were: being male, aged 20 to 40, having a marital relationship with a habitual partner, working full-time, working at home and spending more than 75 % of the working day interacting with the beneficiaries of the services being provided.

Mercury: major issues in environmental health.

PubMed Central

Clarkson, T W

1993-01-01

In the past, methylmercury compounds were manufactured as fungicides or appeared as unwanted byproducts of the chemical industry, but today the methylation of inorganic mercury in aquatic sediments and soils is the predominant if not the sole source of methylmercury. This form of mercury is bioaccumulated to a high degree in aquatic food chains to attain its highest concentrations in edible tissues in long-lived predatory fish living in both fresh and ocean waters. It is well absorbed from the diet and distributes within a few days to all tissues in the body. It crosses without hindrance the blood-brain and placental barriers to reach its principal target tissue, the brain. It is eliminated chiefly in the feces after conversion to inorganic mercury. The biological half-time of methylmercury in human tissues is about 50 days, but there is wide individual variation. Adult poisoning is characterized by focal damage to discrete anatomical areas of the brain such as the visual cortex and granule layer of the cerebellum. A latent period of weeks or months may ensue before the appearance of signs and symptoms of poisoning. The latter manifest themselves as paresthesia, ataxia, constriction of the visual fields, and hearing loss. The prenatal period is the most sensitive stage of the life cycle to methylmercury. Prenatally poisoned infants exhibit a range of effects from severe cerebral palsy to subtle developmental delays. Methylmercury is believed to inhibit those processes in the brain specially involved in development and growth such as neuronal cell division and migration. PMID:8354179

Changes in Passive Tension of the Hamstring Muscles During a Simulated Soccer Match.

PubMed

Marshall, Paul W; Lovell, Ric; Siegler, Jason C

2016-07-01

Passive muscle tension is increased after damaging eccentric exercise. Hamstring-strain injury is associated with damaging eccentric muscle actions, but no research has examined changes in hamstring passive muscle tension throughout a simulated sport activity. The authors measured hamstring passive tension throughout a 90-min simulated soccer match (SAFT90), including the warm-up period and every 15 min throughout the 90-min simulation. Passive hamstring tension of 15 amateur male soccer players was measured using the instrumented straight-leg-raise test. Absolute torque (Nm) and slope (Nm/°) of the recorded torque-angular position curve were used for data analysis, in addition to total leg range of motion (ROM). Players performed a 15-min prematch warm-up, then performed the SAFT90 including a 15-min halftime rest period. Reductions in passive stiffness of 20-50° of passive hip flexion of 22.1-29.2% (P < .05) were observed after the warm-up period. During the SAFT90, passive tension increased in the latter 20% of the range of motion of 10.1-10.9% (P < .05) concomitant to a 4.5% increase in total hamstring ROM (P = .0009). The findings of this study imply that hamstring passive tension is reduced after an active warm-up that includes dynamic stretching but does not increase in a pattern suggestive of eccentric induced muscle damage during soccer-specific intermittent exercise. Hamstring ROM and passive tension increases are best explained by improved stretch tolerance.

Dynamic subcellular partitioning of the nucleolar transcription factor TIF-IA under ribotoxic stress.

PubMed

Szymański, Jedrzej; Mayer, Christine; Hoffmann-Rohrer, Urs; Kalla, Claudia; Grummt, Ingrid; Weiss, Matthias

2009-07-01

TIF-IA is a basal transcription factor of RNA polymerase I (Pol I) that is a major target of the JNK2 signaling pathway in response to ribotoxic stress. Using advanced fluorescence microscopy and kinetic modeling we elucidated the subcellular localization of TIF-IA and its exchange dynamics between the nucleolus, nucleoplasm and cytoplasm upon ribotoxic stress. In steady state, the majority of (GFP-tagged) TIF-IA was in the cytoplasm and the nucleus, a minor portion (7%) localizing to the nucleoli. We observed a rapid shuttling of GFP-TIF-IA between the different cellular compartments with a mean residence time of approximately 130 s in the nucleus and only approximately 30 s in the nucleoli. The import rate from the cytoplasm to the nucleus was approximately 3-fold larger than the export rate, suggesting an importin/exportin-mediated transport rather than a passive diffusion. Upon ribotoxic stress, GFP-TIF-IA was released from the nucleoli with a half-time of approximately 24 min. Oxidative stress and inhibition of protein synthesis led to a relocation of GFP-TIF-IA with slower kinetics while osmotic stress had no effect. The observed relocation was much slower than the nucleo-cytoplasmic and nucleus-nucleolus exchange rates of GFP-TIF-IA, indicating a time-limiting step upstream of the JNK2 pathway. In support of this, time-course experiments on the activity of JNK2 revealed the activation of the JNK kinase as the rate-limiting step.

Intravenous microemulsion of docetaxel containing an anti-tumor synergistic ingredient (Brucea javanica oil): formulation and pharmacokinetics.

PubMed

Ma, Shilin; Chen, Fen; Ye, Xiaohui; Dong, Yingjie; Xue, Yingna; Xu, Heming; Zhang, Wenji; Song, Shuangshuang; Ai, Li; Zhang, Naixian; Pan, Weisan

2013-01-01

The purpose of this study was to develop a docetaxel microemulsion containing an anti-tumor synergistic ingredient (Brucea javanica oil) and to investigate the characteristics of the microemulsion. Brucea javanica oil contains oleic acid and linoleic acids that have been shown by animal and human studies to inhibit tumor formation. The microemulsion containing Brucea javanica oil, medium-chain triglyceride, soybean lecithin, Solutol®HS 15, PEG 400, and water was developed for docetaxel intravenous administration. A formulation with higher drug content, lower viscosity, and smaller particle size was developed. The droplet size distribution of the dispersed phase of the optimized microemulsion was 13.5 nm, determined using a dynamic light scattering technique. The small droplet size enabled the microemulsion droplets to escape from uptake and phagocytosis by the reticuloendothelial system and increased the circulation time of the drug. The zeta potential was -41.3 mV. The optimized microemulsion was pale yellow, transparent, and non-opalescent in appearance. The value of the combination index was 0.58, showing that there was a synergistic effect when docetaxel was combined with Brucea javanica oil. After a single intravenous infusion dose (10 mg/kg) in male Sprague Dawley rats, the area under the curve of the microemulsion was higher and the half-time was longer compared with that of docetaxel solution alone, and showed superior pharmacokinetic characteristics. These results indicate that this preparation of docetaxel in emulsion is likely to provide an excellent prospect for clinical tumor treatment.

Polymorphic Crystallization and Crystalline Reorganization of Poly(l-lactic acid)/Poly(d-lactic acid) Racemic Mixture Influenced by Blending with Poly(vinylidene fluoride).

PubMed

Yu, Chengtao; Han, Lili; Bao, Jianna; Shan, Guorong; Bao, Yongzhong; Pan, Pengju

2016-08-18

The effects of poly(vinylidene fluoride) (PVDF) on the crystallization kinetics, competing formations of homocrystallites (HCs) and stereocomplexes (SCs), polymorphic crystalline structure, and HC-to-SC crystalline reorganization of the poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic mixture were investigated. Even though the PLLA/PDLA/PVDF blends are immiscible, blending with PVDF enhances the crystallization rate and SC formation of PLLA/PDLA components at different temperatures that are higher or lower than the melting temperature of the PVDF component; it also facilitates the HC-to-SC melt reorganization upon heating. The crystallization rate and degree of SC crystallinity (Xc,SC) of PLLA/PDLA components in nonisothermal crystallization increase after immiscible blending with PVDF. At different isothermal crystallization temperatures, the crystallization half-time of PLLA/PDLA components decreases; its spherulitic growth rate and Xc,SC increase as the mass fraction of PVDF increases from 0 to 0.5 in the presence of either a solidified or a molten PVDF phase. The HCs formed in primary crystallization of PLLA/PDLA components melt and recrystallize into SCs upon heating; the HC-to-SC melt reorganization is promoted after blending with PVDF. We proposed that the PVDF-promoted crystallization, SC formation, and HC-to-SC melt reorganization of PLLA/PDLA components in PLLA/PDLA/PVDF blends stem from the enhanced diffusion ability of PLLA and PDLA chains.

Pilot-scale experiment on anaerobic bioreactor landfills in China.

PubMed

Jiang, Jianguo; Yang, Guodong; Deng, Zhou; Huang, Yunfeng; Huang, Zhonglin; Feng, Xiangming; Zhou, Shengyong; Zhang, Chaoping

2007-01-01

Developing countries have begun to investigate bioreactor landfills for municipal solid waste management. This paper describes the impacts of leachate recirculation and recirculation loadings on waste stabilization, landfill gas (LFG) generation and leachate characteristics. Four simulated anaerobic columns, R1-R4, were each filled with about 30 tons of waste and recirculated weekly with 1.6, 0.8 and 0.2m(3) leachate and 0.1m(3) tap water. The results indicated that the chemical oxygen demand (COD) half-time of leachate from R1 was about 180 days, which was 8-14 weeks shorter than that of R2-R4. A large amount of LFG was first produced in R1, and its generation rate was positively correlated to the COD or volatile fatty acid concentrations of influent leachates after the 30th week. By the 50th week of recirculation, the waste in R1 was more stabilized, with 931.2 kg COD or 175.6 kg total organic carbon released and with the highest landfill gas production. However, this contributed mainly to washout by leachate, which also resulted in the reduction of LFG generation potential and accumulation of ammonia and/or phosphorus in the early stage. Therefore, the regimes of leachate recirculation should be adjusted to the phases of waste stabilization to enhance efficiency of energy recovery. Integrated with the strategy of in situ leachate management, extra pre-treatment or post-treatment methods to remove the nutrients are recommended.

The tissue residues of sodium dehydroacetate used as feed preservative in swine.

PubMed

Liu, Hao; Han, Lingling; Xie, Jiayu; Wu, Yingchao; Xie, Yang; Zhang, Yumei

2018-01-01

Sodium dehydroacetate (Na-DHA) is a food and feed additive with antimicrobial effects. There is little information on Na-DHA residue levels in foods derived from animals. In this study, Na-DHA residue levels in swine tissues were determined by HLPC, and the pharmacokinetics of Na-DHA in tissues were determined. The Na-DHA residue levels in swine tissues were <1.2 mg kg -1 at different withdrawal time after thirty-two Duroc × Landrace × Yorkshire pigs were administered 200 mg Na-DHA kg -1 through the feed for 30 days. In decreasing order of Na-DHA residue levels, the tissues were kidney > liver > muscle > fat. The pharmacokinetics of Na-DHA followed a binomial regression model, and the half-time of Na-DHA in swine tissues was 9.07 days for kidney, 7.19 days for liver, 6.66 days for muscle, and 5.39 days for fat tissue. The accuracy of the HPLC method for Na-DHA determination ranged from 80.18% to 91.33% recovery, with coefficients of variation <6.4%, limit of detection of 0.08 mg kg -1 , and limit of quantification of 0.2 mg kg -1 . Na-DHA included at 200 mg kg -1 in a swine diet is a safe feed additive based on residue elimination and ADI values reported. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Calcium-dependent transferrin receptor recycling in bovine chromaffin cells.

PubMed

Knight, Derek E

2002-04-01

The release of regulated secretory granules is known to be calcium dependent. To examine the Ca2+-dependence of other exocytic fusion events, transferrin recycling in bovine chromaffin cells was examined. Internalised 125I-transferrin was released constitutively from cells with a half-time of about 7 min. Secretagogues that triggered catecholamine secretion doubled the rate of 125I-transferrin release, the time courses of the two triggered secretory responses being similar. The triggered 125I-transferrin release came from recycling endosomes rather than from sorting endosomes or a triggered secretory vesicle pool. Triggered 125I-transferrin release, like catecholamine secretion from the same cells, was calcium dependent but the affinities for calcium were very different. The extracellular calcium concentrations that gave rise to half-maximal evoked secretion were 0.1 mm for 125I-transferrin and 1.0 mm for catecholamine, and the intracellular concentrations were 0.1 microm and 1 microm, respectively. There was significant 125I-transferrin recycling in the virtual absence of intracellular Ca2+, but the rate increased when Ca2+ was raised above 1 nm, and peaked at 1 microm when the rate had doubled. Botulinum toxin type D blocked both transferrin recycling and catecholamine secretion. These results indicate that a major component of the vesicular transport required for the constitutive recycling of transferrin in quiescent cells is calcium dependent and thus under physiological control, and also that some of the molecular machinery involved in transferrin recycling/fusion processes is shared with that for triggered neurosecretion.

Altered native stability is the dominant basis for susceptibility of α1-antitrypsin mutants to polymerization

PubMed Central

Irving, James A.; Haq, Imran; Dickens, Jennifer A.; Faull, Sarah V.; Lomas, David A.

2014-01-01

Serpins are protease inhibitors whose most stable state is achieved upon transition of a central 5-stranded β-sheet to a 6-stranded form. Mutations, low pH, denaturants and elevated temperatures promote this transition, which can result in a growing polymer chain of inactive molecules. Different types of polymer are possible, but, experimentally only heat has been shown to generate polymers in vitro consistent with ex vivo pathological specimens. Many mutations that alter the rate of heat-induced polymerization have been described, but interpretation is problematic because discrimination is lacking between the effect of global changes in native stability and specific effects on structural mechanism. We show that the temperature midpoint (Tm) of thermal denaturation reflects the transition of α1-antitrypsin to the polymerization intermediate, and determine the relationship with fixed-temperature polymerization half-times (t0.5) in the presence of stabilizing additives [TMAO (trimethylamine N-oxide), sucrose and sodium sulfate], point mutations and disulfide bonds. Combined with a retrospective analysis of 31 mutants characterized in the literature, the results of the present study show that global changes to native state stability are the predominant basis for the effects of mutations and osmolytes on heat-induced polymerization, summarized by the equation: ln(t0.5,mutant/t0.5,wild-type)=0.34×ΔTm. It is deviations from this relationship that hold key information about the polymerization process. PMID:24552432

Photocatalytic removal of perfluoroalkyl substances from water and wastewater: Mechanism, kinetics and controlling factors.

PubMed

Xu, Bentuo; Ahmed, Mohammad Boshir; Zhou, John L; Altaee, Ali; Wu, Minghong; Xu, Gang

2017-12-01

This review focuses on heterogeneous photocatalysis of perfluoroalkyl substances (PFAS) which are of worldwide concern as emerging persistent organic contaminants. Heterogeneous photocatalysis is an effective and advanced technology for PFAS removal from water with relatively high efficacy. During photocatalysis, various short chain perfluorocarboxylic acids (PFCA) are produced as intermediates and the efficacy is related to the photo-generated hole (h + ) and photo-generated electron (e - ). PFAS photodegradation in water under UV irradiation is most effective by using In 2 O 3 as the catalyst, followed by Ga 2 O 3 and TiO 2 . Significantly, modifying the chemical composition or morphology of the catalyst can improve its efficacy for PFAS removal. In 2 O 3 porous nanoplates were found to have the best performance of 100% PFAS decomposition under UV light with rate constant (k t ) and half-time (τ 1/2 ) of 0.158 min -1 and 4.4 min, respectively. Catalysts perform well in acidic solution and increasing temperature to a certain extent. The photocatalytic performance is reduced when treating wastewater due to the presence of dissolved organic matter (DOM), with the catalysts following the order: needle-like Ga 2 O 3  > In 2 O 3  > TiO 2 . Future studies should focus on the development of novel photocatalysts, and their immobilization and application for PFAS removal in wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Light-dependent quenching of chlorophyll fluorescence in pea chloroplasts induced by adenosine 5'-triphosphate.

PubMed

Horton, P; Black, M T

1981-03-12

Addition of ATP to chloroplasts causes a reversible 25-30% decrease in chlorophyll fluorescence. This quenching is light-dependent, uncoupler insensitive but inhibited by DCMU and electron acceptors and has a half-time of 3 minutes. Electron donors to Photosystem I can not overcome the inhibitory effect of DCMU, suggesting that light activation depends on the reduced state of plastoquinone. Fluorescence emission spectra recorded at -196 degrees C indicate that ATP treatment increases the amount of excitation energy transferred to Photosystem I. Examination of fluorescence induction curves indicate that ATP treatment decreases both the initial (F0) and variable (Fv) fluorescence such that the ratio of Fv to the maximum (Fm) yield is unchanged. The initial sigmoidal phase of induction is slowed down by ATP treatment and is quenched 3-fold more than the exponential slow phase, the rate of which is unchanged. A plot of Fv against area above the induction curve was identical plus or minus ATP. Thus ATP treatment can alter quantal distribution between Photosystems II and I without altering Photosystem II-Photosystem II interaction. The effect of ATP strongly resembles in its properties the phosphorylation of the light-harvesting complex by a light activated, ATP-dependent protein kinase found in chloroplast membranes and could be the basis of physiological mechanisms which contribute to slow fluorescence quenching in vivo and regulate excitation energy distribution between Photosystem I and II. It is suggested that the sensor for this regulation is the redox state of plastoquinone.

Optimization of mNeonGreen for Homo sapiens increases its fluorescent intensity in mammalian cells.

PubMed

Tanida-Miyake, Emiko; Koike, Masato; Uchiyama, Yasuo; Tanida, Isei

2018-01-01

Green fluorescent protein (GFP) is tremendously useful for investigating many cellular and intracellular events. The monomeric GFP mNeonGreen is about 3- to 5-times brighter than GFP and monomeric enhanced GFP and shows high photostability. The maturation half-time of mNeonGreen is about 3-fold faster than that of monomeric enhanced GFP. However, the cDNA sequence encoding mNeonGreen contains some codons that are rarely used in Homo sapiens. For better expression of mNeonGreen in human cells, we synthesized a human-optimized cDNA encoding mNeonGreen and generated an expression plasmid for humanized mNeonGreen under the control of the cytomegalovirus promoter. The resultant plasmid was introduced into HEK293 cells. The fluorescent intensity of humanized mNeonGreen was about 1.4-fold higher than that of the original mNeonGreen. The humanized mNeonGreen with a mitochondria-targeting signal showed mitochondrial distribution of mNeonGreen. We further generated an expression vector of humanized mNeonGreen with 3xFLAG tags at its carboxyl terminus as these tags are useful for immunological analyses. The 3xFLAG-tagged mNeonGreen was recognized well with an anti-FLAG-M2 antibody. These plasmids for the expression of humanized mNeonGreen and mNeonGreen-3xFLAG are useful tools for biological studies in mammalian cells using mNeonGreen.

Comparative investigations of the biodurability of mineral fibers in the rat lung.

PubMed Central

Muhle, H; Bellmann, B; Pott, F

1994-01-01

The biodurability of various glass fibers, rockwool, and ceramic fibers was examined in rat lungs and compared with natural mineral fibers. Experiments were based on studies that have shown that the biodurability of fibers is one of the essential factors of the carcinogenic potency of these materials. Sized fractions of fibers were instilled intratracheally into Wistar rats. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM) or careful examination of the fiber suspension before treatment. After serial sacrifices up to 24 months after treatment, the fibers were analyzed by SEM following low temperature ashing of the lungs. Parameters measured included number of fibers, diameter, and length distribution at the various sacrifice dates, so that analyses could be made of the elimination kinetics of fibers from the lung in relation to fiber length (FL). Size selective plots of the fiber elimination correlated with fiber diameters enables the mechanism of the fiber elimination (dissolution, fiber breakage, physical clearance) to be interpreted. The half-time of fiber elimination from the lung ranges from about 10 days for wollastonite to more than 300 days for crocidolite. The biodurability of man-made vitreous fibers (MMVF) is between these values and is dependent on the chemical composition of the fibers and the diameter and length distribution. Results indicate that the in vivo durability of glass fibers is considerably longer than expected from extrapolation of published data on their in vitro dissolution rates. PMID:7882923

Exploring Variation in Teenage Mothers’ and Fathers’ Educational Attainment

PubMed Central

Mollborn, Stefanie

2011-01-01

CONTEXT A substantial body of research has compared educational outcomes of teenage parents with those of their childless peers, but less attention has gone to variations among teenage parents. Additionally, gender differences in teenage parents’ educational outcomes have rarely been studied. METHODS Characteristics associated with high school graduation by age 26 were assessed among 317 teenage mothers and fathers who participated in the 1988–2000 National Education Longitudinal Study. Logistic regression models included socioeconomic and educational characteristics, gender, parenting responsibilities and resources, and gender interactions. RESULTS Married or cohabiting teenage parents living with no or one parent had 73% lower odds of graduation than single respondents living with two parents. Gender moderated the relationships between two parenting responsibilities and the likelihood of graduation: Fathers working at least half-time were less likely than nonworking fathers to graduate (odds ratio, 0.2), and fathers who were primary caregivers had substantially elevated odds of graduating (7.4), but no similar relationships were seen among mothers. Sixty-one percent of fathers who worked but were not primary care-givers were predicted to graduate by age 26, compared with 97% of those who were nonworking primary caregivers. CONCLUSIONS Traditional parenting norms, according to which mothers are primary caregivers and fathers are breadwinners, do not appear to be associated with improved odds of graduating. Policies and interventions aimed at helping teenage parents graduate may be most effective if they target both genders, but some are likely to be more beneficial for one gender than the other. PMID:20887284

Na+/Ca2+ exchange in cardiac myocytes. Effect of ouabain on voltage dependence.

PubMed

Lee, H C; Clusin, W T

1987-02-01

Sarcolemmal sodium/calcium exchange activity was examined in individual chick embryonic myocardial cell aggregates that were loaded with quin 2. The baseline [Ca2+]i was 68 +/- 4 nM (n = 29). Abrupt superfusion with sodium-free lithium solution produced a fourfold increase in steady-state [Ca2+]i to 290 +/- 19 nM, which was reversible upon sodium restitution. Other methods of increasing [Ca2+]i such as KCl-depolarization or caffeine produced a dose-dependent increase in quin 2 fluorescence, accompanied by sustained contracture. The [Ca2+]i increase in zero sodium was linear, and its half-time (t1/2) of 15.1 +/- 0.1 s was similar to that of the sodium-free contracture (t1/2 = 14.4 +/- 0.5 s) under the same conditions. The sodium-dependent [Ca2+]i increase was not significantly greater when potassium served as the sodium substitute instead of lithium. This suggests that sodium/calcium exchange has little voltage dependence in this situation. However, in aggregates pretreated with ouabain (2.5 microM), the [Ca2+]i increase was almost threefold greater with potassium than with lithium (P less than 0.007). Ouabain therefore potentiated the effect of membrane potential on calcium influx. We propose that elevation of [Na2+]i is a prerequisite for voltage dependence of the sodium/calcium exchange under the conditions studied. Sodium loading will then drastically increase calcium influx during the action potential while inducing an outward membrane current that could accelerate repolarization.

Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats.

PubMed

Hureaux, José; Lacoeuille, Franck; Lagarce, Frédéric; Rousselet, Marie-Christine; Contini, Aurélien; Saulnier, Patrick; Benoit, Jean-Pierre; Urban, Thierry

2017-01-01

Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf ® in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy.

Water-in-Water Emulsion Based Synthesis of Hydrogel Nanospheres with Tunable Release Kinetics

NASA Astrophysics Data System (ADS)

Aydın, Derya; Kızılel, Seda

2017-07-01

Poly(ethylene glycol) (PEG) micro/nanospheres have several unique advantages as polymer based drug delivery systems (DDS) such as tunable size, large surface area to volume ratio, and colloidal stability. Emulsification is one of the widely used methods for facile synthesis of micro/nanospheres. Two-phase aqueous system based on polymer-polymer immiscibility is a novel approach for preparation of water-in-water (w/w) emulsions. This method is promising for the synthesis of PEG micro/nanospheres for biological systems, since the emulsion is aqueous and do not require organic solvents or surfactants. Here, we report the synthesis of nano-scale PEG hydrogel particles using w/w emulsions using phase separation of dextran and PEG prepolymer. Dynamic light scattering (DLS) and scaning electron microscopy (SEM) results demonstrated that nano-scale hydrogel spheres could be obtained with this approach. We investigated the release kinetics of a model drug, pregabalin (PGB) from PEG nanospheres and demonstrated the influence of polymerization conditions on loading and release of the drug as well as the morphology and size distribution of PEG nanospheres. The experimental drug release data was fitted to a stretched exponential function which suggested high correlation with experimental results to predict half-time and drug release rates from the model equation. The biocompatibility of nanospheres on human dermal fibroblasts using cell-survival assay suggested that PEG nanospheres with altered concentrations are non-toxic, and can be considered for controlled drug/molecule delivery.

Alterations in myocardial free fatty acid clearance precede mechanical abnormalities in canine tachycardia-induced heart failure.

PubMed

Freeman, G L; Colston, J T; Miller, D D

1994-01-01

The purpose of this study was to evaluate whether abnormalities of free fatty acid metabolism are present before the onset of overt mechanical dysfunction in dogs with tachycardia-induced heart failure. We studied six dogs chronically instrumented to allow assessment of left ventricular function in the pressure-volume plane. Free fatty acid clearance was assessed according to the washout rate of a free fatty acid analog, iodophenylpentadecanoic acid ([123I]PPA or IPPA). IPPA clearance was measured within 1 hour of the hemodynamic assessment. The animals were studied under baseline conditions and 11.7 +/- 3.6 days after ventricular pacing at a rate of 240 beats/min. Hemodynamic studies after pacing showed a nonsignificant increase in left ventricular end-diastolic pressure (11.7 +/- 4.7 to 17.4 +/- 6.5 mm Hg) and a nonsignificant decrease in the maximum derivative of pressure with respect to time (1836 +/- 164 vs 1688 +/- 422 mm Hg/sec). There was also no change in the time constant of left ventricular relaxation, which was 34.8 +/- 7.67 msec before and 35.3 +/- 7.3 msec after pacing. However, a significant prolongation in the clearance half-time of [123I]PPA, from 86.1 +/- 23.9 to 146.5 +/- 22.6 minutes (p < 0.01) was found. Thus abnormal lipid clearance appears before the onset of significant mechanical dysfunction in tachycardia-induced heart failure. This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition.

[Analysis of decompression safety during extravehicular activity of astronauts in the light of probability theory].

PubMed

Nikolaev, V P; Katuntsev, V P

1998-01-01

Objectives of the study were comparative assessment of the risk of decompression sickness (DCS) in human subjects during shirt-sleeve simulation of extravehicular activity (EVA) following Russian and U.S. protocols, and analysis of causes of the difference between real and simulated EVA decompression safety. To this end, DCS risk during exposure to a sing-step decompression was estimated with an original method. According to the method, DCS incidence is determined by distribution of nucleation efficacy index (z) in the worst body tissues and its critical values (zm) as a function of initial nitrogen tension in these tissues and final ambient pressure post decompression. Gaussian distribution of z values was calculated basing on results of the DCS risk evaluation on the U.S. EVA protocol in an unsuited chamber test with various pre-breath procedures (Conkin et al., 1987). Half-time of nitrogen washout from the worst tissues was presumed to be 480 min. Calculated DCS risk during short-sleeve EVA simulation by the Russian and U.S. protocols with identical physical loading made up 19.2% and 23.4%, respectively. Effects of the working spacesuit pressure, spacesuit rigidity, metabolic rates during operations in EVA space suit, transcutaneous nitrogen exchange in the oxygen atmosphere of space suit, microgravity, analgesics, short compression due to spacesuit leak tests on the eye of EVA are discussed. Data of the study illustrate and advocate for high decompression safety of current Russian and U.S. EVA protocols.

Transition In Supersonic Flows With Corners

NASA Technical Reports Server (NTRS)

Balakumar, P.; McClinton, Charles (Technical Monitor)

2001-01-01

It is proposed to investigate the effect of sudden change in the slope of the surface on the stability and transition onset point in supersonic and hypersonic boundary layers. Since we can not use the linear stability theory in flows where there are discontinuities we have to solve the full Navier-Stokes equations to determine the amplification of the disturbances across the oblique shock which exists at the corner. We will use the Navier-Stokes code which was developed by Dr. Harold Atkins in the aerodynamic and acoustic methods branch. The code is developed using the higher order ENO scheme and is currently set up for two-dimensional flows. In the first year of our investigation, we will investigate the evolution of small amplitude two-dimensional disturbances and determine the N-factors for the most amplified disturbances. We will perform the analysis for the parameter similar to X-31 model and flight experiment conditions. From these computation we will infer what is the maximum amplification rate possible in quite environments without any tripping devices. In the second part of the investigation, we will perform nonlinear computations to determine what is the minimum amplitudes necessary to cause the transition at a designed location. In the third part, we have to determine what kind of trip devices necessary to excite the required disturbances. The principal investigator of this project is Dr. P. Balakumar, Associate Professor of Department of Aerospace Engineering, Old Dominion University. We will actively collaborate with research scientists in the Aero-Thermodynamics Branch at NASA/Langley Research Center. A half-time graduate student will also participate in the project.

Low-temperature tolerance and cold hardening of cacti

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nobel, P.S.

Reduced uptake by the chlorenchyma cells of cacti of a stain (neutral red) was used as an indicator of low-temperature damage resulting from cooling stems in the laboratory. Necrosis set in a few degrees below the temperature at which the fraction of cells accumulating stain was reduced by 50%. Coryphantha vivipara, Opuntia polyacantha, and Pediocactus simpsonii, which range to over 300 m altitude in southern Wyoming, were quite cold tolerant. Relationships among tissue cold sensitivity, morphological features which protect the stems from low temperatures, and the occurrence of species in progressively colder regions were investigated. Differences in tissue cold sensitivitymore » accounted for the approx. = 600 m higher elevational limit of Coryphantha vivipara var. rosea compared to the morphologically similar var. deserti in southern Nevada. In contrast, morphological differences alone could adequately explain the relative northern limits of the columnar cacti Carnegiea gigantea vs Stenocereus gummosus and the barrel cacti Ferocactus acanthodes vs. F. wislizenii in the southwestern United States, as previously indicated using a computer model. Cold hardening in response to decreasing day/night air temperatures was observed for 10 species. A decrease from 50/sup 0//40/sup 0/ to 10/sup 0//0/sup 0/ lowered by 4/sup 0/ the temperature at which the fraction of the chlorenchyma cells taking up stain was reduced 50% for both D. rhodacantha and T. candicans, with a half-time for the shift of approx. = 3 d. The tolerance of subzero temperatures and the ability to cold harden allow cacti to range into regions with considerable wintertime freezing.« less

Positive effect of specific low-frequency electrical stimulation during short-term recovery on subsequent high-intensity exercise.

PubMed

Bieuzen, François; Borne, Rachel; Toussaint, Jean-François; Hausswirth, Christophe

2014-02-01

The objective of this study was to test how low-frequency electrical stimulation (LFES; Veinoplus Sport (AdRem Technology, Paris, France)) of the calf muscles affects recovery indices compared with 2 other commonly used recovery methods (active, ACT; passive, PAS). The tests used assessed predominantly anaerobic performance after short-term (15 min) recovery, and the kinetics of blood markers. Fourteen highly trained female handball players completed 2 Yo-Yo Intermittent Recovery tests (level 2; YYIR2) separated by a 15-min recovery period. During recovery, 1 of 3 recovery methods (ACT, LFES or PAS) was randomly selected. Performance (i.e., distance run) was measured at the end of each YYIR2 test. Blood lactate, pH, bicarbonate concentrations, heart rate, respiratory gas exchange and tissue saturation index for the lateral gastrocnemius were recorded. LFES showed a very likely beneficial effect on performance during the second YYIR2 relative to PAS and a possible beneficial effect relative to ACT (distance Pre vs. Post; LFES: -1.8%; ACT: -7.6%; PAS: -15.9%). Compared with PAS recovery, LFES and ACT recovery clearly showed a faster return to baseline for blood lactate, pH and bicarbonate concentrations during the recovery period. LFES of the calf muscles and, to a lesser extent, ACT recovery appear to effectively improve short-term recovery between 2 bouts of exhausting exercises. These methods could be of benefit if applied during half-time, for sports involving successive rounds, or where only a limited recovery period is available.

gp160 of HIV-I synthesized by persistently infected Molt-3 cells is terminally glycosylated: evidence that cleavage of gp160 occurs subsequent to oligosaccharide processing.

PubMed

Merkle, R K; Helland, D E; Welles, J L; Shilatifard, A; Haseltine, W A; Cummings, R D

1991-10-01

The envelope glycoprotein of HIV-I in infected, cultured human T cells is synthesized as a precursor of apparent Mr 160 kDa (gp160) and is cleaved to two glycoproteins, gp120 and gp41, which are the mature envelope glycoproteins in the virus. Neither the temporal and spatial features of glycosylation nor the oligosaccharide processing and proteolytic cleavage of the envelope glycoprotein are well understood. To understand more about these events, we investigated the glycosylation and cleavage of the envelope glycoproteins in the CD4+ human cell line, Molt-3, persistently infected with HIV-I (HTLV IIIB). The carbohydrate analysis of gp160 and gp120 and the behavior of the glycoproteins and glycopeptides derived from them on immobilized lectins demonstrate that both of these glycoproteins contain complex- and high-mannose-type Asn-linked oligosaccharides. In addition, the N-glycanase-resistant oligosaccharides of gp120 were found to contain N-acetyl-galactosamine, a common constituent of Ser/Thr-linked oligosaccharides. Pulse-chase analysis of the conversion of [35S]cysteine-labeled gp160 showed that in Molt-3 cells it takes about 2 h for gp120 to arise with a half-time of conversion of about 5 h. At its earliest detectable occurrence, gp120 was found to contain complex-type Asn-linked oligosaccharides. Taken together, these results indicate that proteolytic cleavage of gp160 to gp120 and gp41 occurs either within the trans-Golgi or in a distal compartment.

Production and characterization of a novel long-acting Herceptin-targeted nanobubble contrast agent specific for Her-2-positive breast cancers.

PubMed

Jiang, Qiongchao; Hao, Shaoyun; Xiao, Xiaoyun; Yao, Jiyi; Ou, Bing; Zhao, Zizhuo; Liu, Fengtao; Pan, Xin; Luo, Baoming; Zhi, Hui

2016-05-01

There is an unmet need for specific and sensitive imaging techniques to assess the efficacy of breast cancer therapy, particularly Her-2-expressing cancers. Ultrasonic microbubbles are being developed for use as diagnostic and therapeutic tools. However, nanobubbles circulate longer, are smaller, and diffuse into extravascular tissue to specifically bind target molecules. Here, we characterize a novel Herceptin-conjugated nanobubble for use against Her-2-expressing tumors. Phospholipid-shelled nanobubbles conjugated with Herceptin (NBs-Her) were fabricated using a thin-film hydration method and characterized in vitro in breast cancer cell lines and in vivo in a mouse model. The average size of the unconjugated nanobubbles (NBs-Blank) and NBs-Her was 447.1 ± 18.4 and 613.0 ± 25.4 nm, respectively. In cell culture, the NBs-Her adhered to Her-2-positive cells significantly better than to Her-2-negative cells (p < 0.05). In vivo, the peak intensity and the half-time to washout of the NBs-Her were significantly greater than those of the NBs-Blank (p < 0.05). In addition, contrast-enhanced ultrasound imaging quality was improved through the use of the NBs-Her. The nanobubbles were able to penetrate into tumor tissue to allow extravascular imaging, but did not penetrate normal skeletal muscle. The Herceptin-conjugated nanobubble had many properties that made it useful for in vivo imaging, including longer circulation time and better tumor selectivity. This platform may be able to provide targeted delivery of therapeutic drugs or genes.

Effect of gum chewing on gastric volume and emptying: a prospective randomized crossover study.

PubMed

Bouvet, L; Loubradou, E; Desgranges, F-P; Chassard, D

2017-11-01

Current fasting guidelines allow oral intake of water up to 2 h before induction of anaesthesia. We assessed whether gum chewing affects gastric emptying of 250 ml water and residual gastric fluid volume measured 2 h after ingestion of water. This prospective randomized observer-blind crossover trial was performed on 20 healthy volunteers who attended two separate study sessions: Control and Chewing gum (chlorophyll flavour, with 2.1 g carbohydrate). Each session started with an ultrasound measurement of the antral area, followed by drinking 250 ml water. Then, volunteers either chewed a sugared gum for 45 min (Chewing gum) or did not (Control). Serial measurements of the antral area were performed during 120 min, and the half-time to gastric emptying (t½), total gastric emptying time, and gastric fluid volume before ingestion of water and 120 min later were calculated. Gastric emptying of water was not different between sessions; the mean (sdsd) t½ was 23 (10) min in the Control session and 21 (7) min in the Chewing gum session (P=0.52). There was no significant difference between sessions in gastric fluid volumes measured before ingestion of water and 120 min later. Chewing gum does not affect gastric emptying of water and does not change gastric fluid volume measured 2 h after ingestion of water. NCT02673307. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Comparative structure-function characterization of the saposin-like domains from potato, barley, cardoon and Arabidopsis aspartic proteases.

PubMed

Bryksa, Brian C; Grahame, Douglas A; Yada, Rickey Y

2017-05-01

The present study characterized the aspartic protease saposin-like domains of four plant species, Solanum tuberosum (potato), Hordeum vulgare L. (barley), Cynara cardunculus L. (cardoon; artichoke thistle) and Arabidopsis thaliana, in terms of bilayer disruption and fusion, and structure pH-dependence. Comparison of the recombinant saposin-like domains revealed that each induced leakage of bilayer vesicles composed of a simple phospholipid mixture with relative rates Arabidopsis>barley>cardoon>potato. When compared for leakage of bilayer composed of a vacuole-like phospholipid mixture, leakage was approximately five times higher for potato saposin-like domain compared to the others. In terms of fusogenic activity, distinctions between particle size profiles were noted among the four proteins, particularly for potato saposin-like domain. Bilayer fusion assays in reducing conditions resulted in altered fusion profiles except in the case of cardoon saposin-like domain which was virtually unchanged. Secondary structure profiles were similar across all four proteins under different pH conditions, although cardoon saposin-like domain appeared to have higher overall helix structure. Furthermore, increases in Trp emission upon protein-bilayer interactions suggested that protein structure rearrangements equilibrated with half-times ranging from 52 to 120s, with cardoon saposin-like domain significantly slower than the other three species. Overall, the present findings serve as a foundation for future studies seeking to delineate protein structural features and motifs in protein-bilayer interactions based upon variability in plant aspartic protease saposin-like domain structures. Copyright © 2017 Elsevier B.V. All rights reserved.

Concentration dependent switch in the kinetic pathway of lysozyme fibrillation: Spectroscopic and microscopic analysis

NASA Astrophysics Data System (ADS)

Kiran Kumar, E.; Prasad, Deepak Kumar; Prakash Prabhu, N.

2017-08-01

Formation of amyloid fibrils is found to be a general tendency of many proteins. Investigating the kinetic mechanisms and structural features of the intermediates and the final fibrillar state is essential to understand their role in amyloid diseases. Lysozyme, a notable model protein for amyloidogenic studies, readily formed fibrils in vitro at neutral pH in the presence of urea. It, however, showed two different kinetic pathways under varying urea concentrations when probed with thioflavin T (ThT) fluorescence. In 2 M urea, lysozyme followed a nucleation-dependent fibril formation pathway which was not altered by varying the protein concentration from 2 mg/ml to 8 mg/ml. In 4 M urea, the protein exhibited concentration dependent change in the mechanism. At lower protein concentrations, lysozyme formed fibrils without any detectable nuclei (nucleation-independent polymerization pathway). When the concentration of the protein was increased above 3 mg/ml, the protein followed nucleation-dependent polymerization pathway as observed in the case of 2 M urea condition. This was further verified using microscopic images of the fibrils. The kinetic parameters such as lag time, elongation rate, and fibrillation half-time, which were derived from ThT fluorescence changes, showed linear dependency against the initial protein concentration suggested that under the nucleation-dependent pathway conditions, the protein followed primary-nucleation mechanism without any significant secondary nucleation events. The results also suggested that the differences in the initial protein conformation might alter the mechanism of fibrillation; however, at the higher protein concentrations lysozyme shifted to nucleation-dependent pathway.

An assay of behavioral plasticity in Drosophila larvae

PubMed Central

Min, Virginia A.; Condron, Barry G.

2010-01-01

Stress, or threats to homeostasis, is a universal part of life. Organisms face changing and challenging situations everyday, and the ability to respond to such stress is essential for survival. When subjected to acute stress, the body responds molecularly and behaviorally in order to recover a steady state. We developed a simple and robust assay of behavioral plasticity for Drosophila larvae in which well-defined behavioral responses and recovery can be observed and quantified. After experiencing different control and bright light treatments, populations of photophobic fly larvae were placed a defined distance from a food source to which they crawled. Half-times (t½), or times at which half the total number of larvae reached the food, were used to compare different treatments and larval populations. Repeated control treatments with a main experimental strain gave tight, reproducible t½ ranges. Control treatments with the wild type strains Oregon R and Canton S, the “rover” and “sitter” alleles of the forager locus, and eyeless mutants gave comparable results to those of the experimental strain. Exposure to bright light for a defined time period resulted in a reproducible slowing of locomotion. However, given a defined recovery period, the larvae recover full, normal locomotion. In addition, bright light treatments with Canton S gave comparable results to those of the experimental strain. Eyeless mutants, which are partially blind, do not show a response to bright light treatment. Thus, our assay measures the behavioral responses to bright light in Drosophila larvae and therefore might be useful as a general assay for studying behavioral plasticity and, potentially, adaptation to a stressful stimulus. PMID:15922026

Spatial and temporal distribution of airborne Bacillus thuringiensis var. kurstaki during an aerial spray program for gypsy moth eradication.

PubMed

Teschke, K; Chow, Y; Bartlett, K; Ross, A; van Netten, C

2001-01-01

We measured airborne exposures to the biological insecticide Bacillus thuringiensis var. kurstaki (Btk) during an aerial spray program to eradicate gypsy moths on the west coast of Canada. We aimed to determine whether staying indoors during spraying reduced exposures, to determine the rate of temporal decay of airborne concentrations, and to determine whether drift occurred outside the spray zone. During spraying, the average culturable airborne Btk concentration measured outdoors within the spray zone was 739 colony-forming units (CFU)/m3 of air. Outdoor air concentrations decreased over time, quickly in an initial phase with a half time of 3.3 hr, and then more slowly over the following 9 days, with an overall half-time of about 2.4 days. Inside residences during spraying, average concentrations were initially 2-5 times lower than outdoors, but at 5-6 hr after spraying began, indoor concentrations exceeded those outdoors, with an average of 244 CFU/m3 vs. 77 CFU/m3 outdoors, suggesting that the initial benefits of remaining indoors during spraying may not persist as outside air moves indoors with normal daily activities. There was drift of culturable Btk throughout a 125- to 1,000-meter band outside the spray zone where measurements were made, a consequence of the fine aerosol sizes that remained airborne (count median diameters of 4.3 to 7.2 microm). Btk concentrations outside the spray zone were related to wind speed and direction, but not to distance from the spray zone.

When what appears to be mitral stenosis is not: diagnostic and therapeutic implications.

PubMed

Almeida, Inês; Caetano, Francisca; Trigo, Joana; Mota, Paula; Cachulo, Maria do Carmo; Antunes, Manuel; Leitão Marques, António

2014-01-01

The authors report the case of a 53-year-old man, with a long-standing history of mild mitral stenosis, admitted for worsening fatigue. Transthoracic echocardiography (limited by poor image quality) showed mitral annular calcification, leaflets that were difficult to visualize and an estimated mitral valve area of 1.8 cm(2) by the pressure half-time method. However, elevated mean transmitral and right ventricle/right atrium gradients were identified (39 and 117 mmHg, respectively). This puzzling discrepancy in the echocardiographic findings prompted investigation by transesophageal echocardiography, which revealed an echogenic structure adjacent to the mitral annulus, causing severe obstruction (effective orifice area 0.7 cm(2)). The suspicion of supravalvular mitral ring was confirmed during surgery. Following ring resection and mitral valve replacement there was significant improvement in the patient's clinical condition and normalization of the left atrium/left ventricle gradient. Supravalvular mitral ring is an unusual cause of congenital mitral stenosis, characterized by an abnormal ridge of connective tissue on the atrial side of the mitral valve, which often obstructs mitral valve inflow. Few cases have been reported, most of them in children with concomitant congenital abnormalities. Diagnosis of a supravalvular mitral ring is challenging, since it is very difficult to visualize in most diagnostic tests. It was the combination of clinical and various echocardiographic findings that led us to suspect this very rare condition, enabling appropriate treatment, with excellent long-term results. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Resident evaluation of clinical teachers based on teachers' certification.

PubMed

Steiner, Ivan P; Yoon, Philip W; Kelly, Karen D; Diner, Barry M; Donoff, Michel G; Mackey, Duncan S; Rowe, Brian H

2003-07-01

To examine the influence of emergency medicine (EM) certification of clinical teaching faculty on evaluations provided by residents. A prospective cohort analysis was conducted of assessments between July 1994 and July 2000 on residents' evaluations of EM faculty at the University of Alberta, Edmonton, Canada. Resident- and faculty-related variables were entered anonymously using the validated evaluation tool (ER Scale). Credentialing and demographic information on EM faculty was supplemented by data obtained through a nine-question survey. Groups were compared using ANOVA. The 562 residents returned 705 (91%) valid evaluation sheets on 115 EM faculty members. The four domains of didactic teaching, clinical teaching, approachability, and helpfulness were assessed. The majority of ratings were in the very good or superb categories for each domain. Instructors with certification in EM had higher scores in didactic, clinical teaching compared with others, and teachers without national certification scored lower in the helpful and approachable categories (p < 0.05). The route of obtaining EM certifications either through training or practice eligibility did not affect scores. Instructors under the age of 40 years had higher scores than the older age groups in three of four categories (p < 0.05). Instructors working at the teaching sites on a half-time basis received higher scores than those working full-time, and scores varied based on site. Overall, teaching ratings improved over the study period (p < 0.05). Significant differences exist among instructors in the EM setting that affect their teaching rating scores. National certification in EM, academic track, rotation year, and site are all correlated with better teaching performance.

Emergency department provider preferences related to clinical practice guidelines for tobacco cessation: a multicenter survey.

PubMed

Walters, Elizabeth L; Reibling, Ellen T; Wilber, Scott T; Sullivan, Ashley F; Gaeta, Theodore J; Camargo, Carlos A; Boudreaux, Edwin D

2014-07-01

The objective was to assess current emergency department (ED) provider practices and preferences for tobacco cessation interventions. The ED is an opportune place to initiate smoking cessation interventions. However, little is known about ED provider current practices and preferences for cessation counseling in the ED. This was a survey of ED providers conducted in 2008-2009 (including physicians, nurse practitioners, physician assistants, and nurses), working at least half-time at 10 U.S. academic EDs, regarding adherence to clinical practice guidelines ("5 As") and preferences for cessation interventions/styles. Data analysis occurred in 2012-2013. The response rate was 64% (800 out of 1,246 completed surveys). Providers reported strongest adherence to asking about patient smoking status, followed by advising, with significant variance by clinical role. Assessing, assisting, and arranging support for patients was low overall. Most frequently used interventions were to provide patients with a list of telephone numbers for stop-smoking counseling (87%), pamphlets on smoking health risks and the benefits of stopping (85%), and referrals to the National Toll-Free Smoker's Quitline (84%). Most providers (80%) were supportive of personally conducting brief (less than 3 minutes) smoking cessation counseling sessions during the ED visit, emphasizing education and encouragement. The least appealing intervention was writing a prescription for nicotine replacement therapies or medications to stop smoking (35%). Interventions most likely to be used were brief and delivered with a positive tone and included referral to external resources. The logical next step is to design and test interventions that ED providers find acceptable. © 2014 by the Society for Academic Emergency Medicine.

Reproduction of bobwhites fed different dietary concentrations of an organophosphate insecticide, methamidophos

USGS Publications Warehouse

Stromborg, K.L.

1986-01-01

Pairs of first-year breeding bobwhites were fed constant or variable concentrations of methamidophos for 15 days, or a control diet in a pair-fed design in which they were matched by body weights to pairs in the constant group. Treatments for the constant group were 5.0, 7.8, 12.3, 19.2, and 30.0 ppm for 5 pairs at each concentration. The number of pairs per concentration and peak concentrations for the variable pairs were identical to the constant dosages. Concentrations for the variable group were increased by a factor of four during two 3-day periods in order to reach the peak concentrations on days 7?9 after which they were decreased by 18% every 3 days to correspond to an environmental half-time of 10.5 days. Food consumption, egg production, hatchability of eggs under artificial incubation, and survival of hatched chicks for 2 weeks were recorded for each pair during 15-day treatment and 21-day posttreatment periods. Mortality was high in the highest constant dosage (2/10) and the associated pair-fed groups (3/10). Food consumption and egg production rates were negatively dose-related during the treatment period in the constant and variable groups. The laying rate of pair-fed hens was reduced to the same extent as in the constant group. Reproductive inhibition was not permanent and pairs resumed laying after a dose-related recovery interval. No dose-related effects on hatchability or chick survival were detected. Furthermore, there was no evidence of a pesticide effect on reproduction in addition to that exerted through pesticide-induced anorexia.

Design and characterization of Amoitone B-loaded nanostructured lipid carriers for controlled drug release.

PubMed

Luan, Jingjing; Zhang, Dianrui; Hao, Leilei; Li, Caiyun; Qi, Lisi; Guo, Hejian; Liu, Xinquan; Zhang, Qiang

2013-11-01

Amoitone B, a novel compound chemically synthesized as the analogue of cytosporone B, has been proved to own superior affinity with Nur77 than its parent compound and exhibit notable anticancer activity. However, its application is seriously restricted due to the water-insolubility and short biological half-time. The aim of this study was to construct an effective delivery system for Amoitone B to realize sustained release, thus prolong drug circulation time in body and improve the bioavailability. Nanostructured lipid carriers (NLC) act as a new type of colloidal drug delivery system, which offer the advantages of improved drug loading and sustained release. Amoitone B-loaded NLC (AmB-NLC) containing glyceryl monostearate (GMS) and various amounts of medium chain triglycerides (MCT) were successfully prepared by emulsion-evaporation and low temperature-solidification technology with a particle size of about 200 nm and a zeta potential value of about -20 mV. The results of X-ray diffraction and DSC analysis showed amorphous crystalline state of Amoitone B in NLC. Furthermore, the drug entrapment efficacy (EE) was improved compared with solid lipid nanoparticles (SLN). The EE range was from 71.1% to 84.7%, enhanced with the increase of liquid lipid. In vitro drug release studies revealed biphasic drug release patterns with burst release initially and prolonged release afterwards and the release was accelerated with augment of liquid lipid. These results demonstrated that AmB-NLC could be a promising delivery system to control drug release and improve loading capacity, thus prolong drug action time in body and enhance the bioavailability.

Release of beryllium from mineral ores in artificial lung and skin surface fluids.

PubMed

Duling, Matthew G; Stefaniak, Aleksandr B; Lawrence, Robert B; Chipera, Steve J; Virji, M Abbas

2012-06-01

Exposure to some manufactured beryllium compounds via skin contact or inhalation can cause sensitization. A portion of sensitized persons who inhale beryllium may develop chronic beryllium disease (CBD). Little is understood about exposures to naturally occurring beryllium minerals. The purpose of this study was to assess the bioaccessibility of beryllium from bertrandite ore. Dissolution of bertrandite from two mine pits (Monitor and Blue Chalk) was evaluated for both the dermal and inhalation exposure pathways by determining bioaccessibility in artificial sweat (pH 5.3 and pH 6.5), airway lining fluid (SUF, pH 7.3), and alveolar macrophage phagolysosomal fluid (PSF, pH 4.5). Significantly more beryllium was released from Monitor pit ore than Blue Chalk pit ore in artificial sweat buffered to pH 5.3 (0.88 ± 0.01% vs. 0.36 ± 0.00%) and pH 6.5 (0.09 ± 0.00% vs. 0.03 ± 0.01%). Rates of beryllium released from the ores in artificial sweat were faster than previously measured for manufactured forms of beryllium (e.g., beryllium oxide), known to induce sensitization in mice. In SUF, levels of beryllium were below the analytical limit of detection. In PSF, beryllium dissolution was biphasic (initial rapid diffusion followed by latter slower surface reactions). During the latter phase, dissolution half-times were 1,400 to 2,000 days, and rate constants were ~7 × 10(-10) g/(cm(2)·day), indicating that bertrandite is persistent in the lung. These data indicate that it is prudent to control skin and inhalation exposures to bertrandite dusts.

Dynamic Postural-Stability Deficits After Cryotherapy to the Ankle Joint

PubMed Central

Fullam, Karl; Caulfield, Brian; Coughlan, Garrett F.; McGroarty, Mark; Delahunt, Eamonn

2015-01-01

Context  Decreased postural stability is a primary risk factor for lower limb musculoskeletal injuries. During athletic competitions, cryotherapy may be applied during short breaks in play or during half-time; however, its effects on postural stability remain unclear. Objective  To investigate the acute effects of a 15-minute ankle-joint cryotherapy application on dynamic postural stability. Design  Controlled laboratory study. Setting  University biomechanics laboratory. Patients or Other Participants  A total of 29 elite-level collegiate male field-sport athletes (age = 20.8 ± 1.12 years, height = 1.80 ± 0.06 m, mass = 81.89 ± 8.59 kg) participated. Intervention(s)  Participants were tested on the anterior (ANT), posterolateral (PL), and posteromedial (PM) reach directions of the Star Excursion Balance Test before and after a 15-minute ankle-joint cryotherapy application. Main Outcome Measure(s)  Normalized reach distances; sagittal-plane kinematics of the hip, knee, and ankle joints; and associated mean velocity of the center-of-pressure path during performance of the ANT, PL, and PM reach directions of the Star Excursion Balance Test. Results  We observed a decrease in reach-distance scores for the ANT, PL, and PM reach directions from precryotherapy to postcryotherapy (P < .05). No differences were observed in hip-, knee-, or ankle-joint sagittal-plane kinematics (P > .05). We noted a decrease in mean velocity of the center-of-pressure path from precryotherapy to postcryotherapy (P < .05) in all reach directions. Conclusions  Dynamic postural stability was adversely affected immediately after cryotherapy to the ankle joint. PMID:26285088

Albumin Binding Domain Fusing R/K-X-X-R/K Sequence for Enhancing Tumor Delivery of Doxorubicin.

PubMed

Liu, Liping; Zhang, Chun; Li, Zenglan; Wang, Chunyue; Bi, Jingxiu; Yin, Shuang; Wang, Qi; Yu, Rong; Liu, Yongdong; Su, Zhiguo

2017-11-06

For the purpose of improving the tumor delivery of doxorubicin (DOX), a kind of peptide-DOXO conjugate was designed and prepared, in which the peptide composed of an albumin-binding domain (ABD) and a tumor-specific internalizing sequence (RGDK or RPARPAR) was conjugated to a (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH). The doxorubicin uptake by lung cancer cell line of A549 evidenced that the conjugates are capable of being internalized through a tumor-specific sequence mediated manner, and the intracellular imaging of distribution in A549 cell demonstrated that the conjugated doxorubicin can be delivered to the cell nucleus. The A549 cell cytotoxicity of peptide-DOXO conjugates was presented with IC 50 values and shown in the range of about 9-11 μM. Pharmacokinetics study revealed that both conjugates exhibited nearly 5.5 times longer half-time than DOX, and about 4 times than DOXO-EMCH. The in vivo growth inhibitions of the two peptide-DOXO conjugates on BALB/c nude mice bearing A549 tumor (47.78% for ABD-RGDK-DOXO and 47.09% for ABD-RPARPAR-DOXO) were much stronger than that of doxorubicin and DOXO-EMCH (24.28% and 25.67% respectively) at a doxorubicin equivalent dose. Besides, the in vivo fluorescence imaging study confirmed that the peptide markedly increased the payload accumulation in tumor tissues and indicated that albumin binding domain fusing tumor-specific sequence effectively enhanced the tumor delivery of doxorubicin and thus improved its therapeutic potency.

Hot hands, cold feet? Investigating effects of interacting constraints on place kicking performance at the 2015 Rugby Union World Cup.

PubMed

Pocock, Chris; Bezodis, Neil E; Davids, Keith; North, Jamie S

2018-06-23

Place kicks in Rugby Union present valuable opportunities to score points outside the spatiotemporal dynamics of open play but are executed under varying performance constraints. We analysed effects of specific task constraints and relevant contextual factors on place kick performance in the 2015 Rugby Union World Cup. Data were collected from television broadcasts for each place kick. In addition to kick outcomes, contextual factors, including time of the kick in the match, score margin at the time of the kick, and outcome of the kicker's previous kick, were recorded. Effects of spatial task constraints were analysed for each kick, using distance (m) and angle (°) of the kick to the goalposts. A binomial logistic regression model revealed that distance from, and angle to, the goalposts were significant predictors of place kick outcome. Furthermore, the success percentage of kickers who missed their previous kick was 7% lower than those who scored their previous kick. Place kick success percentage in the 10 minutes before half-time was 8% lower than the mean tournament success percentage, which was 75% (95% CI 71-78%). The highest kick success percentage was recorded when scores were level (83%; 95% CI 72-91%). Our data highlighted how subtle changes in task constraints and contextual factors can influence performance outcomes in elite performers in international competition. Fluctuations in place kick success suggested that individual constraints, such as thoughts, emotions and fatigue, induced during competition, could interact with perceptions to influence emergent performance behaviours.

[Occupational carpal tunnel syndrome: 27 cases].

PubMed

Slimane, Neila Ben; Elleuch, Mohamed; Gharbi, Ezzedine; Babay, Habib; Hamdoun, Moncef

2010-09-01

Carpal tunnel syndrome is the most frequent of tunnel syndromes in the field of the professional sphere. It is related to repetitive movements of flexion-extension of the wrist and fingers or to a support on the heel of the hands. To determine the posts in a risk and to specify the modalities of guaranteed reimbursement of professional carpal tunnel syndrome. A retrospective and descriptive study of 27 medical files of employees indemnified for professional carpal tunnel syndrome registered in the medical control services of the social security office in charge of medical insurance of Tunis and Sousse during a period of 10 years (1995-2004). There were 24 women and 3 men with the average age of 40 years all occupying posts in a risk. Their average time of service is 15 years. Tow-thirds of them work in the clothing and textile industry. The attack is bilateral in 13 cases. Nightly acroparaesthesia rules the clinical rate (44.44% of cases). Motor disorders are noted in the quarter of cases. The electromyogram had confirmed diagnosis in all of cases. The previous state study put in evidence the antecedent of carpal tunnel syndrome in 5 cases and diabetes in one case. Twenty-one patients had profit of permanent partial incapacity with a rate varying from 3 to 25%. Five had got a transfer of working place and one stayed in the same post with a half-time work. The professional origin of carpal tunnel syndrome must be called up in front of an activity in a risk. The reparation is done according to picture 82 of occupational diseases.

Physiological and molecular characterization of an IRK-type inward rectifier K+ channel in a tumour mast cell line.

PubMed

Wischmeyer, E; Lentes, K U; Karschin, A

1995-04-01

The basophilic leucaemia cell line RBL-2H3 exhibits a robust inwardly rectifying potassium current, IKIR, which is likely to be modulated by G proteins. We examined the physiological and molecular properties of this KIR conductance to define the nature of the underlying channel species. The macroscopic conductance revealed characteristics typical of classical K+ inward rectifiers of the IRK type. Channel gating was rapid, first order (tau approximately 1 ms at -100 mV) and steeply voltage dependent. Both activation potential and slope conductance were dependent on extracellular K+ concentration ([K+]o) and inward rectification persisted in the absence of internal Mg2+. The current was susceptible to a concentration- and voltage-dependent block by extracellular Na+, Cs+ and Ba2+. Initial IKIR whole-cell amplitudes as well as current rundown were dependent on the presence of 1 mM internal ATP. Perfusion of intracellular guanosine 5'-Q-(3-thiotriphosphate) (GTP[gamma S]) suppressed IKIR with an average half-time of decline of approximately 400 s. It was demonstrated that the dominant IRK-type 25 pS conductance channel was indeed suppressed by 100 microM preloaded GTP[gamma S]. Reverse transcriptase-polymerase chain reactions (RT-PCR) with RBL cell poly(A)+ RNA identified a full length K+ inward rectifier with 94% base pair homology to the recently cloned mouse IRK1 channel. It is concluded that RBL cells express a classical voltage-dependent IRK-type K+ inward rectifier RBL-IRK1 which is negatively controlled by G proteins.

Alkylating derivative of oxotremorine interacts irreversibly with the muscarinic receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ehlert, F.J.; Jenden, D.J.; Ringdahl, B.

A 2-chloroethylamine derivative of oxotremorine was studied in pharmacological experiments and muscarinic receptor binding assays. The compound, N-(4-(2-chloroethylmethylamino)-2-butynyl)-2-pyrrolidone (BM 123), forms an aziridinium ion in aqueous solution at neutral pH that stimulates contractions of guinea pig ileum with a potency similar to that of oxotremorine. Following the initial stimulation, there is a long lasting period of lack of sensitivity of the guinea pig ileum to muscarinic agonists. BM 123 also produces muscarinic effects in vivo. When homogenates of the rat cerebral cortex were incubated with BM 123 and assayed subsequently in muscarinic receptor binding assays, a loss of binding capacitymore » for the muscarinic antagonist, (/sup 3/H)N-methylscopolamine ((/sup 3/H)NMS), was noted without a change in affinity. Similar observations were made in (/sup 3/H)1-3-quinuclidinyl benzilate ((/sup 3/H)-QNB) binding assays on the forebrains of mice that had been injected with BM 123 24 hr earlier. The loss in receptor capacity for both (/sup 3/H)NMS and (/sup 3/H)-QNB was prevented by atropine treatment. Kinetic studies of the interaction of BM 123 with homogenates of the rat cerebral cortex in vitro showed that the half-time for the loss of (/sup 3/H)-QNB binding sites increased from 10 to 45 min as the concentration of BM 123 decreased from 10 to 1 ..mu..M. In contrast to the aziridinium ion, the parent 2-chloroethylamine compound and the alcoholic hydrolysis product were largely devoid of pharmacological and binding activity.« less

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial.

PubMed

Rigby-Jones, Ann E; Sneyd, J Robert; Vijn, Peter; Boen, Patrick; Cross, Maurice

2010-06-29

Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics.

Thylakoid membrane protein topography: transmembrane orientation of the chloroplast cytochrome b-559 psbE gene product.

PubMed

Tae, G S; Black, M T; Cramer, W A; Vallon, O; Bogorad, L

1988-12-27

Protease accessibility and antibody to a COOH-terminal peptide were used as probes for the in situ topography of the Mr 10,000 psbE gene product (alpha subunit) of the chloroplast cytochrome b-559. Exposure of thylakoid membranes to trypsin or Staphylococcus aureus V8 protease cleaved the alpha subunit to a slightly smaller polypeptide (delta Mr approximately -1000) as detected on Western blots, without loss of reactivity to COOH-terminal antibody. The disappearance of the parent Mr 10,000 polypeptide from thylakoids in the presence of trypsin correlated with the appearance of the smaller polypeptide with delta Mr = -750, the conversion having a half-time of approximately 15 min. Exposure of inside-out vesicles to trypsin resulted in almost complete loss of reactivity to the antibody, showing that the COOH terminus is exposed on the lumenal side of the membrane. Removal of the extrinsic polypeptides of the oxygen-evolving complex resulted in an increase of the accessibility of the alpha subunit to trypsin. These data establish that the alpha subunit of cytochrome b-559 crosses the membrane once, as predicted from its single, 26-residue, hydrophobic domain. The NH2 terminus of the alpha polypeptide is on the stromal side of the membrane, where it is accessible, most likely at Arg-7 or Glu-6/Asp-11, to trypsin or V8 protease, respectively. As a consequence of this orientation, the single histidine residue in the alpha subunit is located on the stromal side of the hydrophobic domain.(ABSTRACT TRUNCATED AT 250 WORDS)

Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung

PubMed Central

Numata, Mari; Grinkova, Yelena V; Mitchell, James R; Chu, Hong Wei; Sligar, Stephen G; Voelker, Dennis R

2013-01-01

There is increasing interest in the application of nanotechnology to solve the difficult problem of therapeutic administration of pharmaceuticals. Nanodiscs, composed of a stable discoidal lipid bilayer encircled by an amphipathic membrane scaffold protein that is an engineered variant of the human Apo A-I constituent of high-density lipoproteins, have been a successful platform for providing a controlled lipid composition in particles that are especially useful for investigating membrane protein structure and function. In this communication, we demonstrate that nanodiscs are effective in suppressing respiratory syncytial viral (RSV) infection both in vitro and in vivo when self-assembled with the minor pulmonary surfactant phospholipid palmitoyloleoylphosphatidylglycerol (POPG). Preparations of nanodiscs containing POPG (nPOPG) antagonized interleukin-8 production from Beas2B epithelial cells challenged by RSV infection, with an IC50 of 19.3 μg/mL. In quantitative in vitro plaque assays, nPOPG reduced RSV infection by 93%. In vivo, nPOPG suppressed inflammatory cell infiltration into the lung, as well as IFN-γ production in response to RSV challenge. nPOPG also completely suppressed the histopathological changes in lung tissue elicited by RSV and reduced the amount of virus recovered from lung tissue by 96%. The turnover rate of nPOPG was estimated to have a halftime of 60–120 minutes (m), based upon quantification of the recovery of the human Apo A-I constituent. From these data, we conclude that nPOPG is a potent antagonist of RSV infection and its inflammatory sequelae both in vitro and in vivo. PMID:23717040

Vitamin K2 (menaquinone) biosynthesis in Escherichia coli: evidence for the presence of an essential histidine residue in o-succinylbenzoyl coenzyme A synthetase.

PubMed Central

Bhattacharyya, D K; Kwon, O; Meganathan, R

1997-01-01

o-Succinylbenzoyl coenzyme A (OSB-CoA) synthetase, when treated with diethylpyrocarbonate (DEP), showed a time-dependent loss of enzyme activity. The inactivation follows pseudo-first-order kinetics with a second-order rate constant of 9.2 x 10(-4) +/- 1.4 x 10(-4) microM(-1) min(-1). The difference spectrum of the modified enzyme versus the native enzyme showed an increase in A242 that is characteristic of N-carbethoxyhistidine and was reversed by treatment with hydroxylamine. Inactivation due to nonspecific secondary structural changes in the protein and modification of tyrosine, lysine, or cysteine residues was ruled out. Kinetics of enzyme inactivation and the stoichiometry of histidine modification indicate that of the eight histidine residues modified per subunit of the enzyme, a single residue is responsible for the enzyme activity. A plot of the log reciprocal of the half-time of inactivation against the log DEP concentration further suggests that one histidine residue is involved in the catalysis. Further, the enzyme was partially protected from inactivation by either o-succinylbenzoic acid (OSB), ATP, or ATP plus Mg2+ while inactivation was completely prevented by the presence of the combination of OSB, ATP, and Mg2+. Thus, it appears that a histidine residue located at or near the active site of the enzyme is essential for activity. When His341 present in the previously identified ATP binding motif was mutated to Ala, the enzyme lost 65% of its activity and the Km for ATP increased 5.4-fold. Thus, His341 of OSB-CoA synthetase plays an important role in catalysis since it is probably involved in the binding of ATP to the enzyme. PMID:9324253

Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibers and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609.

PubMed

Grunnet, Louise G; Brøns, Charlotte; Jacobsen, Stine; Nilsson, Emma; Astrup, Arne; Hansen, Torben; Pedersen, Oluf; Poulsen, Pernille; Quistorff, Bjørn; Vaag, Allan

2009-02-01

Recent studies identified the rs9939609 A-allele of the FTO (fat mass and obesity associated) gene as being associated with obesity and type 2 diabetes. We studied the role of the A-allele in the regulation of peripheral organ functions involved in the pathogenesis of obesity and type 2 diabetes. Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an iv glucose tolerance test, 31phosphorous magnetic resonance spectroscopy, and 24-h whole body metabolism was measured in a respiratory chamber. The FTO rs9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance, and shorter recovery half-times of phosphocreatine and inorganic phosphate after exercise in a primarily type I muscle. These relationships--except for fasting insulin--remained significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sensitivity, insulin secretion, 24-h energy expenditure, or glucose and fat oxidation. The FTO genotype did not influence the mRNA expression of FTO or a set of key nuclear or mitochondrially encoded genes in skeletal muscle during rest. Increased energy efficiency--and potentially increased mitochondrial coupling--as suggested by faster recovery rates of phosphocreatine and inorganic phosphate in oxidative muscle fibers may contribute to the increased risk of obesity and type 2 diabetes in homozygous carriers of the FTO A-risk allele. Hepatic insulin resistance may represent the key metabolic defect responsible for mild elevations of fasting blood glucose associated with the FTO phenotype.

Could some aviation deep vein thrombosis be a form of decompression sickness?

PubMed

Buzzacott, Peter; Mollerlokken, Andreas

2016-10-01

Aviation deep vein thrombosis is a challenge poorly understood in modern aviation. The aim of the present project was to determine if cabin decompression might favor formation of vascular bubbles in commercial air travelers. Thirty commercial flights were taken. Cabin pressure was noted at take-off and at every minute following, until the pressure stabilized. These time-pressure profiles were imported into the statistics program R and analyzed using the package SCUBA. Greatest pressure differentials between tissues and cabin pressures were estimated for 20, 40, 60, 80 and 120 min half-time compartments. Time to decompress ranged from 11 to 47 min. The greatest drop in cabin pressure was from 1022 to 776 mBar, equivalent to a saturated diver ascending from 2.46 msw depth. Mean pressure drop in flights >2 h duration was 193 mBar, while mean pressure drop in flights <2 h was 165 mBar. The greatest drop in pressure over 1 min was 28 mBar. Over 30 commercial flights it was found that the drop in cabin pressure was commensurate with that found to cause bubbles in man. Both the US Navy and the Royal Navy mandate far slower decompression from states of saturation, being 1.7 and 1.9 mBar/min respectively. The median overall rate of decompression found in this study was 8.5 mBar/min, five times the rate prescribed for USN saturation divers. The tissues associated with hypobaric bubble formation are likely slower than those associated with bounce diving, with 60 min a potentially useful index.

Amyloid-beta aggregates formed at polar-nonpolar interfaces differ from amyloid-beta protofibrils produced in aqueous buffers.

PubMed

Nichols, Michael R; Moss, Melissa A; Reed, Dana Kim; Hoh, Jan H; Rosenberry, Terrone L

2005-07-01

The deposition of aggregated amyloid-beta (Abeta) peptides in the brain as senile plaques is a pathological hallmark of Alzheimer's disease (AD). Several lines of evidence indicate that fibrillar and, in particular, soluble aggregates of these 40- and 42-residue peptides are important in the etiology of AD. Recent studies also stress that amyloid aggregates are polymorphic and that a single polypeptide can fold into multiple amyloid conformations. Here we review our recent reports that Abeta(1-40) in vitro can form soluble aggregates with predominant beta-structures that differ in stability and morphology. One class of aggregates involved soluble Abeta protofibrils, prepared by vigorous overnight agitation of monomeric Abeta(1-40) in low ionic strength buffers. These aggregates were quite stable and disaggregated to only a limited extent on dilution. A second class of soluble Abeta aggregates was generated at polar-nonpolar interfaces. Aggregation in a two-phase system of buffer over chloroform occurred more rapidly than in buffer alone. In buffered 2% hexafluoroisopropanol (HFIP), microdroplets of HFIP were formed and the half-time for aggregation was less than 10 minutes. Like Abeta protofibrils, these interfacial aggregates showed increased thioflavin T fluorescence and were rich in beta-structure by circular dichroism. However, electron microscopy and atomic force microscopy revealed very different morphologies. The HFIP aggregates formed initial globular clusters that progressed over several days to soluble fibrous aggregates. When diluted out of HFIP these aggregates initially were very unstable and disaggregated completely within 2 minutes. However, their stability increased as they progressed to fibers. It is important to determine whether similar interfacial Abeta aggregates are produced in vivo.

Physiological studies in the South American camelid llama (Lama guanicoe f. d. glama). I. Body water spaces and water turnover.

PubMed

Marcilese, N A; Ghezzi, M D; Aba, M A; Alzola, R A; Solana, H; Valsecchi, R M

1994-01-01

Body water (BW) and extracellular water (ECW), were determined with tritiated water (THO) and 82Br injected into the vein, to 8 mature animals of both sexes during the winter season. The biological half-time of THO (T1/2 THO) and the daily water turnover (WT) were measured and the intracellular water (ICW) calculated. The studies with THO were repeated in the same animals and in 2 lactating females in spring and summer. Two calves were also studied during spring. The values obtained in winter were: BW 659 +/- 12 ml/kg; T1/2 THO 9.2 +/- 1 day; WT per 24 h 50 +/- 3 ml/kg or 116 +/- 5 ml/kg 82 and 163 +/- 9 ml per 1 of BW82; ECW 215 +/- 8 ml/kg or 32.5 +/- 3% BW; ICW 447 +/- 12 ml/kg or 67.7 +/- 4% BW. The results of the spring's studies showed a significant increase in the values of WT. In summer a further increment of this parameters was observed when expressed as ml/kg body solids. This differences were remarkable in those in lactation. The proportion of water in the body was significantly higher during summer in all animals. BW in lactating animals during summer was 783 +/- 9 ml/kg and in the other animals 718 +/- 18; T1/2 THO values were 3.3 +/- .-06 and 4.5 +/- .4 day, respectively. WT was 396 +/- 9 ml/kg.82 or 484 +/- 8 ml/l BW82 in the lactating animals and 260 +/- 9 ml/kg 82 or 341 +/- 12 ml/l BW82 in the other animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the effects of toluene inhalation on alveolar epithelial permeability by 99mTc-DTPA inhalation scintigraphy in automobile painters.

PubMed

Cerci, Sevim Sureyya; Ozturk, Onder; Sutcu, Recep; Ozbek, Feride Meltem; Baydar, Cetin Lutfi; Yildiz, Mustafa; Akkaya, Ahmet; Delibas, Namk

2008-01-01

The main component of paint thinner used in industry is toluene diisocyanate (TDI) which can cause occupational asthma in 5-10% of exposed workers. To investigate the effect of TDI on 99mTc clearance rate of alveolar epithelium and on pulmonary function tests (PFT) in automobile painters, and to determine the relationship between 99mTc-DTPA radioaerosol lung scintigraphy and serum levels of antioxidant enzymes and metalloproteinases (MMPs) of automobile painters. Twenty-eight automobile painters and 13 control subjects were included in the study. 99mTc-DTPA aerosol inhalation scintigraphy and PFT were administered to all subjects. Clearance half-time (T1/2) and penetration index (PI) on the first-minute image after 99mTc-DTPA scintigraphy were calculated. Blood levels of MDA, antioxidant enzymes and metalloproteinases were measured. The mean T1/2 values of automobile painters were longer in both smoker and non-smoker subjects, but the difference was not significant (P>0.05). Although the PFT values decreased in automobile painters, there was no significant difference between each group. Any correlation between spirometric measurements and T1/2 or PI values in non-smoking automobile painters was not detected. Negative correlation among mean T1/2 value and FVC% and FEV1% in smoking automobile painters, and positive correlation between mean T1/2 value and MMP-9, GSH-Px levels in non-smoking automobile painters were detected. Our results suggested that the clearance of 99mTc-DTPA from the lungs of automobile painters was slower than in the control group, but the difference is not statistically significant. This data also supports the observation that TDI occasionally stimulates bronchial changes rather than alveolar changes in automobile painters.

One-year results of a prospective randomized, evaluator-blinded, multicenter study comparing TVT and TVT Secur.

PubMed

Andrada Hamer, Maria; Larsson, Per-Göran; Teleman, Pia; Bergqvist, Christina Eten; Persson, Jan

2013-02-01

The aim of this prospective randomized multicenter study was to compare retropubic tension-free vaginal tape (TVT) with TVT Secur in terms of efficacy and safety. We set out to enrol 280 stress urinary incontinent (SUI) women with a half-time interim analysis of short-term cure and adverse events. The short-term results have previously been published. Of the 133 randomized women, 125 underwent surgery, and 121 (TVT n = 61, TVT Secur n = 60) were available for follow-up 1 year postsurgery. No significant differences were found between groups regarding demographics or incontinence grade. One year after surgery, both subjective and objective cure rates were significantly lower for TVT Secur than for TVT (subjective cure: TVT 98 %, TVT Secur 80 %, p = 0.03; objective cure: TVT 94 %, TVT Secur 71 % for cough test, p = 0.01; TVT 76 %, TVT Secur 58 % for pad test, p = 0.05 ). Three major complications occurred in the TVT Secur group: one tape erosion into the urethra, one tape inadvertently placed into the bladder, and one immediate postoperative bleeding due to injury to the corona mortis. No major complications occurred in the TVT group. No significant differences were found between groups regarding peroperative bleeding, hospital stay, urge symptoms, residual urinary volume, subjective bladder emptying problems, postoperative urinary tract infections, and minor complications. The TVT Secur group used more antimuscarine medication after surgery than the TVT group (p = 0.03). Median time for surgery was 13 and 22 min for TVT Secur and TVT, respectively (p < 0.0001). The TVT Secur procedure had significantly inferior subjective and objective cure rates compared with the retropubic TVT procedure. Three serious adverse events occurred in the TVT Secur group. We therefore discourage further use of TVT Secur.

Prolonged nerve block by microencapsulated bupivacaine prevents acute postoperative pain in rats.

PubMed

Ohri, Rachit; Blaskovich, Phillip; Wang, Jeffrey Chi-Fei; Pham, Lan; Nichols, Gary; Hildebrand, William; Costa, Daniel; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary

2012-01-01

To minimize acute postoperative pain, a new formulation of slowly released bupivacaine was developed. Bupivacaine was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and characterized for physicochemical properties and bupivacaine release kinetics. This formulation was injected around the rat sciatic nerve to produce an antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine slow-release formulation was placed at the ipsilateral sciatic nerve and compared with the hyperalgesia that developed with various controls. Bupivacaine was released in vitro at a relatively constant rate over a period of ≈ 72 to 96 hours. Complete antinociception, shown as no response to toe pinch, lasted for 23 ± 7 hours, with a half-recovery time of 42 ± 8 hours after sciatic nerve injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine. Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete antinociception for less than 2 hours and recovery half-times of 2 hours. Postincisional mechanical hyperalgesia, shown by increased withdrawal responses to von Frey filaments, was absent for 24 hours and was lower than control for 96 hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours. Corresponding to its far greater functional blocking time, the microsphere-bupivacaine formulation was able to significantly reduce postoperative pain below control levels for up to 4 days. These findings of several days of postoperative pain relief, for an injectable formulation containing a single active agent, present an improved and potentially promising therapy to prevent acute pain after surgery.

Characterization of long-term extension of isolated cell walls from growing cucumber hypocotyls

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

1989-01-01

Walls from frozen-thawed cucumber (Cucumis sativus L.) hypocotyls extend for many hours when placed in tension under acidic conditions. This study examined whether such "creep" is a purely physical process dependent on wall viscoelasticity alone or whether enzymatic activities are needed to maintain wall extension. Chemical denaturants inhibited wall creep, some acting reversibly and others irreversibly. Brief (15 s) boiling in water irreversibly inhibited creep, as did pre-incubation with proteases. Creep exhibited a high Q10 (3.8) between 20 degrees and 30 degrees C, with slow inactivation at higher temperatures, whereas the viscous flow of pectin solutions exhibited a much lower Q10 (1.35). On the basis of its temperature sensitivity, involvement of pectic gel-sol transitions was judged to be of little importance in creep. Pre-incubation of walls in neutral pH irreversibly inactivated their ability to creep, with a half-time of about 40 min. At 1 mM, Cu2+, Hg2+ and Al3+ were strongly inhibitory whereas most other cations, including Ca2+, had little effect. Sulfhydryl-reducing agents strongly stimulated creep, apparently by stabilizing wall enzyme(s). The physical effects of these treatments on polymer interactions were examined by Instron and stress-relaxation analyses. Some treatments, such as pH and Cu2+, had significant effects on wall viscoelasticity, but others had little or no apparent effect, thus implicating an enzymatic creep mechanism. The results indicate that creep depends on relatively rugged enzymes that are firmly attached to or entangled in the wall. The sensitivity of creep to SH-reducing agents indicates that thiol reduction of wall enzymes might provide a control mechanism for endogenous cell growth.

Dynamics of Photosystem II and Its Light Harvesting System in Response to Light Changes in the Halotolerant Alga Dunaliella salina1

PubMed Central

Pick, Uri; Gounaris, Kleoniki; Barber, James

1987-01-01

A photosystem two (PSII) core complex consisting of five major polypeptides (47, 40, 32, 30, and 10 kilodaltons) and a light harvesting chlorophyll a/b complex (LHC-2) have been isolated from the halotolerant alga Dunaliella salina. The chlorophyll and polypeptide composition of both complexes were compared in illuminated and dark-adapted cultures. Dark adaptation is accompanied by a decrease in the chlorophyll a to chlorophyll b (Chl a/Chl b) ratio of intact thylakoids without any change in total chlorophyll. These changes occur with a half-time of 3 hours and are reversed upon reillumination. Analyses of PSII enriched membrane fragments suggest that the decrease in the Chl a/Chl b is due partly to an increase in the Chl b content of LHC-2 and partly to changes in the relative levels of the two complexes. Apparently during dark adaptation there is: (a) a net synthesis of chlorophyll b, (b) removal of PSII core complexes resulting in a 2-fold drop in the PSII cores to LHC-2 chlorophyll ratio. These changes should dramatically increase the light harvesting capacity of the remaining PSII reaction centers. Presumably this adjustment of antenna size and composition is a physiological mechanism necessary for responding to shade conditions. Also detected, using 32P, are light-induced phosphorylation of the LHC-2 (consistent with the ability to undergo State transitions) and of the 40 and 30 kilodalton subunits of the PSII core complex. These observations indicate that additional mechanisms may also exist to help optimize the interception of quanta during rapid changes in illumination conditions. Images Fig. 4 PMID:16665656

A Combination of Amino Acids and Caffeine Enhances Sprint Running Capacity in a Hot, Hypoxic Environment.

PubMed

Eaton, Tom R; Potter, Aaron; Billaut, François; Panchuk, Derek; Pyne, David B; Gore, Christopher J; Chen, Ting-Ting; McQuade, Leon; Stepto, Nigel K

2016-02-01

Heat and hypoxia exacerbate central nervous system (CNS) fatigue. We therefore investigated whether essential amino acid (EAA) and caffeine ingestion attenuates CNS fatigue in a simulated team sport-specific running protocol in a hot, hypoxic environment. Subelite male team sport athletes (n = 8) performed a repeat sprint running protocol on a nonmotorized treadmill in an extreme environment on 4 separate occasions. Participants ingested one of four supplements: a double placebo, 3 mg.kg-1 body mass of caffeine + placebo, 2 x 7 g EAA (Musashi Create)+placebo, or caffeine + EAA before each exercise session using a randomized, double-blind crossover design. Electromyography (EMG) activity and quadriceps evoked responses to magnetic stimulation were assessed from the dominant leg at preexercise, halftime, and postexercise. Central activation ratio (CAR) was used to quantify completeness of quadriceps activation. Oxygenation of the prefrontal cortex was measured via near-infrared spectroscopy. Mean sprint work was higher (M = 174 J, 95% CI [23, 324], p < .05, d = 0.30; effect size, likely beneficial) in the caffeine + EAA condition versus EAAs alone. The decline in EMG activity was less (M = 13%, 95% CI [0, 26]; p < .01, d = 0.58, likely beneficial) in caffeine + EAA versus EAA alone. Similarly, the pre- to postexercise decrement in CAR was significantly less (M = -2.7%, 95% CI [0.4, 5.4]; p < .05, d = 0.50, likely beneficial) when caffeine + EAA were ingested compared with placebo. Cerebral oxygenation was lower (M = -5.6%, 95% CI [1.0, 10.1]; p < .01, d = 0.60, very likely beneficial) in the caffeine + EAA condition compared with LNAA alone. Co-ingestion of caffeine and EAA appears to maintain muscle activation and central drive, with a small improvement in running performance.

[Promotion effects of vitamin B12 on the degradation of 2, 4, 4'-trichlorobiphenyl by Nostoc PD-2].

PubMed

Liu, Jia-Yu; Xiao, Wen-Feng; Lu, Li-Ping; Zhang, Hang-Jun

2014-08-01

Polychlorinated biphenyls are typical persistent chlorinated organic compounds in the environment. Bioremediation of PCB-contaminated environment has become one of the hot issues. In this study, vitamin B12 (VB12) and chlorine-free culture medium were applied to study the effects of VB12 on the degradation of 2,4,4'-trichlorobiphenyl (PCB28) by Nostoc PD-2 and the gene expression during the PCB-degradation process. Results showed that addition of different concentrations of vitamin B12 could improve the PCB-biodegradation rates by Nostoc PD-2. Compared with the control group, the 7-day degradation rate in 10 microg x L(-1), 100 microg x L(-1), and 1 000 microg x L(-1) VB12-treated groups increased by 11.0%, 19.7%, and 21.9% , respectively. The degradation half-time decreased from 5.53 days (treated with 10 microg x L(-1) VB12) to 3.08 days (treated with 100 microg x L(-1) VB12). The expression of cytochrome b6f complex iron-sulfur protein gene and dioxygenase gene showed significant correlation with PCB28-degradation by Nostoc PD-2. While the expression of iron-sulfur protein gene showed more significant correlation with PCB28-degradation. Results in this study indicated that adding VB12 could promote PCB28-degradation by Nostoc PD-2. Moreover, VB12 addition improved the PCB-degradation activity of Nostoc PD-2 at the gene level. The above conclusions could provide a new choice for developing efficient bioremediation technology for PCB-contaminated environment and a new insight into the PCB-biodegradation mechanism by Nostoc PD-2.

Processing of N-linked oligosaccharide depends on its location in the anion exchanger, AE1, membrane glycoprotein.

PubMed

Li, J; Quilty, J; Popov, M; Reithmeier, R A

2000-07-01

The human erythrocyte anion exchanger (AE)1 (Band 3) contains a single complex N-linked oligosaccharide that is attached to Asn(642) in the fourth extracellular loop of this polytopic membrane protein, while other isoforms (AE2, AE3 and trout AE1) are N-glycosylated on the preceding extracellular loop. Human AE1 expressed in transfected human embryonic kidney (HEK)-293 or COS-7 cells contained a high-mannose oligosaccharide. The lack of oligosaccharide processing was not due to retention of AE1 in the endoplasmic reticulum since biotinylation assays showed that approx. 30% of the protein was expressed at the cell surface. Moving the N-glycosylation site to the preceding extracellular loop in an AE1 glycosylation mutant (N555) resulted in processing of the oligosaccharide and production of a complex form of AE1. A double N-glycosylation mutant (N555/N642) contained both a high-mannose and a complex oligosaccharide chain. The complex form of the N555 mutant could be biotinylated showing that this form of the glycoprotein was at the cell surface. Pulse-chase experiments showed that the N555 mutant was efficiently converted from a high-mannose to a complex oligosaccharide with a half-time of approx. 4 h, which reflected the time course of trafficking of AE1 from the endoplasmic reticulum to the plasma membrane. The turnover of the complex form of the N555 mutant occurred with a half-life of approx. 15 h. The results show that the oligosaccharide attached to the endogenous site in extracellular loop 4 in human AE1 is not processed in HEK-293 or COS-7 cells, while the oligosaccharide attached to the preceding loop is converted into the complex form.

Biosynthesis and N-glycosylation of human interferon-gamma. Asn25 and Asn97 differ markedly in how efficiently they are glycosylated and in their oligosaccharide composition.

PubMed

Sareneva, T; Mørtz, E; Tölö, H; Roepstorff, P; Julkunen, I

1996-12-01

Interferon-gamma (IFN-gamma) is a secretory glycoprotein produced by T cells in response to antigenic or mitogenic stimuli. We studied the kinetics of the synthesis, N-glycosylation, and secretion of IFN-gamma in human CD8+ T lymphocytes stimulated via T-cell receptor. Highly elevated IFN-gamma mRNA levels were found as early as 1 h after stimulation. Maximal IFN-gamma protein synthesis was observed 2-4 h after induction and appeared to correlate to steady-state IFN-gamma mRNA levels. As analyzed by pulse/chase experiments, the secretion of IFN-gamma from T cells was very rapid, the secretion half-time being approximately 20-25 min. Inhibition of N-glycosylation by tunicamycin dramatically reduced the expression of IFN-gamma, but did not block its secretion. Natural IFN-gamma is heterogeneously glycosylated and doubly, singly, and unglycosylated forms exist. Experiments performed in a cell-free translation/glycosylation system with mutated IFN-gamma constructs lacking either one of the potential glycosylation sites suggested that Asn25 is more efficiently glycosylated than Asn97. Site-specific oligosaccharide analysis of natural IFN-gamma by glycosidase treatment followed by matrix-assisted-laser-desorption-ionization mass spectrometry revealed considerable variation in the carbohydrate structures, with more than 30 different forms. The glycans at Asn25 consisted of fucosylated, mainly complex-type oligosaccharides, whereas the glycans at Asn97 were more heterogeneous, with hybrid and high-mannose structures. Our results emphasize the essential role of N-linked glycans in the biology of IFN-gamma and show that there is a considerable heterogeneity in the individual sugar chains of this important human cytokine.

Transport across the blood-brain barrier of pluronic leptin.

PubMed

Price, Tulin O; Farr, Susan A; Yi, Xiang; Vinogradov, Serguei; Batrakova, Elena; Banks, William A; Kabanov, Alexander V

2010-04-01

Leptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity. Chemical modification of polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) is a promising technology to improve efficiency of delivery of polypeptides to the brain. In the present study, we determined the effects of Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance, stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when injected intracerebroventricularly after overnight food deprivation and 125I-leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain unidirectional influx rate (K(i)) = 0.272 +/- 0.037 microl/g x min] by a nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was administered via tail vein in normal body weight mice [0-30 min, p < 0.0005; 0-2 h, p < 0.001]. These studies show that the structure based Pluronic modification of leptin increased metabolic stability, reduced food intake, and allowed BBB penetration by a mechanism-independent BBB leptin transporter.

The Impact of Individual In Vivo Repair of DNA Double-Strand Breaks on Oral Mucositis in Adjuvant Radiotherapy of Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fleckenstein, Jochen, E-mail: rajfle@uks.eu; Kuehne, Martin; Seegmueller, Katharina

2011-12-01

Purpose: To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT). Patients and Methods: Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60-66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, {gamma}-H2AX foci in blood lymphocytes were quantified before and 0.5more » h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair. Results: Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade {>=} 3 mucositis (n = 18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade {<=}2 mucositis (n = 13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis. Conclusions: Evaluation of in vivo DSB repair by determination of {gamma}-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.« less

Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy?

PubMed Central

Hughes, J R; Bowes, S G; Leeman, A L; O'Neill, C J; Deshmukh, A A; Nicholson, P W; Dobbs, S M; Dobbs, R J

1990-01-01

1. Normally during walking, the heel strikes the ground before the forefoot. Abnormalities of foot strike in idiopathic Parkinson's disease may be amenable to therapy: objective measurements may reveal response which is not clinically apparent. Occult changes in foot strike leading to instability may parallel the normal, age-related loss of striatal dopamine. 2. The nature of foot strike was studied using pedobarography in 160 healthy volunteers, aged 15 to 91 years. Although 16% of strikes were made simultaneously by heel and forefoot, there were no instances of the forefoot preceding the heel. No significant effect of age on an index of normality of foot strikes was detected (P greater than 0.3). 3. The effect on foot strike of substituting placebo for a morning dose of a levodopa/carbidopa combination was studied in a double-blind, cross-over trial in 14 patients, aged 64 to 88 years, with no overt fluctuations in control of their idiopathic Parkinson's disease in relation to dosing. On placebo treatment there was a highly significant (P = 0.004) reduction in the number of more normal strikes, i.e. heel strikes plus simultaneous heel and forefoot strikes. The effect appeared unrelated to the corresponding difference between active and placebo treatments in plasma concentration of levodopa or a metabolite of long half-time, 3-O-methyldopa (3OMD). However, it correlated negatively (P less than 0.05) with the mean of the 3OMD concentrations. 4. It appears that some abnormalities of foot strike due to Parkinson's disease are reversible. Employing test conditions, designed to provoke abnormalities of foot strike, might be useful in screening for pre-clinical Parkinson's disease. PMID:2306409

Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage—a modelling study

NASA Astrophysics Data System (ADS)

Røthe Arnesen, Marius; Paulsen Hellebust, Taran; Malinen, Eirik

2017-03-01

Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

Effects of pre-cooling procedures on intermittent-sprint exercise performance in warm conditions.

PubMed

Duffield, Rob; Marino, Frank E

2007-08-01

The aim of this study was to determine whether pre-cooling procedures improve both maximal sprint and sub-maximal work during intermittent-sprint exercise. Nine male rugby players performed a familiarisation session and three testing sessions of a 2 x 30-min intermittent sprint protocol, which consisted of a 15-m sprint every min separated by free-paced hard-running, jogging and walking in 32 degrees C and 30% humidity. The three sessions included a control condition, Ice-vest condition and Ice-bath/Ice-vest condition, with respective cooling interventions imposed for 15-min pre-exercise and 10-min at half-time. Performance measures of sprint time and % decline and distance covered during sub-maximal exercise were recorded, while physiological measures of core temperature (T (core)), mean skin temperature (T (skin)), heart rate, heat storage, nude mass, rate of perceived exertion, rate of thermal comfort and capillary blood measures of lactate [La(-)], pH, Sodium (Na(+)) and Potassium (K(+)) were recorded. Results for exercise performance indicated no significant differences between conditions for the time or % decline in 15-m sprint efforts or the distance covered during sub-maximal work bouts; however, large effect size data indicated a greater distance covered during hard running following Ice-bath cooling. Further, lowered T (core), T (skin), heart rate, sweat loss and thermal comfort following Ice-bath cooling than Ice-vest or Control conditions were present, with no differences present in capillary blood measures of [La(-)], pH, K(+) or Na(+). As such, the ergogenic benefits of effective pre-cooling procedures in warm conditions for team-sports may be predominantly evident during sub-maximal bouts of exercise.

Inhibition of Neuronal Voltage-Gated Sodium Channels by Brilliant Blue G

PubMed Central

Jo, Sooyeon

2011-01-01

Brilliant blue G (BBG), best known as an antagonist of P2X7 receptors, was found to inhibit voltage-gated sodium currents in N1E-115 neuroblastoma cells. Sodium currents elicited from a holding potential of −60 mV were blocked with an IC50 of 2 μM. Block was enhanced in a use-dependent manner at higher stimulation rates. The voltage-dependence of inactivation was shifted in the hyperpolarizing direction, and recovery from inactivation was slowed by BBG. The most dramatic effect of BBG was to slow recovery from inactivation after long depolarizations, with 3 μM BBG increasing half-time for recovery (measured at −120 mV) from 24 to 854 ms after a 10-s step to 0 mV. These results were mimicked by a kinetic model in which BBG binds weakly to resting channels (Kd = 170 μM) but tightly to fast-inactivated channels (Kd = 5 μM) and even more tightly (Kd = 0.2 μM) to slow-inactivated channels. In contrast to BBG, the structurally related food-coloring dye Brilliant Blue FCF had very little effect at concentrations up to 30 μM. These results show that BBG inhibits voltage-gated sodium channels at micromolar concentrations. Although BBG inhibition of sodium channels is less potent than inhibition of P2X7 receptors, there may be significant inhibition of sodium channels at BBG concentrations achieved in spinal cord or brain during experimental treatment of spinal cord injury or Huntington's disease. Considered as a sodium channel blocker, BBG is remarkably potent, acting with more than 10-fold greater potency than lacosamide, another blocker thought to bind to slow-inactivated channels. PMID:21536754

RSI: oxygen consumption, blood flow, and reoxygenation in patients suffering RSI measured by noninvasive optical spectroscopy

NASA Astrophysics Data System (ADS)

Thijssen, Dick H. J.; van Uden, Caro J. T.; Krijgsman, Hans; Colier, Willy N. J. M.

2003-07-01

Background: Repetitive Strain Injury (RSI) is a major problem in nowadays health care and creates high financial costs and personal distress. Average prevalence rates in the Netherlands vary from 20-40% of the working population. Insight into the patho-physiological mechanism of RSI is important in order to establish adequate treatment and prevention programs. Objective: The aim of this study was to gain insight in muscle oxygen consumption (mVO2), blood flow (BF), and reoxygenation (ReOx) in the forearm of computer workers with stage III Repetitive Strain Injury (RSI). Method: We have used continuous wave infrared spectroscopy (NIRS) to measure these variables. Measurements were conducted on the extensor and flexor muscle in both arms as well in RSI-patients (n=10) as in control subjects (n=21). A protocol of increased isometric repetitive contraction in a handgrip ergonometer was used with increasing levels of strength. Results: mVO2 in the extensor muscle in RSI-subjects (dominant side) was increased compared to control subjects and compared to the non-dominant side (p<0.05). ReOx was not increased in RSI (dominant side-extensor muscle). However, there was a tendency towards statistical significance (p=0.065). BF in rest was equal in both groups, however after exercise it tended to be increased. Half-time recovery (T ») was measured during only one part of the protocol and it was significantly increased (p<0.05). Conclusion: mVO2 in RSI is impaired. BF and ReOx did not show difference between both groups. Future research should aim at a microvascular dysfunction in RSI.

Gastric emptying of solids and liquids in obesity.

PubMed

Glasbrenner, B; Pieramico, O; Brecht-Krauss, D; Baur, M; Malfertheiner, P

1993-07-01

The purpose of this study was to determine whether obese patients have different rates of solid and liquid gastric emptying compared to healthy controls. Twenty-four obese patients (7 males, 17 females) were investigated prior to dietary restriction. The patients had a weight excess above ideal weight ranging from 25% to 216% (mean weight 118.1 +/- 6.5 kg). The control group consisted of 8 healthy subjects (4 males, 4 females), within 10% of the ideal weight. The solid phase of the test meal consisted of 40 g bread, 30 g ham, 10 g margarine, and two scrambled eggs labeled with 99mTc. For the liquid phase, 200 ml orange juice was labeled with 201Tl. Three-minute counts of both tracers were taken for 106 min using a large field-of-view gamma camera. In obese patients, a significantly shortened lag phase for the emptying of solids was observed (27.0 +/- 3.3 versus 38.4 +/- 4.1 min; P < 0.05). Half-emptying time (105.9 +/- 6.7 versus 100.7 +/- 5.7 min), emptying rate (0.60 +/- 0.04 versus 0.71 +/- 0.07%/min), and total emptying of solids (49.4 +/- 3.6 versus 50.5 +/- 5.0%) were not different from controls. Obese subjects had a trend to slowed liquid emptying (half-time 82.7 +/- 4.8 versus 69.9 +/- 6.9 min; emptying rate 0.59 +/- 0.03 versus 0.65 +/- 0.03%/min; total emptying 59.8 +/- 2.9 versus 66.0 +/- 3.3%), but this was not statistically significant. There was no correlation between weight or body surface area and rate of solid or liquid gastric emptying.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma lipoproteins and the synthesis and turnover of plasma triglyceride in normal and genetically obese mice

PubMed Central

Salmon, D. Michael W.; Hems, Douglas A.

1973-01-01

1. Lipoproteins in the plasma of mice were characterized by agarose-gel chromatography and polyacrylamide-gel electrophoresis: genetically obese (ob/ob) mice exhibited hyperlipoproteinaemia (compared with lean mice), largely owing to an increase in the concentration of cholesterol in high-density lipoprotein. Plasma concentrations of triglyceride and phospholipid were not markedly increased in genetically obese mice. 2. The formation of glycerolipids in liver and plasma was investigated with 14C-labelled precursors. The synthesis of hepatic triglyceride and phospholipid from glucose or palmitate was enhanced in ob/ob mice, compared with lean mice. The rate of entry of triglyceride into plasma, calculated from the time-course of incorporation of 14C from [14C]palmitate into plasma triglyceride, was increased in ob/ob mice (0.5μmol of fatty acid/min, compared with 0.2 in lean mice). 3. The removal from plasma of murine lipoprotein triglyceride-[14C]fatty acid was increased in ob/ob mice (half-time 2.2min, compared with 7.2min in lean mice). Similar results were obtained with an injected lipid emulsion (Intralipid). 4. From these measurements, estimates of the rates of turnover of plasma triglyceride in mice (fed on a mixed diet, female, 3 months old) are about 1.0μmol of fatty acid/min in ob/ob mice, and 0.25 in lean mice. 5. The major precursor of hepatic and plasma triglyceride in lean and ob/ob mice was calculated to be plasma free fatty acid. 6. These results are discussed, in connexion with the role of the liver in triglyceride metabolism in mice, especially in relation to genetic obesity. PMID:4360712

A Hydraulic Model Is Compatible with Rapid Changes in Leaf Elongation under Fluctuating Evaporative Demand and Soil Water Status1[C][W][OPEN

PubMed Central

Caldeira, Cecilio F.; Bosio, Mickael; Parent, Boris; Jeanguenin, Linda; Chaumont, François; Tardieu, François

2014-01-01

Plants are constantly facing rapid changes in evaporative demand and soil water content, which affect their water status and growth. In apparent contradiction to a hydraulic hypothesis, leaf elongation rate (LER) declined in the morning and recovered upon soil rehydration considerably quicker than transpiration rate and leaf water potential (typical half-times of 30 min versus 1–2 h). The morning decline of LER began at very low light and transpiration and closely followed the stomatal opening of leaves receiving direct light, which represent a small fraction of leaf area. A simulation model in maize (Zea mays) suggests that these findings are still compatible with a hydraulic hypothesis. The small water flux linked to stomatal aperture would be sufficient to decrease water potentials of the xylem and growing tissues, thereby causing a rapid decline of simulated LER, while the simulated water potential of mature tissues declines more slowly due to a high hydraulic capacitance. The model also captured growth patterns in the evening or upon soil rehydration. Changes in plant hydraulic conductance partly counteracted those of transpiration. Root hydraulic conductivity increased continuously in the morning, consistent with the transcript abundance of Zea maize Plasma Membrane Intrinsic Protein aquaporins. Transgenic lines underproducing abscisic acid, with lower hydraulic conductivity and higher stomatal conductance, had a LER declining more rapidly than wild-type plants. Whole-genome transcriptome and phosphoproteome analyses suggested that the hydraulic processes proposed here might be associated with other rapidly occurring mechanisms. Overall, the mechanisms and model presented here may be an essential component of drought tolerance in naturally fluctuating evaporative demand and soil moisture. PMID:24420931

Inhibitors of Serine/Threonine Protein Phosphatases: Biochemical and Structural Studies Provide Insight for Further Development.

PubMed

Swingle, Mark R; Honkanen, Richard Eric

2018-05-07

The reversible phosphorylation of proteins regulates many key functions in eukaryotic cells. Phosphorylation is catalyzed by protein kinases, with the majority of phosphorylation occurring on side chains of serine and threonine residues. The phosphomonoesters generated by protein kinases are hydrolyzed by protein phosphatases. In the absence of a phosphatase the half-time for the hydrolysis of alkyl phosphate dianions at 25º C is over 1 trillion years; knon ~2 x 10-20 sec-1. Therefore, ser/thr phosphatases are critical for processes controlled by reversible phosphorylation. This review is based on a search of the literature in available databases. We compare the catalytic mechanism of PPP-family phosphatases (PPPases) and the interactions of inhibitors that target these enzymes. PPPases are metal-dependent hydrolases that enhance the rate of hydrolysis ([kcat/kM]/knon ) by a factor of ~1021, placing them among the most powerful known catalysts on earth. Biochemical and structural studies indicate the remarkable catalytic proficiencies of PPPases are achieved by 10 conserved amino acids, DXH(X)~26DXXDR(X)~20-26NH(X)~50H(X)~25-45R(X)~30-40H. Six act as metal-coordinating residues. Four position and orient the substrate phosphate. Together, two metal ions and the 10 catalytic residues position the phosphoryl group and an activated bridging water/hydroxide nucleophile for inline attack upon the substrate phosphorous atom. The PPPases are conserved among species, and many structurally diverse natural toxins co-evolved to target these enzymes. Although the catalytic site is conserved, opportunities for the development of selective inhibitors of this important group of metalloenzymes exist. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Bacterial infection and acute lung injury in hamsters.

PubMed

Seidenfeld, J J; Mullins, R C; Fowler, S R; Johanson, W G

1986-07-01

Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome. We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle. Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally. Lung and systemic antibacterial defenses were studied at death 24 h later. Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and resulted in a 12% (3 of 26) mortality. PAO1 alone caused focal pneumonias and no deaths. Animals receiving both agents (PAO1/PQ) had extensive diffuse alveolar damage characterized by alveolar hemorrhage, edema, influx of neutrophils, and vasculitis; 50% (16 of 32) died within 96 h of PQ injection. Mean lung counts of PAO1 at death were 7.6 X 10(4) colony forming units/g in PAO1 and 2.8 X 10(7) in PAO1/PQ animals (p less than 0.05). PAO1 colony counts in liver were increased nearly 100-fold in PAO1/PQ animals (p less than 0.05). Half-time of clearance of P. aeruginosa from the blood was prolonged in PAO1 and in PAO1/PQ animals (p less than 0.05) but not in PQ animals. Phagocytosis of Staphylococcus aureus by leukocytes lavaged from the lung was not impaired in any group compared with that in control animals, but intracellular killing was impaired in PAO1 and PAO1/PQ but not in PQ animals. Paraquat injury impairs lung antibacterial defenses by uncertain mechanisms. Superinfection of PQ-injured lungs by PAO1 appears responsible for defects in intrapulmonary and systemic antibacterial defenses.

Clarithromycin accumulation by phagocytes and its effect on killing of Aggregatibacter actinomycetemcomitans.

PubMed

Iskandar, Irma; Walters, John D

2011-03-01

Clarithromycin inhibits several periodontal pathogens and is concentrated inside gingival fibroblasts and epithelial cells by an active transporter. We hypothesized that polymorphonuclear leukocytes (PMNs) and less mature myeloid cells possess a similar transporter for clarithromycin. It is feasible that clarithromycin accumulation inside PMNs could enhance their ability to kill Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans). To test the first hypothesis, purified PMNs and cultured HL-60 cells were incubated with [(3)H]-clarithromycin. Clarithromycin transport was assayed by measuring changes in cell-associated radioactivity over time. The second hypothesis was examined with PMNs loaded by incubation with clarithromycin (5 μg/ml). Opsonized bacteria were incubated at 37°C with control and clarithromycin-loaded PMNs. Mature human PMNs, HL-60 cells differentiated into granulocytes, and undifferentiated HL-60 cells all took up clarithromycin in a saturable manner. The kinetics of uptake by all yielded linear Lineweaver-Burk plots. HL-60 granulocytes transported clarithromycin with a K(m) of ≈250 μg/ml and a V(max) of 473 ng/min/10(6) cells, which were not significantly different from the values obtained with PMNs. At steady state, clarithromycin levels inside HL-60 granulocytes and PMNs were 28- to 71-fold higher than extracellular levels. Clarithromycin-loaded PMNs killed significantly more A. actinomycetemcomitans and achieved shorter half-times for killing than control PMNs when assayed at a bacteria-to-PMN ratio of 100:1 (P <0.04). At a ratio of 30:1, these differences were not consistently significant. PMNs and less mature myeloid cells possess a transporter that takes up and concentrates clarithromycin. This system could help PMNs cope with an overwhelming infection by A. actinomycetemcomitans.

A comparison of isomaltulose versus maltodextrin ingestion during soccer-specific exercise.

PubMed

Stevenson, Emma J; Watson, Anthony; Theis, Stephan; Holz, Anja; Harper, Liam D; Russell, Mark

2017-11-01

The performance and physiological effects of isomaltulose and maltodextrin consumed intermittently during prolonged soccer-specific exercise were investigated. University soccer players (n = 22) performed 120 min of intermittent exercise while consuming 8% carbohydrate-electrolyte drinks (equivalent to ~ 20 g h -1 ) containing maltodextrin (Glycaemic Index: 90-100), isomaltulose (Glycaemic Index: 32) or a carbohydrate-energy-free placebo in a manner replicating the practices of soccer players (i.e., during warm-up and half-time). Physical (sprinting, jumping) and technical (shooting, dribbling) performance was assessed. Blood glucose and plasma insulin (both P < 0.001) concentrations varied by trial with isomaltulose maintaining > 13% higher blood glucose concentrations between 75 and 90 min versus maltodextrin (P < 0.05). A decline in glycaemia at 60 min in maltodextrin was attenuated with isomaltulose (-19 versus -4%; P = 0.015). Carbohydrates attenuated elevations in plasma epinephrine concentrations (P < 0.05), but isomaltulose proved most effective at 90 and 120 min. Carbohydrates did not attenuate IL-6 increases or reductions in physical or technical performances (all P > 0.05). Ratings of abdominal discomfort were influenced by trial (P < 0.05) with lower values for both carbohydrates compared to PLA from 60 min onwards. Although carbohydrates (~ 20 g h -1 ) did not attenuate performance reductions throughout prolonged soccer-specific exercise, isomaltulose maintained higher blood glucose at 75-90 min, lessened the magnitude of the exercise-induced rebound glycaemic response and attenuated epinephrine increases whilst maintaining similar abdominal discomfort values relative to maltodextrin. When limited opportunities exist to consume carbohydrates on competition-day, low-glycaemic isomaltulose may offer an alternative nutritional strategy for exercising soccer players.

Gastric emptying, intestinal absorption of electrolytes and exercise performance in electrolyte-supplemented horses.

PubMed

Lindinger, Michael I; Ecker, Gayle L

2013-01-01

Horses lose considerably more electrolytes through sweating during prolonged exercise than can be readily replaced through feeds. The present study tested an oral electrolyte supplement (ES) designed to replace sweat electrolyte losses. We measured gastric emptying of 3 litres of ES (using gamma imaging of (99)Tc-sulfide colloid), the absorption of Na(+) and K(+) from the gastrointestinal tract using (24)Na(+) and (42)K(+), and the distribution of these ions in the body by measuring radioactivity within plasma and sweat during exercise. Three litres of ES emptied from the stomach as fast as water, with a half-time of 47 min, and appeared in plasma by 10 min after administration (n = 4 horses). Peak values of plasma (24)Na(+) and (42)K(+) radioactivity occurred at 20-40 min, and a more rapid disappearance of K(+) radioactivity from plasma was indicative of movement of K(+) into cells (n = 3 horses). In a randomized crossover experiment (n = 4 horses), 1 h after administration of placebo (water), 1 or 3 litres of ES containing (24)Na(+), horses exercised on a treadmill at 30% of peak oxygen uptake until voluntary fatigue. The (24)Na(+) appeared in sweat at 10 min of exercise, and when horses received 3 litres of ES the duration to voluntary fatigue was increased in all horses by 33 ± 10%. It is concluded that an oral ES designed to replace sweat ion losses was rapidly emptied from the gastrointestinal tract, rapidly absorbed in the upper intestinal tract and rapidly distributed within the body. The ES clearly served as a reservoir to replace sweat ion losses during exercise, and administration of ES prior to exercise resulted in increased duration of submaximal exercise.

LC3 fluorescent puncta in autophagosomes or in protein aggregates can be distinguished by FRAP analysis in living cells

PubMed Central

Wang, Liang; Chen, Min; Yang, Jie; Zhang, Zhihong

2013-01-01

LC3 is a marker protein that is involved in the formation of autophagosomes and autolysosomes, which are usually characterized and monitored by fluorescence microscopy using fluorescent protein-tagged LC3 probes (FP-LC3). FP-LC3 and even endogenous LC3 can also be incorporated into intracellular protein aggregates in an autophagy-independent manner. However, the dynamic process of LC3 associated with autophagosomes and autolysosomes or protein aggregates in living cells remains unclear. Here, we explored the dynamic properties of the two types of FP-LC3-containing puncta using fluorescence microscopy techniques, including fluorescence recovery after photobleaching (FRAP) and fluorescence resonance energy transfer (FRET). The FRAP data revealed that the fluorescent signals of FP-LC3 attached to phagophores or in mature autolysosomes showed either minimal or no recovery after photobleaching, indicating that the dissociation of LC3 from the autophagosome membranes may be very slow. In contrast, FP-LC3 in the protein aggregates exhibited nearly complete recovery (more than 80%) and rapid kinetics of association and dissociation (half-time < 1 sec), indicating a rapid exchange occurs between the aggregates and cytoplasmic pool, which is mainly due to the transient interaction of LC3 and SQSTM1/p62. Based on the distinct dynamic properties of FP-LC3 in the two types of punctate structures, we provide a convenient and useful FRAP approach to distinguish autophagosomes from LC3-involved protein aggregates in living cells. Using this approach, we find the FP-LC3 puncta that adjacently localized to the phagophore marker ATG16L1 were protein aggregate-associated LC3 puncta, which exhibited different kinetics compared with that of autophagic structures. PMID:23482084

Match and mismatch between opening area and resistance in mild and moderate rheumatic mitral stenosis.

PubMed

El-Dosouky, Ibtesam Ibrahim

2016-12-01

Mitral valve resistance (MVR) is a hemodynamic consequence of mitral stenosis (MS), but it has no clear threshold with a shortage of data to be reliable. We aimed to investigate match and mismatch between opening area and resistance especially in patients with moderate and mild MS. This study comprised 88 patients with moderate and mild rheumatic MS. Transthoracic echocardiographic study estimated the following: mitral valve area (MVA) by both planimetry (2D) and pressure half-time (PHT), mitral valve score (MVS), mean transmitral pressure gradient (MPG), diastolic filling time (DFT), left ventricular out flow tract diameter (LVOTd) and velocity-time integral (LVOTvti), and MVR = MPG/aortic flow ratio [(LVOTd) (LVOTvti)/DFT] in dynes·s/cm 5 . Patients were classified into two groups: group 1 (51 patients) with matched MVR and group 2 (37 patients) with mismatched higher MVR. In the matched group, moderate MS showed MVR <105 dynes·s/cm 5 and <76dynes·s/cm 5 with mild MS. Group 2 compared to group 1 had higher NYHA class (1.4±0.6 vs 1.2±0.4, P<.05) and higher MVS (8.1±1.8 vs 7±0.9, P<.05). MVR showed positive correlation with MVS (r=.5, P<.05), and logistic regression analysis showed that MVS is the only independent predictor of the MVR severity in the mismatched group (i.e., with higher MVR compared to the ROC analysis results) (B±SE=6.997±2.826, t=2.476, 95% CI 1.241±12.752 with an odds ratio=0.412, P<.05). On investigating match and mismatch between opening area and resistance, the only independent predictor of mismatch is the mitral valve score. © 2016, Wiley Periodicals, Inc.

Biodegradation of hydrocarbon mixtures in surface waters at environmentally relevant levels - Effect of inoculum origin on kinetics and sequence of degradation.

PubMed

Birch, Heidi; Hammershøj, Rikke; Comber, Mike; Mayer, Philipp

2017-10-01

Biodegradation is a dominant removal process for many organic pollutants, and biodegradation tests serve as tools for assessing their environmental fate within regulatory risk assessment. In simulation tests, the inoculum is not standardized, varying in microbial quantity and quality, thereby potentially impacting the observed biodegradation kinetics. In this study we investigated the effect of inoculum origin on the biodegradation kinetics of hydrocarbons for five inocula from surface waters varying in urbanization and thus expected pre-exposure to petroleum hydrocarbons. A new biodegradation method for testing mixtures of hydrophobic chemicals at trace concentrations was demonstrated: Aqueous solutions containing 9 hydrocarbons were generated by passive dosing and diluted with surface water resulting in test systems containing native microorganisms exposed to test substances at ng-μg/L levels. Automated Headspace Solid Phase Microextraction coupled to GC-MS was applied directly to these test systems to determine substrate depletion relative to abiotic controls. Lag phases were generally less than 8 days. First order rate constants were within one order of magnitude for each hydrocarbon in four of the five waters but lower in water from a rural lake. The sequence of degradation between the 9 hydrocarbons showed similar patterns in the five waters indicating the potential for using selected hydrocarbons for benchmarking between biodegradation tests. Degradation half-times were shorter than or within one order of magnitude of BioHCwin predictions for 8 of 9 hydrocarbons. These results showed that location choice is important for biodegradation kinetics and can provide a relevant input to aquatic exposure and fate models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.

PubMed

Vazquez Roque, Maria I; Camilleri, Michael; Stephens, Debra A; Jensen, Michael D; Burton, Duane D; Baxter, Kari L; Zinsmeister, Alan R

2006-12-01

Peptide YY (PYY) levels are reported to be decreased in obesity. The relation between gastric functions, satiation, and gut hormones in obesity is incompletely understood. The aim of this study was to compare gastric volumes, emptying, maximum tolerated volumes, postchallenge symptoms, and selected gut hormones in normal, overweight, or obese healthy volunteers. In 73 nonbulimic normal, overweight, or obese participants weighing less than 137 kg, we measured gastric emptying of solids and liquids by scintigraphy (gastric emptying half-time [GE t(1/2)]); gastric volumes by single-photon emission computed tomography; maximum tolerated volumes and symptoms by satiation test; and plasma leptin, ghrelin, insulin, glucagon-like peptide 1, and PYY levels. Groups were compared using 1-way analysis of covariance adjusted for sex. Univariate associations among measured responses were assessed using Spearman correlations. Multiple linear regression models, adjusting for weight and sex, assessed the independent ability of gastric functions and hormones to predict satiation volume. Obese and overweight subjects had significantly lower postprandial gastric volumes, higher fasting and postprandial insulin and leptin levels, and lower fasting ghrelin and lower postprandial reduction in ghrelin levels. PYY levels were not different in obese or overweight subjects compared with controls. The GE t(1/2) was correlated inversely with postprandial PYY; increased body weight was associated with faster GE t(1/2) of solids (r(s) = 0.33, P = .005) and liquids (r(s) = 0.24, P = .04). Postprandial changes in gastric volume and PYY were independent predictors of satiation (both P = .01). Overweight or obesity are associated with lower postprandial gastric volumes and normal PYY levels. Gastric emptying influences postprandial PYY levels. Postprandial PYY and gastric volume independently predict satiation volume in nonbulimic people across a wide body mass index range.

Fate of inhaled azodicarbonamide in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mewhinney, J.A.; Ayres, P.H.; Bechtold, W.E.

Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation tomore » ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of (/sup 14/C)ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only /sup 14/C-labeled compound present in excreta. (/sup 14/C)ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for (/sup 14/C)ADA equivalents were not observed. The rate of buildup of (/sup 14/C)ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of (/sup 14/C)ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine.« less

Pattern of uptake of americium-241 by the rat skeleton and its subsequent redistribution and retention: implications for human dosimetry and toxicology.

PubMed

Priest, N D; Howells, G; Green, D; Haines, J W

1983-01-01

The distribution and retention of intravenously injected 241Am in the skeleton of the female rat has been investigated using autoradiographic and radiochemical techniques. The studies were designed to assess the dosimetric and toxicologic implications of an 241Am intake by man. They showed that in the rat approximately one third of the intravenously injected 241Am was deposited in the skeleton where it appeared to be retained with a long biological half-time. The studies also showed: 1 241Am is initially deposited onto all types of bone surface including endosteal surfaces, periosteal surfaces and those of the vascular canals within cortical bone, but seems to be preferentially deposited onto those that are resorbing, 2 Bone accretion results in the burial of surface deposits of 241Am, 3 Bone resorption causes the removal of 241Am from surfaces, 4 Resorbed 241Am is retained by phagocytic cells (probably macrophages) in the bone marrow, 5 The transfer of 241Am from the phagocytic cells in the marrow to adjacent bone surfaces seems to occur, (local recycling). 6 The possibility that some of the 241Am removed from the bone surfaces enters the blood and is redeposited in bone, (systemic recycling) cannot be dismissed. These results show that 241Am deposition and redistribution in bone shares many characteristics with other 'bone surface-seeking radionuclides' typified by 239Pu. Consequently, it is suggested that a similar model to that used to calculate annual limits of intake for 239Pu in man would be suitable for the calculation of corresponding values for the 241Am isotopes.

Longitudinal study of veterinarians from entry to the veterinary course to 10 years after graduation: attitudes to work, career and profession.

PubMed

Heath, T J

2002-08-01

To describe the attitudes of veterinarians to their work, career and profession during the 10 years after graduation. Longitudinal study of students who started their course at The University of Queensland in 1985 and 1986, and who completed questionnaires in their first and fifth year as students, and after one, five and 10 years as veterinarians. Data from 129 (96%) questionnaires completed after 10 years as a veterinarian were coded numerically then analysed, together with data from previous questionnaires, with SAS System 7 for Windows 95. After 10 years, almost all respondents were either very glad they had done the veterinary course (57%) or generally glad, though with some misgivings (37%). Despite this, only 55% would definitely become a veterinarian if they 'had to do it over again'. The responses for about one-third were different from those given five years earlier. The views of many were related to the level of support and encouragement received in their first job after graduation. There were 42% who were working less than half-time as veterinarians, and their main reasons were, in order, raising children, long hours of work, attitudes of bosses and clients, and poor pay. A majority was concerned about the ethics and competence of some colleagues, and almost all believed that consideration of costs must influence the type of treatment animals receive. Most veterinarians were glad to have done the veterinary course, but for about one-quarter their career had not lived up to expectations and almost half would not do it again in another incarnation. Stress, hours of work, difficulties in balancing personal life with career and low income were important concerns for many. Low income may contribute to the low number of males entering the veterinary profession.

Region of birth, sex, and agricultural work of immigrant Latino farm workers: the MICASA study.

PubMed

McCurdy, S A; Stoecklin-Marois, M T; Tancredi, D J; Bennett, D H; Schenker, M B

2014-04-01

Agricultural work is hazardous, and immigrant workers perform the majority of production tasks, yet there are few data describing agricultural work and use of protective measures by demographic characteristics. We examined cross-sectionally the influence of region of birth (Mexico vs. Central America) and sex on agricultural work and use of protective measures in the MICASA cohort of immigrant Latino farm workers in Mendota, California. Of 445 participants, 293 (65.8%) were born in Mexico (163 men, 130 women) and 152 (34.2%) were born in Central America (80 men, 72 women). Men worked on average 74.4 more days than women (95% CI 62.0, 86.9) and were more likely to perform tasks requiring high levels of training or strength, such as machine operation, pruning, picking, planting, and irrigation; more likely to work in dusty conditions; and more likely to work directly with pesticides. Women predominated in packing. Respondents from Mexico were more likely to work with tomatoes and less likely to work with melon and lettuce. Central America-born respondents were less likely to engage in planting, irrigation, and pesticide use. Use of task-appropriate personal protective measures on at least a half-time basis was rare, with the exception of persons working with pesticides (a group limited to men) and for facial scarves among Central American women. Further work should focus on identifying barriers to use of preventive measures and programs to further their use. Educational models accounting for cultural factors and driving social norm change, employer engagement, and use of community health workers (promotores) may be helpful in promoting use of preventive measures.

Expression of a dominant allele of human ARF1 inhibits membrane traffic in vivo

PubMed Central

1994-01-01

ADP-ribosylation factor (ARF) proteins and inhibitory peptides derived from ARFs have demonstrated activities in a number of in vitro assays that measure ER-to-Golgi and intra-Golgi transport and endosome fusion. To better understand the roles of ARF proteins in vivo, stable cell lines were obtained from normal rat kidney (NRK) cells transfected with either wild-type or a dominant activating allele ([Q71L]) of the human ARF1 gene under the control of the interferon-inducible mouse Mx1 promoter. Upon addition of interferon, expression of ARF1 proteins increased with a half-time of 7-8 h, as determined by immunoblot analysis. Induction of mutant ARF1, but not wild-type ARF1, led to an inhibition of protein secretion with kinetics similar to that observed for induction of protein expression. Examination of the Golgi apparatus and the ER by indirect immunofluorescence or transmission electron microscopy revealed that expression of low levels of mutant ARF1 protein correlated with a dramatic increase in vesiculation of the Golgi apparatus and expansion of the ER lumen, while expression of substantially higher levels of wild-type ARF1 had no discernible effect. Endocytosis was also inhibited by expression of mutant ARF1, but not by the wild-type protein. Finally, the expression of [Q71L]ARF1, but not wild-type ARF1, antagonized the actions of brefeldin A, as determined by the delayed loss of ARF and beta-COP from Golgi membranes and disruption of the Golgi apparatus. General models for the actions of ARF1 in membrane traffic events are discussed. PMID:8294513

Shear stress and flow dynamics of the femoral vein among obese patients who qualify for bariatric surgery.

PubMed

Wiewiora, Maciej; Piecuch, Jerzy; Glűck, Marek; Slowinska-Lozynska, Ludmila; Sosada, Krystyn

2013-01-01

The aim of this study was to evaluate the effects of obesity on wall shear stress and its relationship to erythrocyte aggregation. We studied 35 morbidly obese patients who were qualified for bariatric surgery. The control group consisted of 20 non-obese people. Blood rheological measurements were performed using the Laser-assisted Optical Rotational Cell Analyzer (Mechatronics, the Netherlands) and a cone-plate viscometer (Brookfield DV-II). The venous flow dynamics were assessed using a duplex ultrasound. The shear rate was estimated from the measured blood flow velocity and the diameter of the femoral vein. Venous wall shear stress was calculated from the whole blood viscosity and the shear rate. The shear rate (P < 0.005) and the venous wall shear stress (P < 0.05) were significantly lower in obese patients compared with the controls. The aggregation index (P < 0.001), syllectogram amplitude - AMP (P < 0.05) and Tslow (P < 0.001) were significantly higher in the obese patients; the aggregation half-time (P < 0.001) and Tfast (P < 0.001) were decreased compared with the control group. Multivariate regression analyses found waist circumference (β -0.31, P < 0.05), thigh circumference (β 0.33, P < 0.05) and Tslow (β -0.47, P < 0.005) to be variables that independently influenced the shear rate. Nevertheless, the AMP (β 0.34, P < 0.05) and Tslow (β -0.47, P < 0.01) were independent predictors that influenced the wall shear stress. This study indicates that there is a relationship between wall shear stress in the femoral vein and the rheological impairment of the RBC among obese patients, but further studies are necessary to confirm this suggestion.

Urinary and proximal tubule acidification during reduction of renal blood flow in the rat.

PubMed Central

Jaramillo-Juárez, F; Aires, M M; Malnic, G

1990-01-01

1. The effects of reduction in renal blood flow (RBF) on urinary acidification and proximal tubule H+ ion secretion were studied after partial aortic clamping in rats. 2. Acute reduction of the renal perfusion pressure (from 109 +/- 3.88 to 77.4 +/- 1.05 mmHg) decreased both inulin and PAH (p-aminohippurate) clearances to about one-third of their control values. Absolute levels of urinary sodium excretion also decreased markedly, but fractional sodium excretion did not change significantly. 3. Urine pH and bicarbonate levels were not affected, but titratable acidity increased significantly from 0.12 +/- 0.011 to 0.25 +/- 0.042 muequiv min-1 ml-1 glomerular filtration rate (GFR). During aortic clamping, cortical PCO2 as determined by means of Severinghaus microelectrodes was reduced by a mean value of 7.0 +/- 1.5 mmHg. 4. Proximal tubule acidification kinetics were studied by stationary microperfusion techniques in which the time course of pH changes was monitored by pH microelectrodes. Steady-state pH fell from a mean control value of 6.77 +/- 0.03 to 6.65 +/- 0.02, and stationary bicarbonate concentrations from 4.70 +/- 0.27 to 2.84 +/- 0.18 mM. Acidification half-time decreased from 5.07 +/- 0.30 to 4.39 +/- 0.19 s, and net bicarbonate reabsorption increased from 1.63 +/- 0.14 to 1.99 +/- 0.12 nmol cm-2 s-1, these changes being statistically significant. 5. The experiments demonstrate that both overall acid excretion and proximal acid secretion are not compromised by a large decrease of RBF to about one-third of the control value; titratable acid excretion and proximal net bicarbonate reabsorption were even moderately increased under these conditions. PMID:2348400

Candida Drug Resistance Protein 1, a Major Multidrug ATP Binding Cassette Transporter of Candida albicans, Translocates Fluorescent Phospholipids in a Reconstituted System†

PubMed Central

Shukla, Sudhanshu; Rai, Versha; Saini, Preeti; Banerjee, Dibyendu; Menon, Anant K.; Prasad, Rajendra

2008-01-01

Candida albicans drug resistance protein 1 (Cdr1p), an ATP-dependent drug efflux pump, contributes to multidrug resistance in Candida-infected immunocompromised patients. Previous cell-based assays suggested that Cdr1p also acts as a phospholipid translocator. To investigate this, we reconstituted purified Cdr1p into sealed membrane vesicles. Comparison of the ATPase activities of sealed and permeabilized proteoliposomes indicated that Cdr1p was asymmetrically reconstituted such that ~70% of the molecules had their ATP binding sites accessible to the extravesicular space. Fluorescent glycerophospholipids were incorporated into the outer leaflet of the proteoliposomes, and their transport into the inner leaflet was tracked with a quenching assay using membrane-impermeant dithionite. We observed ATP-dependent transport of the fluorescent lipids into the inner leaflet of the vesicles. With ~6 molecules of Cdr1p per vesicle on average, the half-time to reach the maximal extent of transport was ~15 min. Transport was reduced in vesicles reconstituted with Cdr1p variants with impaired ATPase activity and could be competed out to different levels by a molar excess of drugs such as fluconazole and miconazole that are known to be effluxed by Cdr1p. Transport was not affected by ampicillin, a compound that is not effluxed by Cdr1p. Our results suggest a direct link between the ability of Cdr1p to translocate fluorescent phospholipids and efflux drugs. We note that only a few members of the ABC superfamily of Candida have a well-defined role as drug exporters; thus, lipid translocation mediated by Cdr1p could reflect its cellular function. PMID:17924650

High-temperature responses of North American cacti

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, S.D.; Didden-Zopfy, B.; Nobel, P.S.

1984-04-01

High-temperature tolerances of 14 species of North American cacti were investigated. A reduction in the proportion of chlorenchyma cells taking up a vital stain (neutral red) and reduced nocturnal acid accumulation were used as indicators of high-temperature damage. All species tolerated relatively high tissue temperatures, the mean maximum tolerance being 64/sup 0/C, with an absolute maximum of 69/sup 0/ for two species of ferocactus. Such tissue tolerances to high temperature may be unsurpassed in vascular plants. Morphological features can affect tissue temperatures. Specifically, thin-stemmed species such as the cylindropuntias attain lower maximum temperatures under identical microclimatic conditions than do moremore » massive species; they also tend to be less tolerant of high-temperature stress. Stem diameter changes of three species of columnar ceriod cacti along a Sonoran Desert latitudinal transect were previously attributed to adaptation to progressively colder temperatures northward. Such changes can also be interpreted as a morphological adaptation to high temperatures, particularly in the southern Sonoran Desert. Interspecific differences in high-temperature tolerance may account for distributional differences among other species. Acclimation of high-temperature tolerances in response to increasing day/night air temperatures was observed in all 14 species, especially at higher growh temperatures. From 40/sup 0/ day/30/sup 0/ night to 50/sup 0//40/sup 0/, the tolerable tissue temperatures increased an average of 6/sup 0/. Half-times for the acclimation shifts were 1-3d. Although cacti attain extremely high tissue temperatures in desert habitats, tolerance of high temperatures and pronounced acclimation potential allow them to occur in some of the hottest habitats in North America.« less

Perilymph pharmacokinetics of markers and dexamethasone applied and sampled at the lateral semi-circular canal.

PubMed

Salt, Alec N; Hartsock, Jared J; Gill, Ruth M; Piu, Fabrice; Plontke, Stefan K

2012-12-01

Perilymph pharmacokinetics was investigated by a novel approach, in which solutions containing drug or marker were injected from a pipette sealed into the perilymphatic space of the lateral semi-circular canal (LSCC). The cochlear aqueduct provides the outlet for fluid flow so this procedure allows almost the entire perilymph to be exchanged. After wait times of up to 4 h the injection pipette was removed and multiple, sequential samples of perilymph were collected from the LSCC. Fluid efflux at this site results from cerebrospinal fluid (CSF) entry into the basal turn of scala tympani (ST) so the samples allow drug levels from different locations in the ear to be defined. This method allows the rate of elimination of substances from the inner ear to be determined more reliably than with other delivery methods in which drug may only be applied to part of the ear. Results were compared for the markers trimethylphenylammonium (TMPA) and fluorescein and for the drug dexamethasone (Dex). For each substance, the concentration in fluid samples showed a progressive decrease as the delay time between injection and sampling was increased. This is consistent with the elimination of substance from the ear with time. The decline with time was slowest for fluorescein, was fastest for Dex, with TMPA at an intermediate rate. Simulations of the experiments showed that elimination occurred more rapidly from scala tympani (ST) than from scala vestibuli (SV). Calculated elimination half-times from ST averaged 54.1, 24.5 and 22.5 min for fluorescein, TMPA and Dex respectively and from SV 1730, 229 and 111 min respectively. The elimination of Dex from ST occurred considerably faster than previously appreciated. These pharmacokinetic parameters provide an important foundation for understanding of drug treatments of the inner ear.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaffer, Richard, E-mail: rickyshaffer@yahoo.co.u; Department of Clinical Oncology, Imperial College London National Health Service Trust, London; Pickles, Tom

Purpose: Prior studies have derived low values of alpha-beta ratio (a/ss) for prostate cancer of approximately 1-2 Gy. These studies used poorly matched groups, differing definitions of biochemical failure, and insufficient follow-up. Methods and Materials: National Comprehensive Cancer Network low- or low-intermediate risk prostate cancer patients, treated with external beam radiotherapy or permanent prostate brachytherapy, were matched for prostate-specific antigen, Gleason score, T-stage, percentage of positive cores, androgen deprivation therapy, and era, yielding 118 patient pairs. The Phoenix definition of biochemical failure was used. The best-fitting value for a/ss was found for up to 90-month follow-up using maximum likelihood analysis,more » and the 95% confidence interval using the profile likelihood method. Linear quadratic formalism was applied with the radiobiological parameters of relative biological effectiveness = 1.0, potential doubling time = 45 days, and repair half-time = 1 hour. Bootstrap analysis was performed to estimate uncertainties in outcomes, and hence in a/ss. Sensitivity analysis was performed by varying the values of the radiobiological parameters to extreme values. Results: The value of a/ss best fitting the outcomes data was >30 Gy, with lower 95% confidence limit of 5.2 Gy. This was confirmed on bootstrap analysis. Varying parameters to extreme values still yielded best-fit a/ss of >30 Gy, although the lower 95% confidence interval limit was reduced to 0.6 Gy. Conclusions: Using carefully matched groups, long follow-up, the Phoenix definition of biochemical failure, and well-established statistical methods, the best estimate of a/ss for low and low-tier intermediate-risk prostate cancer is likely to be higher than that of normal tissues, although a low value cannot be excluded.« less

Sugar uptake by intestinal basolateral membrane vesicles.

PubMed

Wright, E M; van Os, C H; Mircheff, A K

1980-03-27

A high yield of membrane vesicles was prepared from the basolateral surface of rat intestinal cells using an N2 cavitation bomb and density gradient centrifugation. The membranes were enriched 10-fold and were free of significatn contamination by brush border membranes and mitochondria. The rate of D-E114C]glucose and L-E13H]glucose uptake into the vesicle was measured using a rapid filtration technique. D-Glucose equilibrated within the vesicles with a half-time 1/25th that for L-glucose. The stereospecific uptake exhibited saturation kinetics with a Km of approx. 44 mM and a V of approx. 110 nmol . mg-1 min-1 at 10 degrees C. The activation energy for the process was 14 kcal . mol-1 below 15 degrees C and it approached 3 kcal . mol-1 above 22 degrees C. Carrier-mediated uptake was eliminated in the presence of 1 mM HgCl2 and 0.5 mM phloretin. The rate of transport was unaffected by the absence or presence of sodium concentration gradients. Competition studies demonstrated that all sugars with the D-glucose pyranose ring chair conformation shared the transport system, and that, with the possible exception of the -OH group at carbon No. 1, there were no specific requirements for an equatorial -OH group at any position in the pyranose ring. In the case of alpha-methyl-D-glucoside its inability to share the D-glucose transport system may be due to steric hindrance posed by the -OCH3 group rather than by a specific requirement for a free hydroxyl group at the position in the ring. It is concluded that sugars are transported across the basolateral membrane of the intestinal epithelium by a facilitated diffusion system reminiscent of that in human red blood cells.

Wax and cutin mutants of Arabidopsis: Quantitative characterization of the cuticular transport barrier in relation to chemical composition.

PubMed

Sadler, Christina; Schroll, Bettina; Zeisler, Viktoria; Waßmann, Friedrich; Franke, Rochus; Schreiber, Lukas

2016-09-01

Using (14)C-labeled epoxiconazole as a tracer, cuticular permeability of Arabidopsis thaliana leaves was quantitatively measured in order to compare different wax and cutin mutants (wax2, cut1, cer5, att1, bdg, shn3 and shn1) to the corresponding wild types (Col-0 and Ws). Mutants were characterized by decreases or increases in wax and/or cutin amounts. Permeances [ms(-1)] of Arabidopsis cuticles either increased in the mutants compared to wild type or were not affected. Thus, genetic changes in wax and cutin biosynthesis in some of the investigated Arabidopsis mutants obviously impaired the coordinated cutin and wax deposition at the outer leaf epidermal cell wall. As a consequence, barrier properties of cuticles were significantly decreased. However, increasing cutin and wax amounts by genetic modifications, did not automatically lead to improved cuticular barrier properties. As an alternative approach to the radioactive transport assay, changes in chlorophyll fluorescence were monitored after foliar application of metribuzine, an herbicide inhibiting electron transport in chloroplasts. Since both, half-times of photosynthesis inhibition as well as times of complete inhibition, in fact correlated with (14)C-epoxiconazole permeances, different rates of decline of photosynthetic yield between mutants and wild type must be a function of foliar uptake of the herbicide across the cuticle. Thus, monitoring changes in chlorophyll fluorescence, instead of conducting radioactive transport assays, represents an easy-to-handle and fast alternative evaluating cuticular barrier properties of different genotypes. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. Copyright © 2016 Elsevier B.V. All rights reserved.

Usefulness of Mitral Valve Prosthetic or Bioprosthetic Time Velocity Index Ratio to Detect Prosthetic or Bioprosthetic Mitral Valve Dysfunction.

PubMed

Luis, Sushil Allen; Blauwet, Lori A; Samardhi, Himabindu; West, Cathy; Mehta, Ramila A; Luis, Chris R; Scalia, Gregory M; Miller, Fletcher A; Burstow, Darryl J

2017-10-15

This study aimed to investigate the utility of transthoracic echocardiographic (TTE) Doppler-derived parameters in detection of mitral prosthetic dysfunction and to define optimal cut-off values for identification of such dysfunction by valve type. In total, 971 TTE studies (647 mechanical prostheses; 324 bioprostheses) were compared with transesophageal echocardiography for evaluation of mitral prosthesis function. Among all prostheses, mitral valve prosthesis (MVP) ratio (ratio of time velocity integral of MVP to that of left ventricular outflow tract; odds ratio [OR] 10.34, 95% confidence interval [95% CI] 6.43 to 16.61, p<0.001), E velocity (OR 3.23, 95% CI 1.61 to 6.47, p<0.001), and mean gradient (OR 1.13, 95% CI 1.02 to 1.25, p=0.02) provided good discrimination of clinically normal and clinically abnormal prostheses. Optimal cut-off values by receiver operating characteristic analysis for differentiating clinically normal and abnormal prostheses varied by prosthesis type. Combining MVP ratio and E velocity improved specificity (92%) and positive predictive value (65%) compared with either parameter alone, with minimal decline in negative predictive value (92%). Pressure halftime (OR 0.99, 95% CI 0.98 to 1.00, p=0.04) did not differentiate between clinically normal and clinically abnormal prostheses but was useful in discriminating obstructed from normal and regurgitant prostheses. In conclusion, cut-off values for TTE-derived Doppler parameters of MVP function were specific to prosthesis type and carried high sensitivity and specificity for identifying prosthetic valve dysfunction. MVP ratio was the best predictor of prosthetic dysfunction and, combined with E velocity, provided a useful parameter for determining likelihood of dysfunction and need for further assessment. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Advancing Novel Anesthetics: Pharmacodynamic and Pharmacokinetic Studies of Cyclopropyl-Methoxycarbonyl Metomidate in Dogs

PubMed Central

Campagna, Jason A.; Pojasek, Kevin; Grayzel, David; Randle, John; Raines, Douglas E.

2014-01-01

Background Cyclopropyl-methoxycarbonyl metomidate (CPMM, also known as ABP-700) is a second-generation “soft” (i.e., metabolically-labile) etomidate analogue. The purpose of these studies was to characterize CPMM's pharmacology in beagle dogs in preparation for potential first in human phase 1 clinical trials. Methods CPMM's and etomidate's hypnotic activity and duration of action were assessed using loss of righting reflex and anesthesia score assays in three or four dogs. Their pharmacokinetics were defined after single bolus administration and single bolus followed by 2-h infusion. Adrenocortical recovery times after single bolus followed by 2-h infusion of CPMM, propofol, etomidate, and vehicle were measured using an adrenocorticotropic hormone stimulation test. Results Compared to etomidate, CPMM was half as potent as a hypnotic (ED50 ~ 0.8 mg/kg), more rapidly metabolized, and had a shorter duration of sedative-hypnotic action. Recovery times after CPMM administration were also independent of infusion duration. After hypnotic infusion, adrenocorticotropic hormone-stimulated plasma cortisol concentrations were 4- to 27-fold higher in dogs that received CPMM versus etomidate. Adrenocortical recovery was faster in dogs after CPMM infusion versus etomidate infusion (half-time: 215 min vs. 1623 min, respectively). Adrenocortical responsiveness assessed 90 min after CPMM infusion was not significantly different from that after propofol infusion. Conclusion Our studies in dogs confirm that CPMM has hypnotic and adrenocortical recovery profiles that are superior than those of etomidate, supporting the continued development of CPMM as a clinical sedative-hypnotic to be used as a single bolus and by continuous infusion to induce and maintain general anesthesia or procedural sedation. PMID:25170571

Streptococcal serum opacity factor promotes cholesterol ester metabolism and bile acid secretion in vitro and in vivo.

PubMed

Gillard, Baiba K; Rodriguez, Perla J; Fields, David W; Raya, Joe L; Lagor, William R; Rosales, Corina; Courtney, Harry S; Gotto, Antonio M; Pownall, Henry J

2016-03-01

Plasma high density lipoprotein-cholesterol (HDL-C) concentrations negatively correlate with atherosclerotic cardiovascular disease. HDL is thought to have several atheroprotective functions, which are likely distinct from the epidemiological inverse relationship between HDL-C levels and risk. Specifically, strategies that reduce HDL-C while promoting reverse cholesterol transport (RCT) may have therapeutic value. The major product of the serum opacity factor (SOF) reaction versus HDL is a cholesteryl ester (CE)-rich microemulsion (CERM), which contains apo E and the CE of ~400,000 HDL particles. Huh7 hepatocytes take up CE faster when delivered as CERM than as HDL, in part via the LDL-receptor (LDLR). Here we compared the final RCT step, hepatic uptake and subsequent intracellular processing to cholesterol and bile salts for radiolabeled HDL-, CERM- and LDL-CE by Huh7 cells and in vivo in C57BL/6J mice. In Huh7 cells, uptake from LDL was greater than from CERM (2-4X) and HDL (5-10X). Halftimes for [(14)C]CE hydrolysis were 3.0±0.2, 4.4±0.6 and 5.4±0.7h respectively for HDL, CERM and LDL-CE. The fraction of sterols secreted as bile acids was ~50% by 8h for all three particles. HDL, CERM and LDL-CE metabolism in mice showed efficient plasma clearance of CERM-CE, liver uptake and metabolism, and secretion as bile acids into the gall bladder. This work supports the therapeutic potential of the SOF reaction, which diverts HDL-CE to the LDLR, thereby increasing hepatic CE uptake, and sterol disposal as bile acids. Copyright © 2015 Elsevier B.V. All rights reserved.

Pulmonary function, bronchial reactivity, and epithelial permeability are response phenotypes to ozone and develop differentially in healthy humans.

PubMed

Que, Loretta G; Stiles, Jane V; Sundy, John S; Foster, W Michael

2011-09-01

Effect of laboratory exposure to O₃ (220 ppb) and filtered air (FA) on respiratory physiology were evaluated at two time points (acute and 1 day postexposure) in healthy cohort (n = 138, 18-35 yr, 40% women) comprised mainly of Caucasian (60%) and African American (33.3%) subjects. Randomized exposures had a crossover design and durations of 2.25 h that included rest and treadmill walking. Airway responsiveness (AHR) to methacholine (Mch) and permeability of respiratory epithelium (EI) to hydrophilic radiomarker ((99m)Tc-DTPA, MW = 492), were measured at 1-day postexposure. O₃ significantly affected FEV₁ and FVC indices acutely with mean decrements from pre-exposure values on the order of 7.7 to 8.8% and 1.8 to 2.3% at 1-day post. Acute FEV₁ and FVC decreases were most robust in African American male subjects. At 1-day post, O₃ induced significant changes in AHR (slope of Mch dose response curve) and EI (Tc(99m)-DTPA clearance half-time). Based on conventional thresholds of response and dichotomous classification of subjects as responders and nonresponders, sensitivity to O₃ was shown to be nonuniform. Acute decrements ≥ 15% in FEV₁, a doubling of Mch slope, or ≥ 15% increase in EI developed in 20.3%, 23.1%, and 25.9%, respectively, of subjects evaluated. Results demonstrate a diffuse sensitivity to O₃ and physiological responses, either acutely (decreases in FEV₁) or 1 day post (development of AHR or change in EI) occur differentially in healthy young adults. Random overlap among subjects classified as responsive for respective FEV₁, AHR, and EI endpoints suggests these are separate and independent phenotypes of O₃ exposure.

Pulmonary function, bronchial reactivity, and epithelial permeability are response phenotypes to ozone and develop differentially in healthy humans

PubMed Central

Que, Loretta G.; Stiles, Jane V.; Sundy, John S.

2011-01-01

Effect of laboratory exposure to O3 (220 ppb) and filtered air (FA) on respiratory physiology were evaluated at two time points (acute and 1 day postexposure) in healthy cohort (n = 138, 18–35 yr, 40% women) comprised mainly of Caucasian (60%) and African American (33.3%) subjects. Randomized exposures had a crossover design and durations of 2.25 h that included rest and treadmill walking. Airway responsiveness (AHR) to methacholine (Mch) and permeability of respiratory epithelium (EI) to hydrophilic radiomarker (99mTc-DTPA, MW = 492), were measured at 1-day postexposure. O3 significantly affected FEV1 and FVC indices acutely with mean decrements from pre-exposure values on the order of 7.7 to 8.8% and 1.8 to 2.3% at 1-day post. Acute FEV1 and FVC decreases were most robust in African American male subjects. At 1-day post, O3 induced significant changes in AHR (slope of Mch dose response curve) and EI (Tc99m-DTPA clearance half-time). Based on conventional thresholds of response and dichotomous classification of subjects as responders and nonresponders, sensitivity to O3 was shown to be nonuniform. Acute decrements ≥15% in FEV1, a doubling of Mch slope, or ≥15% increase in EI developed in 20.3%, 23.1%, and 25.9%, respectively, of subjects evaluated. Results demonstrate a diffuse sensitivity to O3 and physiological responses, either acutely (decreases in FEV1) or 1 day post (development of AHR or change in EI) occur differentially in healthy young adults. Random overlap among subjects classified as responsive for respective FEV1, AHR, and EI endpoints suggests these are separate and independent phenotypes of O3 exposure. PMID:21700892

Investigation on the durability of man-made vitreous fibers in rat lungs.

PubMed Central

Bellmann, B; Muhle, H; Kamstrup, O; Draeger, U F

1994-01-01

Two types of sized stonewool with median lengths of 6.7 and 10.1 microns and median diameters of 0.63 and 0.85 microns, and crocidolite with fibers of median length of 4.8 microns and median diameter of 0.18 microns were instilled intratracheally into female Wistar rats. A single dose of 2 mg in 0.3 ml saline was used for the stonewool samples and 0.1 mg in 0.3 ml saline for crocidolite. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM). Five animals per group were sacrificed after 2 days, 1, 3, 6, and 12 months. After low-temperature ashing of the lungs about 200 fibers per animal were analyzed by SEM for length and diameter. The number and mass of fibers in the total lung were calculated. For the stonewool samples the decrease in the number of fibers in the lung ash followed approximately first order kinetics resulting in half-times of 90 and 120 days. The analysis of fiber number and diameter of different length fractions was used to estimate the contribution of three processes of fiber elimination: transport by macrophages for short fibers, breakage of fibers, and dissolution of fibers. (The process of transport by macrophages was found fastest for fibers with length < 2.5 microns). For the elimination of critical fibers with length > 5 microns, the breakage and dissolution were the most important processes. The breakage of fibers was predominant for one of the stonewool samples. The preferential type of the mechanism of fiber elimination is dependent on chemical composition and size distribution. PMID:7882927

Rapid Diffusion of Green Fluorescent Protein in the Mitochondrial Matrix

PubMed Central

Partikian, Arthur; Ölveczky, Bence; Swaminathan, R.; Li, Yuxin; Verkman, A.S.

1998-01-01

Abstract. It is thought that the high protein density in the mitochondrial matrix results in severely restricted solute diffusion and metabolite channeling from one enzyme to another without free aqueous-phase diffusion. To test this hypothesis, we measured the diffusion of green fluorescent protein (GFP) expressed in the mitochondrial matrix of fibroblast, liver, skeletal muscle, and epithelial cell lines. Spot photobleaching of GFP with a 100× objective (0.8-μm spot diam) gave half-times for fluorescence recovery of 15–19 ms with >90% of the GFP mobile. As predicted for aqueous-phase diffusion in a confined compartment, fluorescence recovery was slowed or abolished by increased laser spot size or bleach time, and by paraformaldehyde fixation. Quantitative analysis of bleach data using a mathematical model of matrix diffusion gave GFP diffusion coefficients of 2–3 × 10−7 cm2/s, only three to fourfold less than that for GFP diffusion in water. In contrast, little recovery was found for bleaching of GFP in fusion with subunits of the fatty acid β-oxidation multienzyme complex that are normally present in the matrix. Measurement of the rotation of unconjugated GFP by time-resolved anisotropy gave a rotational correlation time of 23.3 ± 1 ns, similar to that of 20 ns for GFP rotation in water. A rapid rotational correlation time of 325 ps was also found for a small fluorescent probe (BCECF, ∼0.5 kD) in the matrix of isolated liver mitochondria. The rapid and unrestricted diffusion of solutes in the mitochondrial matrix suggests that metabolite channeling may not be required to overcome diffusive barriers. We propose that the clustering of matrix enzymes in membrane-associated complexes might serve to establish a relatively uncrowded aqueous space in which solutes can freely diffuse. PMID:9472034

Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man.

PubMed

Adrian, T E; Sagor, G R; Savage, A P; Bacarese-Hamilton, A J; Hall, G M; Bloom, S R

1986-10-01

Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.

In Vivo Measurement in Pigs of Wash-In Kinetics of Xenon at its Site of Action.

PubMed

Froeba, Gebhard; Adolph, Oliver

2016-01-01

Xenon (Xe) in many respects is an ideal anaesthetic agent. Its blood/gas partition coefficient is lower than that of any other anaesthetic, enabling rapid induction of and emergence from anaesthesia. While the whole body kinetics during wash-in of inhalational anaesthesia is well known, data describing the pharmacokinetics of xenon in the cerebral compartment at the site of action are still largely missing. In order to illuminate xenon's cerebral pharmacokinetics, we anaesthetised five pigs and measured arterial, mixed- and sagittal sinus-venous blood, as well as end-expiratory gas concentrations of xenon by gas chromatography-mass spectrometry (GCMS) up to 30 minutes after starting the anaesthetic gas mixture. Despite xenon's fast onset of effect the half-time for equilibration between xenon concentration in arterial blood and at the site of action is measured to be 1.49 ± 0.04 minutes versus 3.91 ± 0.1 minutes. Successful loading of xenon in the brain during inhalational anesthesia was accomplished after approximately 15 minutes although the end-expiratory xenon concentration reached a plateau after 7 minutes. Thus cerebral xenon uptake rate is only moderate, xenon fast onset of action being largely due to its extremely fast alveolar uptake. To ensure safety and precise control during anaesthesia we need a profound knowledge about to what extent the measured end-tidal concentrations reflect the drug concentrations in the target tissue. The results of this study expand our knowledge about the temporal characteristics of xenon´s pharmacokinetics at its site of action and provide the basis for appropriate clinical protocols and experimental designs of future studies.

Ethylene Receptor 1 (ETR1) Is Sufficient and Has the Predominant Role in Mediating Inhibition of Ethylene Responses by Silver in Arabidopsis thaliana*

PubMed Central

McDaniel, Brittany K.; Binder, Brad M.

2012-01-01

Ethylene influences many processes in Arabidopsis thaliana through the action of five receptor isoforms. All five isoforms use copper as a cofactor for binding ethylene. Previous research showed that silver can substitute for copper as a cofactor for ethylene binding activity in the ETR1 ethylene receptor yet also inhibit ethylene responses in plants. End-point and rapid kinetic analyses of dark-grown seedling growth revealed that the effects of silver are mostly dependent upon ETR1, and ETR1 alone is sufficient for the effects of silver. Ethylene responses in etr1-6 etr2-3 ein4-4 triple mutants were not blocked by silver. Transformation of these triple mutants with cDNA for each receptor isoform under the promoter control of ETR1 revealed that the cETR1 transgene completely rescued responses to silver while the cETR2 transgene failed to rescue these responses. The other three isoforms partially rescued responses to silver. Ethylene binding assays on the binding domains of the five receptor isoforms expressed in yeast showed that silver supports ethylene binding to ETR1 and ERS1 but not the other isoforms. Thus, silver may have an effect on ethylene signaling outside of the ethylene binding pocket of the receptors. Ethylene binding to ETR1 with silver was ∼30% of binding with copper. However, alterations in the Kd for ethylene binding to ETR1 and the half-time of ethylene dissociation from ETR1 do not underlie this lower binding. Thus, it is likely that the lower ethylene binding activity of ETR1 with silver is due to fewer ethylene binding sites generated with silver versus copper. PMID:22692214

Gender affects renal vasoconstrictor response to Ang I and Ang II.

PubMed

Gandhi, S K; Gainer, J; King, D; Brown, N J

1998-01-01

This study tested the hypothesis that gender affects the pressor and renal vasoconstrictor responses to angiotensin (Ang) I and Ang II in salt-replete normotensive subjects. Ang I and Ang II were infused in graded doses into 9 men and 8 women in a randomized, single-blind, crossover study. There were no differences between genders in baseline blood pressure, heart rate, sodium excretion, renal plasma flow, angiotensin-converting enzyme (ACE) genotype, ACE activity, plasma renin activity, aldosterone, or Ang II levels. Although pressor responses to Ang I and Ang II were similar in men and women, there was a negative relationship between the change in mean arterial pressure and the change in heart rate during Ang I and II infusion in women only. The half-time of the pressor response after discontinuation of Ang I but not Ang II infusion was greater in men than in women (9.5+/-2.2 versus 4.3+/-2.1 minutes, P<.05). This difference in duration did not result from gender differences in the metabolism of Ang I because Ang II levels measured during Ang I infusion were identical in men and women. In contrast, the renal vasoconstrictor response to Ang I and Ang II was significantly increased in women compared with that in men (Ang I, -243+/-31 versus -138+/-13 U/1.73 m2; Ang II, -233+/-25 versus -175+/-18 U/1.73 m2; P<.03). These data suggest an effect of gender on baroreflex reactivity during angiotensin infusion. Moreover, in the setting of similar Ang II concentrations, the dramatic difference in the renal vasoconstrictor responses to Ang I and Ang II between salt-replete men and salt-replete women suggests gender differences at a pharmacodynamic level.

Spatial and temporal distributions of (134)Cs and (137)Cs derived from the TEPCO Fukushima Daiichi Nuclear Power Plant accident in the North Pacific Ocean by using optimal interpolation analysis.

PubMed

Inomata, Y; Aoyama, M; Tsubono, T; Tsumune, D; Hirose, K

2016-01-01

Optimal interpolation (OI) analysis was used to investigate the oceanic distributions of (134)Cs and (137)Cs released from the Tokyo Electric Power Company Fukushima Daiichi Nuclear Power Plant (FNPP1) accident. From the end of March to early April 2011, extremely high activities were observed in the coastal surface seawater near the FNPP1. The high activities spread to a region near 165°E in the western North Pacific Ocean, with a latitudinal center of 40°N. Atmospheric deposition also caused high activities in the region between 180° and 130°W in the North Pacific Ocean. The inventory of FNPP1-released (134)Cs in the North Pacific Ocean was estimated to be 15.3 ± 2.6 PBq. About half of this activity (8.4 ± 2.6 PBq) was found in the coastal region near the FNPP1. After 6 April 2011, when major direct releases ceased, the FNPP1-released (134)Cs in the coastal region decreased exponentially with an apparent half-time of about 4.2 ± 0.5 days and declined to about 2 ± 0.4 PBq by the middle of May 2011. Taking into account that the (134)Cs/(137)Cs activity ratio was about 1 just after release and was extremely uniform during the first month after the accident, the amount of (137)Cs released by the FNPP1 accident increased the North Pacific inventory of (137)Cs due to bomb testing during the 1950s and early 1960s by 20%.

Transfer of aged 239+240Pu, 238Pu, 241Am, and 137Cs to cattle grazing a contaminated arid environment.

PubMed

Gilbert, R O; Engel, D W; Anspaugh, L R

1989-09-01

In this paper, estimates are obtained of the fraction of ingested 239+240Pu, 238Pu, 241Am and 137Cs transferred to blood, muscle, liver, kidney, femur, vertebra, and gonads of a reproducing herd of 17 beef cattle, individuals of which grazed within fenced enclosures for up to 1064 days under natural conditions with no supplemental feeding at an arid site contaminated 16 years previously with transuranic radionuclides. The estimated geometric mean (GM) GI-to-blood fractional transfer of 238Pu (0.0001) was about 20 times larger than the estimated transfer of 239+240Pu (0.000005), while the estimated transfer of 241Am (0.00001) was about 2 times larger than that of 239+240Pu. These GM GI-to-blood transfers were smaller than the GI-to-blood transfer value of 0.001 recommended by the International Commission on Radiological Protection (ICRP) for humans exposed via food chains or occupationally from unknown mixtures or compounds of plutonium and americium. Statistical tests indicated significantly (p less than 0.05) larger GI-to-tissue transfers of (1) 238Pu as compared to 239+240Pu for all tissues examined, (2) of 238Pu as compared to 241Am for muscle, liver, femur, and vertebra, and (3) of 241Am as compared to 239+240Pu for blood serum, femur, and kidney. The estimated GM fractional transfers of 137Cs from GI to muscle and liver were 0.03 (n = 8) and 0.001 (n = 3), respectively, assuming a 50-day biological half-time of 137Cs in cattle tissue.

The Circular Hydraulic Jump in Microgravity

NASA Technical Reports Server (NTRS)

Avedisian, C. Thomas

1996-01-01

This report summarizes the key experimental results and observations that were obtained under NASA grant NAG 3-1627 from the Fluid Physics Program. The Principle Investigator was Thomas Avedisian. In addition a half-time post-doctoral associate, Ziqun Zhao, was funded for half year. The project monitor was David Chao of the NASA-Lewis Research Center in Cleveland, Ohio. The grant period was originally for one year at $34K and a no-cost extension was applied for and granted for an additional year. The research consisted of an experimental study of the circular hydraulic jump (CHJ) in microgravity using water as the working fluid. The evolution of the CHJ radius was measured during a sudden transition from normal to microgravity in a drop tower. The downstream height of the CHJ was controlled by submerging the target plate in a tank filled with water to the desired depth, and the measurements are compared with an existing theory for the location of the CHJ. Results show that the CHJ diameter is larger in microgravity than normal gravity. The adjustment of the CHJ diameter to a sudden change in gravity occurs over a period of about 200ms for the conditions of the present study, and remains constant thereafter for most of the flow conditions examined. For flow conditions that a CHJ was not first established at normal gravity but which later appeared during the transition tb microgravity, the CHJ diameter was not constant during the period of microgravity but continually changed. Good agreement between measured and predicted CHJ radii is found for normal gravity CHJ radii, but comparatively poorer agreement is observed for the CHJ radii measurements in microgravity.

Cardiomyopathy mutations in the tail of β-cardiac myosin modify the coiled-coil structure and affect integration into thick filaments in muscle sarcomeres in adult cardiomyocytes.

PubMed

Wolny, Marcin; Colegrave, Melanie; Colman, Lucy; White, Ed; Knight, Peter J; Peckham, Michelle

2013-11-01

It is unclear why mutations in the filament-forming tail of myosin heavy chain (MHC) cause hypertrophic or dilated cardiomyopathy as these mutations should not directly affect contraction. To investigate this, we first investigated the impact of five hypertrophic cardiomyopathy-causing (N1327K, E1356K, R1382W, E1555K, and R1768K) and one dilated cardiomyopathy-causing (R1500W) tail mutations on their ability to incorporate into muscle sarcomeres in vivo. We used adenoviral delivery to express full-length wild type or mutant enhanced GFP-MHC in isolated adult cardiomyocytes. Three mutations (N1327K, E1356K, and E1555K) reduced enhanced GFP-MHC incorporation into muscle sarcomeres, whereas the remainder had no effect. No mutations significantly affected contraction. Fluorescence recovery after photobleaching showed that fluorescence recovery for the mutation that incorporated least well (N1327K) was significantly faster than that of WT with half-times of 25.1 ± 1.8 and 32.2 ± 2.5 min (mean ± S.E.), respectively. Next, we determined the effects of each mutation on the helical properties of wild type and seven mutant peptides (7, 11, or 15 heptads long) from the myosin tail by circular dichroism. R1382W and E1768K slightly increased the α-helical nature of peptides. The remaining mutations reduced α-helical content, with N1327K showing the greatest reduction. Only peptides containing residues 1301-1329 were highly α-helical suggesting that this region helps in initiation of coiled coil. These results suggest that small effects of mutations on helicity translate into a reduced ability to incorporate into sarcomeres, which may elicit compensatory hypertrophy.

Bioinformatics analysis of single and multi-hybrid epitopes of GRA-1, GRA-4, GRA-6 and GRA-7 proteins to improve DNA vaccine design against Toxoplasma gondii.

PubMed

Shaddel, Minoo; Ebrahimi, Mansour; Tabandeh, Mohammad Reza

2018-06-01

Toxoplasma gondii , is a causative agent of morbidity and mortality in immunocompromised and congenitally-infected individuals. Attempts to construct DNA vaccines against T. gondii using surface proteins are increasing. The dense granule antigens are highly expressed in the acute and chronic phases of T. gondii infection and considered as suitable DNA vaccine candidates to control toxoplasmosis. In the present study, bioinformatics tools and online software were used to predict, analyze and compare the structural, physical and chemical characters and immunogenicity of the GRA-1, GRA-4, GRA-6 and GRA-7 proteins. Sequence alignment results indicated that the GRA-1, GRA-4, GRA-6 and GRA-7 proteins had low similarity. The secondary structure prediction demonstrated that among the four proteins, GRA-1 and GRA-6 had similar secondary structure except for a little discrepancy. Hydrophilicity/hydrophobicity analysis showed multiple hydrophilic regions and some classical high hydrophilic domains for each protein sequence. Immunogenic epitope prediction results demonstrated that the GRA-1 and GRA-4 epitopes were stable and GRA-4 showed the highest degree of antigenicity. Although the GRA-7 epitope had the highest score of immunogenicity, this epitope was instable and had the lowest degree of antigenicity and half-time in eukaryotic cell. Also, the results indicated that GRA4-GRA7 epitope and GRA6-GRA7 had the highest degree of antigenicity and immunogenicity among multi-hybrid epitopes, respectively. Totally, in the present study, single epitopes showed the highest degree of antigenicity compared with multi-hybrid epitopes. Given the results, it can be concluded that GRA-4 and GRA-7 can be powerful DNA vaccine candidates against T. gondii .

Clinical assessment of gastric emptying and sensory function utilizing gamma scintigraphy: Establishment of reference intervals for the liquid and solid components of the Nottingham test meal in healthy subjects.

PubMed

Parker, H L; Tucker, E; Blackshaw, E; Hoad, C L; Marciani, L; Perkins, A; Menne, D; Fox, M

2017-11-01

Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study presents the reference intervals of the modular "Nottingham test meal" (NTM) for assessment of gastric function by gamma scintigraphy (GSc) in a representative population of healthy volunteers (HVs) stratified for age and sex. The NTM comprises 400 mL liquid nutrient (0.75 kcal/mL) and an optional solid component (12 solid agar-beads (0 kcal). Filling and dyspeptic sensations were documented by 100 mm visual analogue scale (VAS). Gamma scintigraphy parameters that describe early and late phase Gastric emptying (GE) were calculated from validated models. Gastric emptying (GE) of the liquid component was measured in 73 HVs (male 34; aged 45±20). The NTM produced normal postprandial fullness (VAS ≥30 in 41/74 subjects). Dyspeptic symptoms were rare (VAS ≥30 in 2/74 subjects). Gastric emptying half-time with the Liquid- and Solid-component -NTM was median 44 (95% reference interval 28-78) minutes and 162 (144-193) minutes, respectively. Gastric accommodation was assessed by the ratio of the liquid-NTM retained in the proximal:total stomach and by Early phase emptying assessed by gastric volume after completing the meal (GCV0). No consistent effect of anthropometric measures on GE parameters was present. Reference intervals are presented for GSc measurements of gastric motor and sensory function assessed by the NTM. Studies involving patients are required to determine whether the reference interval range offers optimal diagnostic sensitivity and specificity. © 2017 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

Connectivity of the intracytoplasmic membrane of Rhodobacter sphaeroides: a functional approach.

PubMed

Verméglio, André; Lavergne, Jérôme; Rappaport, Fabrice

2016-01-01

The photosynthetic apparatus in the bacterium Rhodobacter sphaeroides is mostly present in intracytoplasmic membrane invaginations. It has long been debated whether these invaginations remain in topological continuity with the cytoplasmic membrane, or form isolated chromatophore vesicles. This issue is revisited here by functional approaches. The ionophore gramicidin was used as a probe of the relative size of the electro-osmotic units in isolated chromatophores, spheroplasts, or intact cells. The decay of the membrane potential was monitored from the electrochromic shift of carotenoids. The half-time of the decay induced by a single channel in intact cells was about 6 ms, thus three orders of magnitude slower than in isolated chromatophores. In spheroplasts obtained by lysis of the cell wall, the single channel decay was still slower (~23 ms) and the sensitivity toward the gramicidin concentration was enhanced 1,000-fold with respect to isolated chromatophores. These results indicate that the area of the functional membrane in cells or spheroplasts is about three orders of magnitude larger than that of isolated chromatophores. Intracytoplasmic vesicles, if present, could contribute to at most 10% of the photosynthetic apparatus in intact cells of Rba. sphaeroides. Similar conclusions were obtained from the effect of a ∆pH-induced diffusion potential in intact cells. This caused a large electrochromic response of carotenoids, of similar amplitude as the light-induced change, indicating that most of the system is sensitive to a pH change of the external medium. A single internal membrane and periplasmic space may offer significant advantages concerning renewal of the photosynthetic apparatus and reallocation of the components shared with other bioenergetic pathways.

Biopersistence of synthetic vitreous fibers and amosite asbestos in the rat lung following inhalation.

PubMed

Hesterberg, T W; Chase, G; Axten, C; Miller, W C; Musselman, R P; Kamstrup, O; Hadley, J; Morscheidt, C; Bernstein, D M; Thevenaz, P

1998-08-01

Fiber biopersistence as a major mechanism of fiber-induced pathogenicity was investigated. The lung biopersistence of 5 synthetic vitreous fibers (SVFs) and amosite asbestos was evaluated using the rat inhalation model. In contrast to several previous studies, this study examined fibers that dissolve relatively slowly in vitro at pH 7.4. Fisher rats were exposed for 5 days by nose-only inhalation to refractory ceramic fiber (RCF1a), rock (stone) wool (MMVF21), 2 relatively durable special application fiber glasses (MMVF32 or MMVF33), HT stonewool (MMVF34), amosite asbestos, or filtered air. Lung burdens were analyzed during 1 year post-exposure. Fiber aerosols contained 150-230 fibers/cc longer than 20 micrometer (>20 micrometer). On post-exposure Day 1, long-fiber lung burdens for the 6 test fibers were similar (12-16 x 10(5) fibers/lung >20 micrometer). After 1 year, the percentage of fibers >20 micrometer remaining in the lung was 0.04-10% for SVFs but 27% for amosite. Lung clearance weighted half-times (WT1/2) for fibers >20 micrometer were 6 days for MMVF34, 50-80 days for the other 4 SVFs, and >400 days for amosite. This study and 3 previous studies demonstrate a broad range of biopersistences for 19 different SVFs and 2 asbestos types. Ten of these fibers also have been (or are being) tested in chronic inhalation studies; in these studies, the very biopersistent fibers were carcinogenic (amosite, crocidolite, RCF1, MMVF32, and MMVF33), while the more rapidly clearing fibers were not (MMVF10, 11, 21, 22, and 34). These studies demonstrate the importance of biopersistence as an indicator of the potential pathogenicity of a wide range of fiber types. Copyright 1998 Academic Press.

Synthesis, Tribological and Hydrolysis Stability Study of Novel Benzotriazole Borate Derivative

PubMed Central

Liping, Xiong; Zhongyi, He; Liang, Qian; Lin, Mu; Aixi, Chen; Sheng, Han; Jianwei, Qiu; Xisheng, Fu

2014-01-01

Benzotriazole and borate derivatives have long been used as multifunctional additives to lubricants. A novel, environmentally friendly additive borate ester (NHB), which contains boron, ethanolamine, and benzotriazole groups in one molecule, was synthesized by a multi-step reaction, and its tribological properties in rapeseed oil (RSO) were investigated by a four-ball tribometer. The hydrolysis stability of the additive was investigated by half-time and open observation methods, and the mechanism of hydrolysis stability was discussed through Gaussian calculation. The novel compound NHB showed excellent performance under extreme pressure, against wearing, and in reducing friction, and its hydrolysis time is more than 1,220 times, which is better than that of triethyl borate. The mass ratio of NHB is bigger than that of the mixed liquid of triethyl borate and ethanolamine. The lone electron of amino N atoms forms a coordination effect with the B atom to compensate for the shortage of electrons in the B atom and to improve the hydrolysis stability of NHB. The surface morphology and the traces of different elements in the tribofilms formed with 1.0 wt.% NHB in were detected with scanning electron microscopy(SEM), energy dispersive X-ray spectroscopy (EDX)and X-ray photoelectron spectroscopy(XPS). The results shown that the additive caused a tribochemical reaction with the steel ball surface during the lubricating process. A mixed boundary lubrication film that contains organic nitrogen and inorganic salts, such as BN, B2O3, FeOx, Fe–O–B, and FeB, was also formed, and the formation of the lubricating film improved the tribological properties of the base oil. PMID:24465382

Chronic gonadotropin-releasing hormone inhibits activin induction of the ovine follicle-stimulating hormone beta-subunit: involvement of 3',5'-cyclic adenosine monophosphate response element binding protein and nitric oxide synthase type I.

PubMed

Shafiee-Kermani, Farideh; Han, Sang-oh; Miller, William L

2007-07-01

FSH is induced by activin, and this expression is modulated by GnRH through FSHB expression. This report focuses on the inhibitory effect of GnRH on activin-induced FSHB expression. Activin-treated primary murine pituitary cultures robustly express mutant ovine FSHBLuc-DeltaAP1, a luciferase transgene driven by 4.7 kb of ovine FSHB promoter. This promoter lacks two GnRH-inducible activator protein-1 sites, making it easier to observe GnRH-mediated inhibition. Luciferase expression from this transgene was decreased 94% by 100 nM GnRH with a half-time of approximately 4 h in pituitary cultures, and this inhibition was independent of follistatin. Activators of cAMP and protein kinase C like forskolin and phorbol 12-myristate 3-acetate (PMA), respectively, mimicked GnRH action. Kinetic studies of wild-type ovine FSHBLuc in LbetaT2 cells showed continuous induction by activin (4-fold) over 20 h. Most of this induction (78%) was blocked, beginning at 6 h. cAMP response element binding protein (CREB) was implicated in this inhibition because overexpression of its constitutively active mutant mimicked GnRH, and its inhibitor (inducible cAMP early repressor isoform II) reversed the inhibition caused by GnRH, forskolin, or PMA. In addition, GnRH, forskolin, or PMA increased the expression of a CREB-responsive reporter gene, 6xCRE-37PRL-Luc. Inhibition of nitric oxide type I (NOSI) by 7-nitroindazole also reversed GnRH-mediated inhibition by 60%. It is known that GnRH and CREB induce production of NOSI in gonadotropes and neuronal cells, respectively. These data support the concept that chronic GnRH inhibits activin-induced ovine FSHB expression by sequential activation of CREB and NOSI through the cAMP and/or protein kinase C pathways.

Response of the Oxygen Sensor NreB to Air In Vivo: Fe-S-Containing NreB and Apo-NreB in Aerobically and Anaerobically Growing Staphylococcus carnosus▿

PubMed Central

Reinhart, F.; Huber, A.; Thiele, R.; Unden, G.

2010-01-01

The sensor kinase NreB from Staphylococcus carnosus contains an O2-sensitive [4Fe-4S]2+ cluster which is converted by O2 to a [2Fe-2S]2+ cluster, followed by complete degradation and formation of Fe-S-less apo-NreB. NreB·[2Fe-2S]2+ and apoNreB are devoid of kinase activity. NreB contains four Cys residues which ligate the Fe-S clusters. The accessibility of the Cys residues to alkylating agents was tested and used to differentiate Fe-S-containing and Fe-S-less NreB. In a two-step labeling procedure, accessible Cys residues in the native protein were first labeled by iodoacetate. In the second step, Cys residues not labeled in the first step were alkylated with the fluorescent monobromobimane (mBBr) after denaturing of the protein. In purified (aerobic) apoNreB, most (96%) of the Cys residues were alkylated in the first step, but in anaerobic (Fe-S-containing) NreB only a small portion (23%) were alkylated. In anaerobic bacteria, a very small portion of the Cys residues of NreB (9%) were accessible to alkylation in the native state, whereas most (89%) of the Cys residues from aerobic bacteria were accessible. The change in accessibility allowed determination of the half-time (6 min) for the conversion of NreB·[4Fe-4S]2+ to apoNreB after the addition of air in vitro. Overall, in anaerobic bacteria most of the NreB exists as NreB·[4Fe-4S]2+, whereas in aerobic bacteria the (Fe-S-less) apoNreB is predominant and represents the physiological form. The number of accessible Cys residues was also determined by iodoacetate alkylation followed by mass spectrometry of Cys-containing peptides. The pattern of mass increases confirmed the results from the two-step labeling experiments. PMID:19854899

Human metabolism and excretion kinetics of aniline after a single oral dose.

PubMed

Modick, Hendrik; Weiss, Tobias; Dierkes, Georg; Koslitz, Stephan; Käfferlein, Heiko Udo; Brüning, Thomas; Koch, Holger Martin

2016-06-01

Aniline is an important source material in the chemical industry (e.g., rubber, pesticides, and pharmaceuticals). The general population is known to be ubiquitously exposed to aniline. Thus, assessment of aniline exposure is of both occupational and environmental relevance. Knowledge on human metabolism of aniline is scarce. We orally dosed four healthy male volunteers (two fast and two slow acetylators) with 5 mg isotope-labeled aniline, consecutively collected all urine samples over a period of 2 days, and investigated the renal excretion of aniline and its metabolites by LS-MS/MS and GC-MS. After enzymatic hydrolysis of glucuronide and sulfate conjugates, N-acetyl-4-aminophenol was the predominant urinary aniline metabolite representing 55.7-68.9 % of the oral dose, followed by the mercapturic acid conjugate of N-acetyl-4-aminophenol accounting for 2.5-6.1 %. Acetanilide and free aniline were found only in minor amounts accounting for 0.14-0.36 % of the dose. Overall, these four biomarkers excreted in urine over 48 h post-dose represented 62.4-72.1 % of the oral aniline dose. Elimination half-times were 3.4-4.3 h for N-acetyl-4-aminophenol, 4.1-5.5 h for the mercapturic acid conjugate, and 1.3-1.6 and 0.6-1.2 h for acetanilide and free aniline, respectively. Urinary maximum concentrations of N-acetyl-4-aminophenol were reached after about 4 h and maximum concentrations of the mercapturic acid conjugate after about 6 h, whereas concentrations of acetanilide and free aniline peaked after about 1 h. The present study is one of the first to provide reliable urinary excretion factors for aniline and its metabolites in humans after oral dosage, including data on the predominant urinary metabolite N-acetyl-4-aminophenol, also known as an analgesic under the name paracetamol/acetaminophen.

Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

PubMed

Kober, P M; Filkins, J P

1981-01-01

Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

Lower Intrinsic ADP-Stimulated Mitochondrial Respiration Underlies In Vivo Mitochondrial Dysfunction in Muscle of Male Type 2 Diabetic Patients

PubMed Central

Phielix, Esther; Schrauwen-Hinderling, Vera B.; Mensink, Marco; Lenaers, Ellen; Meex, Ruth; Hoeks, Joris; Kooi, Marianne Eline; Moonen-Kornips, Esther; Sels, Jean-Pierre; Hesselink, Matthijs K.C.; Schrauwen, Patrick

2008-01-01

OBJECTIVE—A lower in vivo mitochondrial function has been reported in both type 2 diabetic patients and first-degree relatives of type 2 diabetic patients. The nature of this reduction is unknown. Here, we tested the hypothesis that a lower intrinsic mitochondrial respiratory capacity may underlie lower in vivo mitochondrial function observed in diabetic patients. RESEARCH DESIGN AND METHODS—Ten overweight diabetic patients, 12 first-degree relatives, and 16 control subjects, all men, matched for age and BMI, participated in this study. Insulin sensitivity was measured with a hyperinsulinemic-euglycemic clamp. Ex vivo intrinsic mitochondrial respiratory capacity was determined in permeabilized skinned muscle fibers using high-resolution respirometry and normalized for mitochondrial content. In vivo mitochondrial function was determined by measuring phosphocreatine recovery half-time after exercise using 31P-magnetic resonance spectroscopy. RESULTS—Insulin-stimulated glucose disposal was lower in diabetic patients compared with control subjects (11.2 ± 2.8 vs. 28.9 ± 3.7 μmol · kg−1 fat-free mass · min−1, respectively; P = 0.003), with intermediate values for first-degree relatives (22.1 ± 3.4 μmol · kg−1 fat-free mass · min−1). In vivo mitochondrial function was 25% lower in diabetic patients (P = 0.034) and 23% lower in first-degree relatives, but the latter did not reach statistical significance (P = 0.08). Interestingly, ADP-stimulated basal respiration was 35% lower in diabetic patients (P = 0.031), and fluoro-carbonyl cyanide phenylhydrazone–driven maximal mitochondrial respiratory capacity was 31% lower in diabetic patients (P = 0.05) compared with control subjects with intermediate values for first-degree relatives. CONCLUSIONS—A reduced basal ADP-stimulated and maximal mitochondrial respiratory capacity underlies the reduction in in vivo mitochondrial function, independent of mitochondrial content. A reduced capacity at both the level of the electron transport chain and phosphorylation system underlies this impaired mitochondrial capacity. PMID:18678616

Nickel absorption and kinetics in human volunteers.

PubMed

Sunderman, F W; Hopfer, S M; Sweeney, K R; Marcus, A H; Most, B M; Creason, J

1989-05-01

Mathematical modeling of the kinetics of nickel absorption, distribution, and elimination was performed in healthy human volunteers who ingested NiSO4 drinking water (Experiment 1) or added to food (Experiment 2). Nickel was analyzed by electrothermal atomic absorption spectrophotometry in serum, urine, and feces collected during 2 days before and 4 days after a specified NiSO4 dose (12 micrograms of nickel/kg, n = 4; 18 micrograms of nickel/kg, n = 4; or 50 micrograms of nickel/kg, n = 1). In Experiment 1, each of the subjects fasted 12 hr before and 3 hr after drinking one of the specified NiSO4 doses dissolved in water; in Experiment 2, the respective subjects fasted 12 hr before consuming a standard American breakfast that contained the identical dose of NiSO4 added to scrambled eggs. Kinetic analyses, using a compartmental model, provided excellent goodness-of-fit for paired data sets from all subjects. Absorbed nickel averaged 27 +/- 17% (mean +/- SD) of the dose ingested in water vs 0.7 +/- 0.4% of the same dose ingested in food (a 40-fold difference); rate constants for nickel absorption, transfer, and elimination were not significantly influenced by the oral vehicle. The elimination half-time for absorbed nickel averaged 28 +/- 9 hr. Renal clearance of nickel averaged 8.3 +/- 2.0 ml/min/1.73 m2 in Experiment 1 and 5.8 +/- 4.3 ml/min/1.73 m2 in Experiment 2. This study confirms that dietary constituents profoundly reduce the bioavailability of Ni2+ for alimentary absorption; approximately one-quarter of nickel ingested in drinking water after an over-night fast is absorbed from the human intestine and excreted in urine, compared with only 1% of nickel ingested in food. The compartmental model and kinetic parameters provided by this study will reduce the uncertainty of toxicologic risk assessments of human exposures to nickel in drinking water and food.

The Extended Oxygen Window Concept for Programming Saturation Decompressions Using Air and Nitrox

PubMed Central

Kot, Jacek; Sicko, Zdzislaw

2015-01-01

Saturation decompression is a physiological process of transition from one steady state, full saturation with inert gas at pressure, to another one: standard conditions at surface. It is defined by the borderline condition for time spent at a particular depth (pressure) and inert gas in the breathing mixture (nitrogen, helium). It is a delicate and long lasting process during which single milliliters of inert gas are eliminated every minute, and any disturbance can lead to the creation of gas bubbles leading to decompression sickness (DCS). Most operational procedures rely on experimentally found parameters describing a continuous slow decompression rate. In Poland, the system for programming of continuous decompression after saturation with compressed air and nitrox has been developed as based on the concept of the Extended Oxygen Window (EOW). EOW mainly depends on the physiology of the metabolic oxygen window—also called inherent unsaturation or partial pressure vacancy—but also on metabolism of carbon dioxide, the existence of water vapor, as well as tissue tension. Initially, ambient pressure can be reduced at a higher rate allowing the elimination of inert gas from faster compartments using the EOW concept, and maximum outflow of nitrogen. Then, keeping a driving force for long decompression not exceeding the EOW allows optimal elimination of nitrogen from the limiting compartment with half-time of 360 min. The model has been theoretically verified through its application for estimation of risk of decompression sickness in published systems of air and nitrox saturation decompressions, where DCS cases were observed. Clear dose-reaction relation exists, and this confirms that any supersaturation over the EOW creates a risk for DCS. Using the concept of the EOW, 76 man-decompressions were conducted after air and nitrox saturations in depth range between 18 and 45 meters with no single case of DCS. In summary, the EOW concept describes physiology of decompression after saturation with nitrogen-based breathing mixtures. PMID:26111113

Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways

PubMed Central

Botolin, Daniela; Wang, Yun; Christian, Barbara; Jump, Donald B.

2009-01-01

Insulin induces and dietary n-3 PUFAs suppress hepatic de novo lipogenesis by controlling sterol-regulatory element binding protein-1 nuclear abundance (nSREBP-1). Our goal was to define the mechanisms involved in this regulatory process. Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 and mRNASREBP-1c while suppressing mRNAInsig-2 but not mRNAInsig-1. These events are preceded by rapid but transient increases in Akt and Erk phosphorylation. Removal of insulin from hepatocytes leads to a rapid decline in nSREBP-1 [half-time (T1/2) ~ 10 h] that is abrogated by inhibitors of 26S proteasomal degradation. 22:6,n-3, the major n-3 PUFA accumulating in livers of fish oil-fed rats, suppresses hepatocyte levels of nSREBP-1, mRNASREBP-1c, and mRNAInsig-2 but modestly and transiently induces mRNAInsig-1. More importantly, 22:6,n-3 accelerates the disappearance of hepatocyte nSREBP-1 (T1/2 ~ 4 h) through a 26S proteasome-dependent process. 22:6,n-3 has minimal effects on microsomal SREBP-1 and sterol-regulatory element binding protein cleavage-activating protein or nuclear SREBP-2. 22:6,n-3 transiently inhibits insulin-induced Akt phosphorylation but induces Erk phosphorylation. Inhibitors of Erk phosphorylation, but not overexpressed constitutively active Akt, rapidly attenuate 22:6,n-3 suppression of nSREBP-1. Thus, 22:6,n-3 suppresses hepatocyte nSREBP-1 through 26S proteasome- and Erk-dependent pathways. These studies reveal a novel mechanism for n-3 PUFA regulation of hepatocyte nSREBP-1 and lipid metabolism.—Botolin, D., Y. Wang, B. Christian, and D. B. Jump. Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways. PMID:16222032

Repair of radiation-induced heat-labile sites is independent of DNA-PKcs, XRCC1 or PARP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenerlöw, Bo; Karlsson, Karin H.; Radulescu, Irina

2008-04-29

Ionizing radiation induces a variety of different DNA lesions: in addition to the most critical DNA damage, the DSB, numerous base alterations, SSBs and other modifications of the DNA double-helix are formed. When several non-DSB lesions are clustered within a short distance along DNA, or close to a DSB, they may interfere with the repair of DSBs and affect the measurement of DSB induction and repair. We have previously shown that a substantial fraction of DSBs measured by pulsed-field gel electrophoresis (PFGE) are in fact due to heat-labile sites (HLS) within clustered lesions, thus reflecting an artifact of preparation ofmore » genomic DNA at elevated temperature. To further characterize the influence of HLS on DSB induction and repair, four human cell lines (GM5758, GM7166, M059K, U-1810) with apparently normal DSB rejoining were tested for bi-phasic rejoining after gamma irradiation. When heat-released DSBs were excluded from the measurements the fraction of fast rejoining decreased to less than 50% of the total. However, neither the half-times of the fast (t{sub 1/2} = 7-8 min) or slow (t{sub 1/2} = 2.5 h) DSB rejoining were changed significantly. At t=0 the heat-released DSBs accounted for almost 40% of the DSBs, corresponding to 10 extra DSB/cell/Gy in the initial DSB yield. These heat-released DSBs were repaired within 60-90 min in all tested cells, including M059K cells treated with wortmannin or DNA-PKcs defect M059J cells. Furthermore, cells lacking XRCC1 or Poly(ADP-ribose) polymerase-1 (PARP-1) rejoined both total DSBs and heat-released DSBs similar to normal cells. In summary, the presence of heat-labile sites have a substantial impact on DSB induction yields and DSB rejoining rates measured by pulsed-field gel electrophoresis, and HLS repair is independent of DNA-PKcs, XRCC1 and PARP.« less

LONG-TERM DYNAMICS OF RADIONUCLIDE VERTICAL MIGRATION IN SOILS OF THE CHERNOBYL NUCLEAR POWER PLANT EXCLUSION ZONE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farfan, E

2009-11-19

The radioactive fallout from the Chernobyl Nuclear Power Plant (ChNPP) accident consisted of fuel and condensation components. An important radioecological task associated with the late phase of the accident is to evaluate the dynamics of radionuclide mobility in soils. Identification of the variability (or invariability) in the radionuclide transfer parameters makes it possible to (1) accurately predict migration patterns and biological availability of radionuclides and (2) evaluate long-term exposure trends for the population who may reoccupy the remediated abandoned areas. In 1986-1987, a number of experimental plots were established within various tracts of the fallout plume to assist with themore » determination of the long-term dynamics of radionuclide vertical migration in the soils. The transfer parameters for {sup 137}Cs, {sup 90}Sr, and {sup 239,240}Pu in the soil profile, as well as their ecological half-time of the radionuclide residence (T{sub 1/2}{sup ecol}) values in the upper 5-cm thick soil layers of different grasslands were estimated at various times since the accident. Migration characteristics in the grassland soils tend to decrease as follows: {sup 90}Sr > {sup 137}Cs {ge} {sup 239,240}Pu. It was found that the {sup 137}Cs absolute T{sub 1/2}{sup ecol} values are 3-7 times higher than its radioactive decay half-life value. Therefore, changes in the exposure dose resulting from the soil deposited {sup 137}Cs now depend only on its radioactive decay. The {sup 90}Sr T{sub 1/2}{sup ecol} values for the 21st year after the fallout tend to decrease, indicating an intensification of its migration capabilities. This trend appears consistent with a pool of mobile {sup 90}Sr forms that grows over time due to destruction of the fuel particles.« less

The influence of a 12% carbohydrate-electrolyte beverage on self-paced soccer-specific exercise performance.

PubMed

Harper, Liam D; Stevenson, Emma J; Rollo, Ian; Russell, Mark

2017-12-01

To assess the physiological and performance effects of a 12% carbohydrate-electrolyte beverage consumed at practically applicable time-points (i.e., before each half) throughout simulated soccer match-play. Randomised, counterbalanced, crossover. Fed players (n=15) performed 90-min of soccer-specific exercise (including self-paced exercise at the end of each half). Players consumed carbohydrate-electrolyte (CHO; 60g×500ml -1 , Na + 205mg×500ml -1 ), placebo-electrolyte (PL) or water (Wat) beverages at the end of the warm-up (250ml) and half-time (250ml plus ad-libitum water). Blood was drawn before each half and every 15-min during exercise. Physical (15-m sprinting, countermovement jumps, self-paced distance, acceleration/deceleration count), technical (dribbling) and cognitive (memory, attention, decision-making) performance was assessed. Ratings of perceived exertion (RPE) and abdominal discomfort were measured. Against Wat and PL, CHO increased (all p<0.05) mean accelerations >1.5m·s -2 during self-paced exercise (>+25%) and dribbling speed from 60-min onwards (>+3%). Mean sprinting speed improved (+2.7%) in CHO versus Wat. Blood glucose increased before and during each half in CHO versus PL and Wat (all p<0.05). A 27% decline in glycaemia occurred at 60-min in CHO. RPE was comparable between trials. Cognition reduced post-exercise (p<0.05); this decline was not attenuated by CHO. Abdominal discomfort increased during exercise but was similar between trials. Using more realistic fluid ingestion timings than have been examined previously, consuming a 12% carbohydrate-electrolyte beverage increased blood glucose, self-paced exercise performance, and improved dribbling speed in the final 30-min of exercise compared to water and placebo. Carbohydrates did not attenuate post-exercise reductions in cognition. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Transport across the Blood-Brain Barrier of Pluronic Leptin

PubMed Central

Price, Tulin O.; Farr, Susan A.; Yi, Xiang; Vinogradov, Serguei; Batrakova, Elena; Kabanov, Alexander V.

2010-01-01

Leptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity. Chemical modification of polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) is a promising technology to improve efficiency of delivery of polypeptides to the brain. In the present study, we determined the effects of Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance, stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when injected intracerebroventricularly after overnight food deprivation and 125I-leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain unidirectional influx rate (Ki) = 0.272 ± 0.037 μl/g · min] by a nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was administered via tail vein in normal body weight mice [0–30 min, p < 0.0005; 0–2 h, p < 0.001]. These studies show that the structure based Pluronic modification of leptin increased metabolic stability, reduced food intake, and allowed BBB penetration by a mechanism-independent BBB leptin transporter. PMID:20053933

Proteomic profiling reveals DNA damage, nucleolar and ribosomal stress are the main responses to oxaliplatin treatment in cancer cells.

PubMed

Ozdian, Tomas; Holub, Dusan; Maceckova, Zuzana; Varanasi, Lakshman; Rylova, Gabriela; Rehulka, Jiri; Vaclavkova, Jana; Slavik, Hanus; Moudry, Pavel; Znojek, Pawel; Stankova, Jarmila; de Sanctis, Juan Bautista; Hajduch, Marian; Dzubak, Petr

2017-06-06

Oxaliplatin is widely used to treat colorectal cancer in both palliative and adjuvant settings. It is also being tested for use in treating hematological, esophageal, biliary tract, pancreatic, gastric, and hepatocellular cancers. Despite its routine clinical use, little is known about the responses it induces in cancer cells. Therefore the whole-cell proteomics study was conducted to characterize the cellular response induced by oxaliplatin. Chemosensitive CCRF-CEM cells were treated with oxaliplatin at 29.3μM (5×IC 50 ) for 240min (half-time to caspase activation). The proteomes of un-/treated cells were then compared by high-resolution mass spectrometry, revealing 4049 proteins expressed over 3 biological replicates. Among these proteins, 76 were significantly downregulated and 31 significantly upregulated in at least two replicates. In agreement with the DNA-damaging effects of platinum drugs, proteins involved in DNA damage responses were present in both the upregulated and downregulated groups. The downregulated proteins were divided into three subgroups; i) centrosomal proteins, ii) RNA processing and iii) ribosomal proteins, which indicates nucleolar and ribosomal stress. In conclusion, our data supported by further validation experiments indicate the initial cellular response to oxaliplatin is the activation of DNA damage response, which in turn or in parallel triggers nucleolar and ribosomal stress. We have performed a whole-cell proteomic study of cellular response to oxaliplatin treatment, which is the drug predominantly used in the treatment of colorectal cancer. Compared to its predecessors, cisplatin and carboplatin, there is only a small fraction of studies dedicated to oxaliplatin. From those studies, most of them are focused on modification of treatment regimens or study of oxaliplatin in new cancer diagnoses. Cellular response hasn't been studied deeply and to our best knowledge, this is the first whole-cell proteomics study focused exclusively to this important topic, which can help to understand molecular mechanisms of action. Copyright © 2017 Elsevier B.V. All rights reserved.

Three-dimensional proximal flow convergence automatic calculation for determining mitral valve area in rheumatic mitral stenosis.

PubMed

Sampaio, Francisco; Ladeiras-Lopes, Ricardo; Almeida, João; Fonseca, Paulo; Fontes-Carvalho, Ricardo; Ribeiro, José; Gama, Vasco

2017-07-01

Management of patients with mitral stenosis (MS) depends heavily on the accurate quantification of mitral valve area (MVA) using echocardiography. All currently used two-dimensional (2D) methods have limitations. Estimation of MVA using the proximal isovelocity surface area (PISA) method with real time three-dimensional (3D) echocardiography may circumvent those limitations. We aimed to evaluate the accuracy of 3D direct measurement of PISA in the estimation of MVA. Twenty-seven consecutive patients (median age of 63 years; 77.8% females) with rheumatic MS were prospectively studied. Transthoracic and transesophageal echocardiography with 2D and 3D acquisitions were performed on the same day. The reference method for MVA quantification was valve planimetry after 3D-volume multiplanar reconstruction. A semi-automated software was used to calculate the 3D flow convergence volume. Compared to MVA estimation using 3D planimetry, 3D PISA showed the best correlation (rho=0.78, P<.0001), followed by pressure half-time (PHT: rho=0.66, P<.001), continuity equation (CE: rho=0.61, P=.003), and 2D PISA (rho=0.26, P=.203). Bland-Altman analysis revealed a good agreement for MVA estimation with 3D PISA (mean difference -0.03 cm 2 ; limits of agreement (LOA) -0.40-0.35), in contrast to wider LOA for 2D methods: CE (mean difference 0.02 cm 2 , LOA -0.56-0.60); PHT (mean difference 0.31 cm 2 , LOA -0.32-0.95); 2D PISA (mean difference -0.03 cm 2 , LOA -0.92-0.86). MVA estimation using 3D PISA was feasible and more accurate than 2D methods. Its introduction in daily clinical practice seems possible and may overcome technical limitations of 2D methods. © 2017, Wiley Periodicals, Inc.

Strategies for Growth in a Young Earth Sciences Department

NASA Astrophysics Data System (ADS)

Clement, B. M.; Hickey-Vargas, R.; Draper, G.

2005-12-01

The Department of Earth Sciences at Florida International University (FIU) has been fortunate to be part of a rapidly growing university. FIU began offering classes in 1972 with an initial enrollment of 5600 students, and today enrollment exceeds 35,000 students. During this time the Department of Earth Sciences has grown to a faculty of 14 and offers the BA, BS, MS and PhD degrees. Our department, however, has faced the same challenges meeting many Earth Science departments in that our number of undergraduate majors has not grown at the same pace as the university enrollment (or at the same pace as enrollment in our graduate program). Two strategies have proven effective and have helped the department build its program in spite of this challenge. The first strategy was to create tenure-track positions with a 50% assignment in the Earth Sciences Department and 50% in a research center on campus. We currently have two faculty who have half-time appointments in the Southeast Environmental Research Center, and we have a new faculty member joining in the Spring who will have a joint appointment with the International Hurricane Research Center. This strategy has made it possible to gain expertise in, and to offer courses in, critical areas (such as hydrogeology and meteorology) that we otherwise would not be able to offer. The second strategy is to develop strong courses for non-majors that satisfy FIU's University Common Curriculum requirements. A particularly successful example is a new course titled "The History of Life". This course was designed to take advantage of our existing expertise in paleobiology, and offer a class that satisfies the University Common Curriculum requirement that every student take a laboratory course in the life sciences. This class now fills to capacity each semester with more than 200 students. This course not only boosts our department's productivity, but it lets us reach 200 new students each semester with many potential new Earth Science majors among them.

Kinetics and dynamics of annealing during sub-gel phase formation in phospholipid bilayers

PubMed Central

Páli, Tibor; Bartucci, Rosa; Horváth, László I.; Marsh, Derek

1993-01-01

The saturation transfer electron spin resonance (STESR) spectra of spin-labeled phosphatidylcholine have been used to follow the kinetics of conversion from the gel phase to the sub-gel phase in aqueous bilayers of dipalmitoyl phosphatidylcholine. This is a simple, well-defined model system for lipid domain formation in membranes. The integrated intensity of the STESR spectrum from the chain-labeled lipid first increases and then decreases with time of incubation in the gel phase at 0°C. The first, more rapid phase of the kinetics is attributed to the conversion of germ nuclei to growth nuclei of the sub-gel phase. The increase in STESR intensity corresponds to the reduction in chain mobility of spin labels located in the gel phase at the boundaries of the growth nuclei and correlates with the increase in the diagnostic STESR line height ratios over this time range. The second, slower phase of the kinetics is attributed to growth of the domains of the sub-gel phase. The decrease in STESR intensity over this time regime corresponds to exclusion of the spin-labeled lipids from the tightly packed sub-gel phase and correlates quantitatively with calibrations of the spin label concentration dependence of the STESR intensity in the gel phase. The kinetics of formation of the sub-gel phase are consistent with the classical model for domain formation and growth. At 0°C, the half-time for conversion of germ nuclei to growth nuclei is ∼7.7 h and domain growth of the sub-gel phase is characterized by a rate constant of 0.025 h-1. The temperature dependence of the STESR spectra from samples annealed at 0°C suggests that the subtransition takes place via dissolution of sub-gel phase domains, possibly accompanied by domain fission. PMID:19431899

The pH-dependent rate of action of local anesthetics on the node of Ranvier

PubMed Central

1977-01-01

Local anesthetic solutions were applied suddenly to the outside of single myelinated nerve fibers to measure the time course of development of block of sodium channels. Sodium currents were measured under voltage clamp with test pulses applied several times per second during the solution change. The rate of block was studied by using drugs of different lipid solubility and of different charge type, and the external pH was varied from pH 8.3 to pH 6 to change the degree of ionization of the amine compounds. At pH 8.3 the half-time of action of amine anesthetics such as lidocaine, procaine, tetracaine, and others was always less than 2 s and usually less than 1 s. Lowering the pH to 6.0 decreased the apparent potency and slowed the rate of action of these drugs. The rate of action of neutral benzocaine was fast (1 s) and pH independent. The rate of action of cationic quaternary QX-572 was slow (greater than 200 s) and also pH independent. Other quaternary anesthetic derivatives showed no action when applied outside. The result is that neutral drug forms act much more rapidly than charged ones, suggesting that externally applied local anesthetics must cross a hydrophobic barrier to reach their receptor. A model representing diffusion of drug into the nerve fiber gives reasonable time courses of action and reasonable membrane permeability coefficients on the assumption that the hydrophobic barrier is the nodal membrane. Arguments are given that there may be a need for reinterpretation of many published experiments on the location of the anesthetic receptor and on which charge form of the drug is active to take into account the effects of unstirred layers, high membrane permeability, and high lipid solubility. PMID:16078

Sorting of endocytosed transferrin and asialoglycoprotein occurs immediately after internalization in HepG2 cells

PubMed Central

1987-01-01

After receptor-mediated uptake, asialoglycoproteins are routed to lysosomes, while transferrin is returned to the medium as apotransferrin. This sorting process was analyzed using 3,3'- diaminobenzidine (DAB) cytochemistry, followed by Percoll density gradient cell fractionation. A conjugate of asialoorosomucoid (ASOR) and horseradish peroxidase (HRP) was used as a ligand for the asialoglycoprotein receptor. Cells were incubated at 0 degree C in the presence of both 131I-transferrin and 125I-ASOR/HRP. Endocytosis of prebound 125I-ASOR/HRP and 131I-transferrin was monitored by cell fractionation on Percoll density gradients. Incubation of the cell homogenate in the presence of DAB and H2O2 before cell fractionation gave rise to a density shift of 125I-ASOR/HRP-containing vesicles due to HRP-catalyzed DAB polymerization. An identical change in density for 125I-transferrin and 125I-ASOR/HRP, induced by DAB cytochemistry, is taken as evidence for the concomitant presence of both ligands in the same compartment. At 37 degrees C, sorting of the two ligands occurred with a half-time of approximately 2 min, and was nearly completed within 10 min. The 125I-ASOR/HRP-induced shift of 131I-transferrin was completely dependent on the receptor-mediated uptake of 125I-ASOR/HRP in the same compartment. In the presence of a weak base (0.3 mM primaquine), the recycling of transferrin receptors was blocked. The cell surface transferrin receptor population was decreased within 6 min to 15% of its original size. DAB cytochemistry showed that sorting between endocytosed 131I-transferrin and 125I-ASOR/HRP was also blocked in the presence of primaquine. These results indicate that transferrin and asialoglycoprotein are taken up via the same compartments and that segregation of the transferrin-receptor complex and asialoglycoprotein occurs very efficiently soon after uptake. PMID:3032986

Novel Mechanism for Regulation of Epidermal Growth Factor Receptor Endocytosis Revealed by Protein Kinase A Inhibition

PubMed Central

Salazar, Gloria; González, Alfonso

2002-01-01

Current models put forward that the epidermal growth factor receptor (EGFR) is efficiently internalized via clathrin-coated pits only in response to ligand-induced activation of its intrinsic tyrosine kinase and is subsequently directed into a lysosomal-proteasomal degradation pathway by mechanisms that include receptor tyrosine phosphorylation and ubiquitylation. Herein, we report a novel mechanism of EGFR internalization that does not require ligand binding, receptor kinase activity, or ubiquitylation and does not direct the receptor into a degradative pathway. Inhibition of basal protein kinase A (PKA) activity by H89 and the cell-permeable substrate peptide Myr-PKI induced internalization of 40–60% unoccupied, inactive EGFR, and its accumulation into early endosomes without affecting endocytosis of transferrin and μ-opioid receptors. This effect was abrogated by interfering with clathrin function. Thus, the predominant distribution of inactive EGFR at the plasma membrane is not simply by default but involves a PKA-dependent restrictive condition resulting in receptor avoidance of endocytosis until it is stimulated by ligand. Furthermore, PKA inhibition may contribute to ligand-induced EGFR endocytosis because epidermal growth factor inhibited 26% of PKA basal activity. On the other hand, H89 did not alter ligand-induced internalization of EGFR but doubled its half-time of down-regulation by retarding its segregation into degradative compartments, seemingly due to a delay in the receptor tyrosine phosphorylation and ubiquitylation. Our results reveal that PKA basal activity controls EGFR function at two levels: 1) residence time of inactive EGFR at the cell surface by a process of “endocytic evasion,” modulating the accessibility of receptors to stimuli; and 2) sorting events leading to the down-regulation pathway of ligand-activated EGFR, determining the length of its intracellular signaling. They add a new dimension to the fine-tuning of EGFR function in response to cellular demands and cross talk with other signaling receptors. PMID:12006662

Triptolide inhibits transcription of hTERT through down-regulation of transcription factor specificity protein 1 in primary effusion lymphoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Long, Cong; Wang, Jingchao; Guo, Wei

Primary effusion lymphoma (PEL) is a rare and aggressive non-Hodgkin's lymphoma. Human telomerase reverse transcriptase (hTERT), a key component responsible for the regulation of telomerase activity, plays important roles in cellular immortalization and cancer development. Triptolide purified from Tripterygium extracts displays a broad-spectrum bioactivity profile, including immunosuppressive, anti-inflammatory, and anti-tumor. In this study, it is investigated whether triptolide reduces hTERT expression and suppresses its activity in PEL cells. The mRNA and protein levels of hTERT were examined by real time-PCR and Western blotting, respectively. The activity of hTERT promoter was determined by Dual luciferase reporter assay. Our results demonstrated thatmore » triptolide decreased expression of hTERT at both mRNA and protein levels. Further gene sequence analysis indicated that the activity of hTERT promoter was suppressed by triptolide. Triptolide also reduced the half-time of hTERT. Additionally, triptolide inhibited the expression of transcription factor specificity protein 1(Sp1) in PEL cells. Furthermore, knock-down of Sp1 by using specific shRNAs resulted in down-regulation of hTERT transcription and protein expression levels. Inhibition of Sp1 by specific shRNAs enhanced triptolide-induced cell growth inhibition and apoptosis. Collectively, our results demonstrate that the inhibitory effect of triptolide on hTERT transcription is possibly mediated by inhibition of transcription factor Sp1 in PEL cells. - Highlights: • Triptolide reduces expression of hTERT by decreasing its transcription level. • Triptolide reduces promoter activity and stability of hTERT. • Triptolide down-regulates expression of Sp1. • Special Sp1 shRNAs inhibit transcription and protein expression of hTERT. • Triptolide and Sp1 shRNA2 induce cell proliferation inhibition and apoptosis.« less

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

PubMed

Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

2017-06-01

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-E-T-385: 4D Radiobiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fourkal, E; Hossain, M; Veltchev, I

2014-06-01

Purpose: The linear-quadratic model is the most prevalent model for planning dose fractionation in radiation therapy in the low dose per fraction regimens. However for high-dose fractions, used in SRS/SBRT/HDR treatments the LQ model does not yield accurate predictions, due to neglecting the reduction in the number of sublethal lesions as a result of their conversion to lethal lesions with subsequent irradiation. Proper accounting for this reduction in the number of sublethally damaged lesions leads to the dependence of the survival fraction on the temporal structure of the dose. The main objective of this work is to show that themore » functional dependence of the dose rate on time in each voxel is an important additional factor that can significantly influence the TCP. Methods: Two SBRT lung plans have been used to calculate the TCPs for the same patient. One plan is a 3D conformal plan and the other is an IMRT plan. Both plans are normalized so that 99.5% of PTV volume receives the same prescription dose of 50 Gy in 5 fractions. The dose rate in each individual voxel is calculated as a function of treatment time and subsequently used in the calculation of TCP. Results: The calculated TCPs show that shorter delivery times lead to greater TCP, despite all delivery times being short compared to the repair half-time for sublethal lesions. Furthermore, calculated TCP(IMRT) =0.308 for the IMRT plan is smaller than TCP(3D) =0.425 for 3D conformal, even though it shows greater tumor hot spots and equal PTV coverage. The calculated TCPs are considerably lower compared to those based on the LQ model for which TCP=1 for both plans. Conclusion: The functional dependence of the voxel-by-voxel dose rate on time may be an important factor in predicting the treatment outcome and cannot be neglected in radiobiological modeling.« less

Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

PubMed

Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

1986-02-12

Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase-induced removal of cellular cholesterol.

The time-course of red blood cell intracellular pH recovery following short-circuiting in relation to venous transit times in rainbow trout, Oncorhynchus mykiss.

PubMed

Harter, Till Sebastian; May, Alexandra G; Federspiel, William J; Supuran, Claudiu T; Brauner, Colin J

2018-04-11

Accumulating evidence is highlighting the importance of a system of enhanced hemoglobin-oxygen (Hb-O 2 ) unloading for cardiovascular O 2 transport in teleosts. Adrenergically stimulated sodium-proton-exchangers (β-NHE) create H + gradients across the red blood cell (RBC) membrane that are short-circuited in the presence of plasma-accessible carbonic anhydrase (paCA) at the tissues; the result is a large arterial-venous pH shift that greatly enhances O 2 unloading from pH-sensitive Hb. However, RBC intracellular pH (pH i ) must recover during venous transit (31-90 s), to enable O 2 -loading at the gills. The halftimes (t 1/2 ) and magnitudes of RBC β-adrenergic stimulation, short-circuiting with paCA and recovery of RBC pH i , were assessed in vitro, on rainbow trout whole blood, and using changes in closed-system PO 2 as a sensitive indicator for changes in RBC pH i . In addition, the recovery rate of RBC pH i was assessed in a continuous-flow apparatus that more closely mimics RBC transit though the circulation. Results indicate that: i) the t 1/2 of CA short-circuiting is likely within the residence time of blood in the capillaries; ii) the t 1/2 of RBC pH i recovery is 17 s and within the time of RBC venous transit; and iii) after short-circuiting RBCs re-establish the initial H + gradient across the membrane and can potentially undergo repeated cycles of short-circuiting and recovery. Thus, teleosts have evolved a system that greatly enhances O 2 unloading from pH-sensitive Hb at the tissues, while protecting O 2 loading at the gills; the resulting increase in O 2 transport per unit of blood flow may enable the tremendous athletic ability of salmonids.

RELATIONSHIP BETWEEN GLYCEMIC CONTROL AND GASTRIC EMPTYING IN POORLY CONTROLLED TYPE 2 DIABETES

PubMed Central

Bharucha, Adil E.; Kudva, Yogish; Basu, Ananda; Camilleri, Michael; Low, Phillip A.; Vella, Adrian; Zinsmeister, Alan R.

2014-01-01

Background & Aims Acute hyperglycemia delays gastric emptying in patients with diabetes. However, it is not clear whether improved control of glycemia affects gastric emptying in these patients. We investigated whether overnight and short-term (6 months) improvements in control of glycemia affect gastric emptying. Methods We studied 30 patients with poorly controlled type 2 diabetes (levels of glycated hemoglobin >9%). We measured gastric emptying using the [13C]-spirulina platensis breath test on the patients’ first visit (visit 1), after overnight administration of insulin or saline, 1 week later (visit 2), and 6 months after intensive therapy for diabetes. We also measured fasting and post-prandial plasma levels of C-peptide, GLP1, and amylin, as well as autonomic functions. Results At visit 1, gastric emptying was normal in 10 patients, delayed in 14, and accelerated in 6; 6 patients had gastrointestinal symptoms; vagal dysfunction was associated with delayed gastric emptying (P<.05). Higher fasting blood levels of glucose were associated with shorter half-times of gastric emptying (thalf) at visits 1 (r= −0.46, P=.01) and 2 (r= −0.43, P=.02). Although blood levels of glucose were lower after administration of insulin (132±7 mg/dl) than saline (211±15 mg/dl; P=0.0002), gastric emptying thalf was not lower after administration of insulin, compared with saline. After 6 months of intensive therapy, levels of glycated hemoglobin decreased from 10.6%±0.3% to 9%±0.4% (P=.0003), but gastric emptying thalf did not change (92±8 min before, 92±7 min after). Gastric emptying did not correlate with plasma levels of GLP1 and amylin. Conclusions Two-thirds of patients with poorly-controlled type 2 diabetes have mostly asymptomatic yet abnormal gastric emptying. Higher fasting blood levels of glucose are associated with faster gastric emptying. Overnight and sustained (6 months) improvements in glycemic control do not affect gastric emptying. PMID:25041866

Local Membrane Deformations Activate Ca2+-Dependent K+ and Anionic Currents in Intact Human Red Blood Cells

PubMed Central

Dyrda, Agnieszka; Cytlak, Urszula; Ciuraszkiewicz, Anna; Lipinska, Agnieszka; Cueff, Anne; Bouyer, Guillaume; Egée, Stéphane; Bennekou, Poul; Lew, Virgilio L.; Thomas, Serge L. Y.

2010-01-01

Background The mechanical, rheological and shape properties of red blood cells are determined by their cortical cytoskeleton, evolutionarily optimized to provide the dynamic deformability required for flow through capillaries much narrower than the cell's diameter. The shear stress induced by such flow, as well as the local membrane deformations generated in certain pathological conditions, such as sickle cell anemia, have been shown to increase membrane permeability, based largely on experimentation with red cell suspensions. We attempted here the first measurements of membrane currents activated by a local and controlled membrane deformation in single red blood cells under on-cell patch clamp to define the nature of the stretch-activated currents. Methodology/Principal Findings The cell-attached configuration of the patch-clamp technique was used to allow recordings of single channel activity in intact red blood cells. Gigaohm seal formation was obtained with and without membrane deformation. Deformation was induced by the application of a negative pressure pulse of 10 mmHg for less than 5 s. Currents were only detected when the membrane was seen domed under negative pressure within the patch-pipette. K+ and Cl− currents were strictly dependent on the presence of Ca2+. The Ca2+-dependent currents were transient, with typical decay half-times of about 5–10 min, suggesting the spontaneous inactivation of a stretch-activated Ca2+ permeability (PCa). These results indicate that local membrane deformations can transiently activate a Ca2+ permeability pathway leading to increased [Ca2+]i, secondary activation of Ca2+-sensitive K+ channels (Gardos channel, IK1, KCa3.1), and hyperpolarization-induced anion currents. Conclusions/Significance The stretch-activated transient PCa observed here under local membrane deformation is a likely contributor to the Ca2+-mediated effects observed during the normal aging process of red blood cells, and to the increased Ca2+ content of red cells in certain hereditary anemias such as thalassemia and sickle cell anemia. PMID:20195477

Local membrane deformations activate Ca2+-dependent K+ and anionic currents in intact human red blood cells.

PubMed

Dyrda, Agnieszka; Cytlak, Urszula; Ciuraszkiewicz, Anna; Lipinska, Agnieszka; Cueff, Anne; Bouyer, Guillaume; Egée, Stéphane; Bennekou, Poul; Lew, Virgilio L; Thomas, Serge L Y

2010-02-26

The mechanical, rheological and shape properties of red blood cells are determined by their cortical cytoskeleton, evolutionarily optimized to provide the dynamic deformability required for flow through capillaries much narrower than the cell's diameter. The shear stress induced by such flow, as well as the local membrane deformations generated in certain pathological conditions, such as sickle cell anemia, have been shown to increase membrane permeability, based largely on experimentation with red cell suspensions. We attempted here the first measurements of membrane currents activated by a local and controlled membrane deformation in single red blood cells under on-cell patch clamp to define the nature of the stretch-activated currents. The cell-attached configuration of the patch-clamp technique was used to allow recordings of single channel activity in intact red blood cells. Gigaohm seal formation was obtained with and without membrane deformation. Deformation was induced by the application of a negative pressure pulse of 10 mmHg for less than 5 s. Currents were only detected when the membrane was seen domed under negative pressure within the patch-pipette. K(+) and Cl(-) currents were strictly dependent on the presence of Ca(2+). The Ca(2+)-dependent currents were transient, with typical decay half-times of about 5-10 min, suggesting the spontaneous inactivation of a stretch-activated Ca(2+) permeability (PCa). These results indicate that local membrane deformations can transiently activate a Ca(2+) permeability pathway leading to increased [Ca(2+)](i), secondary activation of Ca(2+)-sensitive K(+) channels (Gardos channel, IK1, KCa3.1), and hyperpolarization-induced anion currents. The stretch-activated transient PCa observed here under local membrane deformation is a likely contributor to the Ca(2+)-mediated effects observed during the normal aging process of red blood cells, and to the increased Ca(2+) content of red cells in certain hereditary anemias such as thalassemia and sickle cell anemia.

Effect of guar gum on gastric emptying in growing pigs.

PubMed

Rainbird, A L; Low, A G

1986-01-01

1. Simple gastric cannulas were surgically fitted to four pigs, initially of 30 kg live weight, to examine the effects of guar gum on gastric emptying. 2. Four semi-purified high-fat diets based on starch, casein, soya-bean oil and tallow were given to each pig. They contained 0 (control), 20, 40 or 60 g powdered guar gum/kg diet. The meals as fed contained 257 g dry matter (DM)/kg. 3. The contents of the stomach were evacuated, with rinsing, before feeding or 0.5, 1, 2 or 4 h after feeding. 4. The mean pH of the digesta was unaffected by guar gum until 4 h after feeding when the value increased as the amount of guar gum in the diet rose. 5. The only significant effects of guar gum on the emptying of digesta and its components (compared with the control diet) were to reduce the rate of emptying of (a) digesta 1 h after feeding (60 g/kg diet) and 4 h after feeding (40 and 60 g/kg diets), (b) dry matter and glucose 1 h after feeding (60 g/kg diet), (c) nitrogen 1 h after feeding (60 g/kg diet) and 4 h after feeding (40 and 60 g/kg diets). 6. When expressed on a half-time (T50) basis, the emptying of digesta and N (but not of DM and glucose) were significantly slower for diets containing 40 and 60 g guar gum/kg than for the control diet. 7. The apparent viscosity of the gastric digesta ranged between 0.5 and 23.7% of the values for the diets as consumed. 8. It was concluded that the effects of guar gum on gastric emptying of high-solid meals were small, and that this was unlikely to be an important aspect of the mechanism by which guar gum reduces postprandial blood glucose concentrations.

Secondary succession: Composition of the vegetation and primary production in the field-to-forest at Brookhaven, Long Island, N.Y.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodwell,G.M.; Holt, B. R.; Flaccus, E.

1973-08-23

Natural communities respond to disruption through a series of changes in plant and animal communities that are broadly predictable. The field-to-forest sere of central Long Island follows the pattern set forth earlier for the Piedmont of North Carolina and for New Jersey. The communities of herbs that occur in the years immediately after abandonment are followed by an Andropogon stage which is replaced before the 20th year by pine forest. The pine is replaced in the next 25 years by oak-pine, which in the normal Course is followed by oak-hickory. With repeated burning the oak-pine stage in various combinations ofmore » oaks and pine may be maintained indefinitely. Diversity, measured as number of species per unit land area, increased in this sere through the 3-5th years after abandonment to a maximum, dropped, and rose again in the later forest stages. Exotics were a conspicuous part of the communities of the earlier stages but their importance diminished as succession progressed and their contribution to net production was zero beyond the 20th year. The removal of exotics would probably not have changed the pattern of diversity appreciably. Net primary production increased with succession in this sere with major changes occurring as life-forms of the dominants shifted to woody plants. The peak net production was in the most mature forest, about 1200 g/m{sup 2}/yr. Root/shoot ratios declined from 4-5 in the early stages of succession to 0.3-0.5 with later stages. The standing crop of organic matter including humus throughout the sere was about 15 times the net production, indicating a halftime of residence for all organic matter throughout the sere of about 10 years.« less

Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones.

PubMed Central

Tamarappoo, B K; Verkman, A S

1998-01-01

Five single-point aquaporin-2 (AQP2) mutations that cause non-X-linked nephrogenic diabetes insipidus (NDI) were characterized to establish the cellular defect and to develop therapeutic strategies. In Xenopus oocytes expressing AQP2 cRNAs, single-channel water permeabilities of mutants L22V, T126M, and A147T were similar to that of wild-type AQP2, whereas R187C and C181W were nonfunctional. In [35S]methionine pulse-chase experiments in transiently transfected CHO cells, half-times for AQP2 degradation were approximately 4 h for wild-type AQP2 and L22V, and mildly decreased for T126M (2.7 h), C181W (2.4 h), R187C (2.0 h), and A147T (1.8 h). Immunofluorescence showed three distinct AQP2-staining patterns: plasma membrane and endosomal staining (wild-type, L22V), endoplasmic reticulum (ER) staining (T126M > A147T approximately R187C), or a mixed pattern of reticular and perinuclear vesicular staining. Immunoblot of fractionated vesicles confirmed primary ER localization of T126M, R187C, and A147T. To determine if the AQP2-trafficking defect is correctable, cells were incubated with the "chemical chaperone" glycerol for 48 h. Immunoblot showed that glycerol produced a nearly complete redistribution of AQP2 (T126M, A147T, and R187C) from ER to membrane/endosome fractions. Immunofluorescence confirmed the cellular redistribution. Redistribution of AQP2 mutants was also demonstrated in transfected MDCK cells, and using the chaperones TMAO and DMSO in place of glycerol in CHO cells. Water permeability measurements indicated that functional correction was achieved. These results indicate defective mammalian cell processing of mutant AQP2 water channels in NDI, and provide evidence for pharmacological correction of the processing defect by chemical chaperones. PMID:9593782

An estimate of the inventory of technetium-99 in the sub-tidal sediments of the Irish Sea.

PubMed

Jenkinson, Stuart B; McCubbin, David; Kennedy, Paul H W; Dewar, Alastair; Bonfield, Rachel; Leonard, Kinson S

2014-07-01

Published results from earlier studies have provided indications that measurable quantities of technetium-99 ((99)Tc) have accumulated in the sub-tidal sediments of the Irish Sea. This is due to the enhanced discharges from the Sellafield nuclear reprocessing plant in Cumbria, UK (between 1994 and 2004). Depth distributions of (99)Tc concentrations in sub-tidal sediments have been determined from a limited number of Irish Sea sites, following the collection of deep sediment cores (up to 2 m in depth), sampled in two research cruise surveys in 2005 and 2006. Vertical concentration profiles of (99)Tc from a range of substrates in the Irish Sea are presented here and these have been used to produce an estimate of the total inventory of (99)Tc residing in the sub-tidal sediments of the Irish Sea. Significant variation was observed between (99)Tc concentrations in the sediment samples, as well as in the shape of individual depth profiles. As anticipated, concentrations tended to be greater on fine-grained (muddy) substrates and showed a general decrease with distance from Sellafield. Vertical concentration profiles of (137)Cs, and (137)Cs data from published work, have also been considered to evaluate the use of the relatively few (99)Tc core data (upon which to determine the (99)Tc inventory). The inventories of (99)Tc and (137)Cs are estimated to have been of the order of 30 and 455 terabecquerels (TBq), respectively, or ∼2% of the total cumulative Sellafield discharge for each of the two radionuclides. The residence half-time of (137)Cs in the sub-tidal sediments of the Irish Sea is estimated to be in the order of ∼16 years. Therefore, as the Kd values for (99)Tc and (137)Cs are similar, this also provides an indicative value to predict future losses of (99)Tc from the sediment reservoir. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

The human alimentary tract transfer and body retention of environmental polonium-210.

PubMed

Hunt, G J; Rumney, H S

2007-12-01

This paper presents the results of a 4 year study to investigate the human alimentary tract transfer factor (f(A) value) and body retention of 210 Po in shellfish. In the first 3 years, mussels (Mytilus edulis L.), cockles (Cerastoderma edule L.) and brown meat from crab (Cancer pagurus L.) were successively studied. In each year five volunteers (from a pool of seven) ate a suitable portion of the shellfish and provided 24 h samples of excreta usually for 3 days before and for at least 7 days during and after eating. Subsamples of shellfish were analysed to determine the intakes of 210 Po. Faeces were analysed and the data used to assess apparent fA values. Urine samples were analysed in the mussel and crab studies to provide urinary excretion parameters. Pb-210 was also analysed during the mussel study; the levels were low, leading to large uncertainties, but confirming the negligible effect of radioactive decay to its granddaughter 210 Po in the main study. In the fourth year, larger samples of brown crab meat were eaten by five volunteers and faecal samples were taken at suitable times over periods of up to 43 days to study body retention of 210 Po. The first approximately 7 days provided additional data on fA values. Pooled results for the apparent fA for the whole study lay in the range 0.15-0.65 with a mean of 0.46; corrections for endogenous excretion suggest a true fA value of approximately 0.51, supporting the value of 0.5 currently used by the International Commission on Radiological Protection (ICRP). The retention data suggest a biological half-time of about 40 days, in broad consistency with the 50 days currently used by the ICRP. Thus there is no strong evidence from this study suggesting a change in dose coefficient for 210 Po. Full experimental data are provided to allow independent further interpretation.

In-vitro study of methylglyoxal and aspirin effects on fibrinolysis parameters.

PubMed

Pouya, Fahima D; Zavar-Reza, Javad; Jalali, Beman A

2013-10-01

Methylglyoxal is a reactive α, β dicarbonyl aldehyde compound that originates from various biochemical pathways. Some studies suggest that increased methylglyoxal in blood leads to changes in fibrinolysis; however, the precise mechanism is not clear. The aim of this study was to compare different concentrations of methylglyoxal and aspirin on fibrinolysis in the plasma of healthy individuals in vitro. Different concentrations of methylglyoxal (5, 50, 100, and 500 μmol/l) and aspirin (1, 10, and 100 mg/l) were added to the plasma citrate. They were incubated at 37°C for 24 h. Then, fibrinolysis parameters were analyzed by the turbidimetric procedure at 405 nm. The Independent Samples t-test was utilized to compare them (P < 0.05). Findings revealed that methylglyoxal at 500 μmol/l with aspirin 100 mg/l had significant changes in the maximum lysis velocity (0.163 ± 0.003), half-time lysis (240 ± 10.00), the total lysis time (485 ± 5.00), lag time in lysis (126 ± 5.77), compared with methylglyoxal at 500 μmol/l (0.104 ± 0.005), (276 ± 5.77), (570 ± 10.00), and (186 ± 5.77), respectively (P < 0.05). Methylglyoxal at 500 μmol/l with aspirin 1 mg/l did not significantly change in either parameter (P > 0.05). Methylglyoxal at 100 μmol/l with aspirin 1 mg/l did not significantly change in either fibrinolysis parameter (P > 0.05), compared with methylglyoxal at 100 μmol/l. Methylglyoxal at 5 μmol/l with aspirin (1, 10, 100  mg/l) changed in all fibrinolysis parameters (P < 0.05), compared with methylglyoxal at 5 μmol/l. The other concentrations were compared in the same way. Aspirin (more than 1 mg/l) had more effect on higher concentrations of methylglyoxal. It increased the velocity of lysis of the clot and shortened clot lysis.

Crystal Nucleation and Crystal Growth and Mass Transfer in Internally Mixed Sucrose/NaNO3 Particles.

PubMed

Ji, Zhi-Ru; Zhang, Yun; Pang, Shu-Feng; Zhang, Yun-Hong

2017-10-19

Secondary organic aerosols (SOA) can exist in a glassy or semisolid state under low relative humidity (RH) conditions, in which the particles show nonequilibrium kinetic characteristics with changing ambient RH. Here, we selected internally mixed sucrose/NaNO 3 droplets with organic to inorganic molar ratios (OIRs) of 1:8, 1:4, 1:2, and 1:1 as a proxy for multicomponent ambient aerosols to study crystal nucleation and growth processes and water transport under a highly viscous state with the combination of an RH-controlling system and a vacuum Fourier transform infrared (FTIR) spectrometer. The initial efflorescence RH (ERH) of NaNO 3 decreased from ∼45% for pure NaNO 3 droplets to ∼38.6 and ∼37.9% for the 1:8 and 1:4 sucrose/NaNO 3 droplets, respectively, while no crystallization of NaNO 3 occurred for the 1:2 and 1:1 droplets in the whole RH range. Thus, the addition of sucrose delayed the ERH and even completely inhibited nucleation of NaNO 3 in the mixed droplets. In addition, the crystal growth of NaNO 3 was suppressed in the 1:4 and 1:8 droplets most likely due to the slow diffusion of Na + and NO 3 - ions at low RH. Water uptake/release of sucrose/NaNO 3 particles quickly arrived at equilibrium at high RH, while the hygroscopic process was kinetically controlled under low RH. The half-time ratio between the liquid water content and the RH was used to describe the mass transfer behavior. For the 1:1 droplets, no mass limitation was observed with the ratio approaching to 1 when the RH was higher than 53%. The ratio increased 1 order of magnitude under an ultraviscous state with RH ranging from 53 to 15% and increased a further 1 order of magnitude at RH < 15% under a glassy state.

Metabolism and pharmacokinetics of the combination Zidovudine plus Lamivudine in the adult Erythrocebus patas monkey determined by liquid chromatography-tandem mass spectrometric analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Divi, Rao L.; Doerge, Daniel R.; Twaddle, Nathan C.

2008-01-15

Because of their similarity to humans, non-human primates constitute useful preclinical models in which to examine potential human drug toxicities. Antiretroviral nucleoside reverse transcriptase inhibitor (NRTI) toxicity is currently under investigation in Erythrocebus patas monkeys, and whereas NRTI pharmacokinetics have been studied in other monkey species, pharmacokinetics for Zidovudine plus Lamivudine (AZT/3TC) dosing have not been reported in the patas. Here we present 24 h serum pharmacokinetic parameters after a single oral exposure to the combination of AZT (40 mg) and 3TC (24 mg), doses equivalent to a human daily dose of Combivir (registered) . The patas (n = 3)more » AZT/3TC pharmacokinetic profiles were similar to those seen in other primate species. Average maximum serum concentrations (C{sub max}) for AZT and 3TC were 2.35 and 2.65 {mu}g/ml, respectively, and were observed at 0.83 h (T{sub max}). C{sub max} was 13.34 {mu}g/ml for the AZT-glucuronide (AZT-G) and was 0.023 {mu}g/ml for the potentially toxic minor metabolite 3'-amino-3'-deoxythymidine (AMT), both occurring at about 1 h after dosing. Similar elimination half-times, 0.70 and 0.68 h{sup -1}, were found for AZT and AZT-G, respectively, while 3TC was eliminated about half as fast (0.33 h{sup -1}) resulting in AUC{sub (0-{infinity})} values of 6.97 {mu}g/ml h for 3TC, 2.99 {mu}g/ml h for AZT, 20.5 {mu}g/ml h for AZT-G and 0.002 for AMT 6.97 {mu}g/ml h. This study shows similar metabolism and pharmacokinetics for oral administration of AZT/3TC in the adult patas monkey, other primate species and humans. The data validate the use of the patas monkey for studies of NRTI toxicity.« less

Mitochondrial Ca2+ homeostasis during Ca2+ influx and Ca2+ release in gastric myocytes from Bufo marinus

PubMed Central

Drummond, Robert M; Mix, T Christian H; Tuft, Richard A; Walsh, John V; Fay, Fredric S

2000-01-01

The Ca2+-sensitive fluorescent indicator rhod-2 was used to monitor mitochondrial Ca2+ concentration ([Ca2+]m) in gastric smooth muscle cells from Bufo marinus. In some studies, fura-2 was used in combination with rhod-2, allowing simultaneous measurement of cytoplasmic Ca2+ concentration ([Ca2+]i) and [Ca2+]m, respectively. During a short train of depolarizations, which causes Ca2+ influx from the extracellular medium, there was an increase in both [Ca2+]i and [Ca2+]m. The half-time (t½) to peak for the increase in [Ca2+]m was considerably longer than the t½ to peak for the increase in [Ca2+]i. [Ca2+]m remained elevated for tens of seconds after [Ca2+]i had returned to its resting value. Stimulation with caffeine, which causes release of Ca2+ from the sarcoplasmic reticulum (SR), also produced increases in both [Ca2+]i and [Ca2+]m. The values of t½ to peak for the increase in [Ca2+] in both cytoplasm and mitochondria were similar; however, [Ca2+]i returned to baseline values much faster than [Ca2+]m. Using a wide-field digital imaging microscope, changes in [Ca2+]m were monitored within individual mitochondria in situ, during stimulation of Ca2+ influx or Ca2+ release from the SR. Mitochondrial Ca2+ uptake during depolarizing stimulation caused depolarization of the mitochondrial membrane potential. The mitochondrial membrane potential recovered considerably faster than the recovery of [Ca2+]m. This study shows that Ca2+ influx from the extracellular medium and Ca2+ release from the SR are capable of increasing [Ca2+]m in smooth muscle cells. The efflux of Ca2+ from the mitochondria is a slow process and appears to be dependent upon the amount of Ca2+ in the SR. PMID:10713963

Caffeine supplementation does not affect match activities and fatigue resistance during match play in young football players.

PubMed

Pettersen, Svein Arne; Krustrup, Peter; Bendiksen, Mads; Randers, Morten Bredsgaard; Brito, Joao; Bangsbo, Jens; Jin, Yun; Mohr, Magni

2014-12-01

Abstract The study examined the effect of caffeine supplementation on match activities and development of fatigue during a football match. In a randomised, double-blind cross-over design, two experimental football games separated by 7 days were organised between the junior teams of two professional football clubs (17.6 ± 1.1 years (±s), 71.7 ± 6.9 kg, 13.9% ± 5.0% body fat). The players ingested either a capsule of 6 mg · kg -1  b.w. caffeine or placebo (dextrose) 65 min prior to the matches. Match activities were assessed using the ZXY match analysis system, and a Yo-Yo intermittent recovery test-level 2 (Yo-Yo IR2) was conducted immediately post-game. Heart rate was monitored throughout the game, and blood samples were obtained at baseline, half-time and after the game. There were no differences between caffeine and placebo regarding total distance covered (10,062 ± 916 vs 9854 ± 901 m), high-intensity running (557 ± 178 vs 642 ± 240 m), sprinting distance (109 ± 58 vs 112 ± 69 m) or acceleration counts (123 ± 31 vs 126 ± 24). In both trials, players displayed lower (P < 0.05) values in total distance and acceleration counts in the last 15 min compared to all other 15-min periods of the matches. Post-game Yo-Yo IR2 performance was not different between game trials (caffeine: 829 ± 322 m; placebo 819 ± 289 m). In conclusion, oral caffeine administration does not appear to have an ergogenic effect in young football players during match play.

Mitral valve resistance determines hemodynamic consequences of severe rheumatic mitral stenosis and immediate outcomes of percutaneous valvuloplasty.

PubMed

Sanati, Hamidreza; Zolfaghari, Reza; Samiei, Niloufar; Rezaei, Yousef; Chitsazan, Mitra; Zahedmehr, Ali; Shakerian, Farshad; Kiani, Reza; Firouzi, Ata; Rezaei Tabrizi, Reza

2017-02-01

The mitral valve area (MVA) poorly reflects the hemodynamic status of (MS). In this study, we compared the MVA with mitral valve resistance (MVR) with regard to the determination of hemodynamic consequences of MS and the immediate outcomes of percutaneous balloon mitral valvuloplasty (PBMV). In a prospective study, 36 patients with severe rheumatic MS with left ventricular ejection fraction (LVEF) >50% were evaluated. They underwent transthoracic echocardiography (TTE) and catheterization. The MVA was measured by two-dimensional planimetry and pressure half-time (PHT), and the MVR was calculated using the equation: 1333 × transmitral pressure gradient mean transmitral diastolic flow rate. The patients' mean age was 47.8±10.5 years. MVR ≥140.6 dynes·s/cm 5 detected systolic pulmonary arterial pressure (sPAP) >55 mm Hg with a sensitivity of 100% and a specificity of 74%. The sensitivity and specificity of MVA<0.75 cm 2 to discriminate elevated sPAP were 81% and 89%, respectively. PHT ≥323.5 mseconds had a sensitivity of 78% and a specificity of 96% to detect an elevated sPAP. To predict a successful PBMV, preprocedural MVR ≥106.1 dynes·s/cm 5 had a sensitivity of 100% and a specificity of 67% (area under the curve [AUC]=0.763; 95% confidence interval [CI]=0.520-1.006; P=.034); preprocedural MVA <0.95 cm 2 had a sensitivity of 78% and a specificity of 73% (AUC=0.730; 95% CI=0.503-0.956; P=.065); and preprocedural PHT ≥210.5 mseconds had a sensitivity of 73% and a specificity of 78% (AUC=0.707; 95% CI=0.474-0.941; P=.095). MVR seems to be more accurate than MVA in determining the hemodynamic consequences of severe MS as determined by sPAP. In addition, preprocedural MVR detected successful PBMVs. © 2017, Wiley Periodicals, Inc.

Development and validation of a large, modular test meal with liquid and solid components for assessment of gastric motor and sensory function by non-invasive imaging.

PubMed

Parker, H L; Tucker, E; Hoad, C L; Pal, A; Costigan, C; Hudders, N; Perkins, A; Blackshaw, E; Gowland, P; Marciani, L; Fox, M R

2016-04-01

Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study introduces the large 'Nottingham Test Meal' (NTM) for assessment of gastric motor and sensory function by non-invasive imaging. NTM comprises 400 mL liquid nutrient (0.75 kcal/mL) and 12 solid agar-beads (0 kcal) with known breaking strength. Gastric fullness and dyspeptic sensations were documented by 100 mm visual analogue scale (VAS). Gastric emptying (GE) were measured in 24 healthy volunteers (HVs) by gastric scintigraphy (GS) and magnetic resonance imaging (MRI). The contribution of secretion to gastric volume was assessed. Parameters that describe GE were calculated from validated models. Inter-observer agreement and reproducibility were assessed. NTM produced moderate fullness (VAS ≥30) but no more than mild dyspeptic symptoms (VAS <30) in 24 HVs. Stable binding of meal components to labels in gastric conditions was confirmed. Distinct early and late-phase GE were detected by both modalities. Liquid GE half-time was median 49 (95% CI: 36-62) min and 68 (57-71) min for GS and MRI, respectively. Differences between GS and MRI measurements were explained by the contribution of gastric secretion. Breaking strength for agar-beads was 0.8 N/m(2) such that median 25 (8-50) % intact agar-beads and 65 (47-74) % solid material remained at 120 min on MRI and GS, respectively. Good reproducibility for liquid GE parameters was present and GE was not altered by agar-beads. The NTM provided an objective assessment of gastric motor and sensory function. The results were reproducible and liquid emptying was not affected by non-nutrient agar-beads. The method is potentially suitable for clinical practice. © 2016 John Wiley & Sons Ltd.

Mechanism-based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers.

PubMed

Yassen, A; Olofsen, E; Romberg, R; Sarton, E; Teppema, L; Danhof, M; Dahan, A

2007-01-01

The objective of this study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of buprenorphine and fentanyl for the respiratory depressant effect in healthy volunteers. Data on the time course of the ventilatory response at a fixed P(ET)CO(2) of 50 mm Hg and P(ET)O(2) of 110 mm Hg following intravenous administration of buprenorphine and fentanyl were obtained from two phase I studies (50 volunteers received buprenorphine: 0.05-0.6 mg/70 kg and 24 volunteers received fentanyl: 0.075-0.5 mg/70 kg). The PK/PD correlations were analyzed using nonlinear mixed effects modeling. A two- and three-compartment pharmacokinetic model characterized the time course of fentanyl and buprenorphine concentration, respectively. Three structurally different PK/PD models were evaluated for their appropriateness to describe the time course of respiratory depression: (1) a biophase distribution model with a fractional sigmoid E(max) pharmacodynamic model, (2) a receptor association/dissociation model with a linear transduction function, and (3) a combined biophase distribution-receptor association/dissociation model with a linear transduction function. The results show that for fentanyl hysteresis is entirely determined by the biophase distribution kinetics, whereas for buprenorphine hysteresis is caused by a combination of biophase distribution kinetics and receptor association/dissociation kinetics. The half-time values of biophase equilibration (t(1/2, k(eo))) were 16.4 and 75.3 min for fentanyl and buprenorphine, respectively. In addition, for buprenorphine, the value of k(on) was 0.246 ml/ng/min and the value of k(off) was 0.0102 min(-1). The concentration-effect relationship of buprenorphine was characterized by a ceiling effect at higher concentrations (intrinsic activity alpha=0.56, 95% confidence interval (CI): 0.50-0.62), whereas fentanyl displayed full respiratory depressant effect (alpha=0.91, 95% CI: 0.19-1.62).

Photobiological hydrogen production and carbon dioxide sequestration

NASA Astrophysics Data System (ADS)

Berberoglu, Halil

Photobiological hydrogen production is an alternative to thermochemical and electrolytic technologies with the advantage of carbon dioxide sequestration. However, it suffers from low solar to hydrogen energy conversion efficiency due to limited light transfer, mass transfer, and nutrient medium composition. The present study aims at addressing these limitations and can be divided in three parts: (1) experimental measurements of the radiation characteristics of hydrogen producing and carbon dioxide consuming microorganisms, (2) solar radiation transfer modeling and simulation in photobioreactors, and (3) parametric experiments of photobiological hydrogen production and carbon dioxide sequestration. First, solar radiation transfer in photobioreactors containing microorganisms and bubbles was modeled using the radiative transport equation (RTE) and solved using the modified method of characteristics. The study concluded that Beer-Lambert's law gives inaccurate results and anisotropic scattering must be accounted for to predict the local irradiance inside a photobioreactor. The need for accurate measurement of the complete set of radiation characteristics of microorganisms was established. Then, experimental setup and analysis methods for measuring the complete set of radiation characteristics of microorganisms have been developed and successfully validated experimentally. A database of the radiation characteristics of representative microorganisms have been created including the cyanobacteria Anabaena variabilis, the purple non-sulfur bacteria Rhodobacter sphaeroides and the green algae Chlamydomonas reinhardtii along with its three genetically engineered strains. This enabled, for the first time, quantitative assessment of the effect of genetic engineering on the radiation characteristics of microorganisms. In addition, a parametric experimental study has been performed to model the growth, CO2 consumption, and H 2 production of Anabaena variabilis as functions of irradiance and CO2 concentration. Kinetic models were successfully developed based on the Monod model and on a novel scaling analysis employing the CO2 consumption half-time as the time scale. Finally, the growth and hydrogen production of Anabaena variabilis have been compared in a flat panel photobioreactor using three different nutrient media under otherwise similar conditions. Light to hydrogen energy conversion efficiency for Allen-Arnon medium was superior by a factor of 5.5 to both BG-11 and BG-11o media. This was attributed to the presence of vanadium and larger heterocyst frequency observed in the Allen-Arnon medium.

In vitro dissolution of strontium titanate to estimate clearance rates in human lungs

NASA Astrophysics Data System (ADS)

Anderson, Jeri Lynn

At the In-Tank Precipitation facility (ITP) of the Savannah River Site, strontium and other radionuclides are removed from high-level radioactive waste and sent to the Defense Waste Processing Facility (DWPF). Strontium removal is accomplished by ion-exchange using monosodium titanate slurry which creates a form of strontium titanate with unknown solubility characteristics. In the case of accidental inhalation of a compound containing radioactive strontium, the ICRP, in Publication 66, recommends using default values for rates of absorption into body fluids at the lungs in the absence of reliable human or animal data. The default value depends on whether the absorption is considered to be fast, moderate, or slow (Type F, M, or S). Current dose assessment for an individual upon inadvertent exposure to airborne radioactive strontium assumes that all strontium compounds are Type F (soluble) or Type S (insoluble). Pure high-fired strontium titanate (SrTiOsb3) is considered Type S. The purpose of this project was to determine the solubility of strontium titanate in the form created at the ITP facility. An in vitro dissolution study was done with a precipitate simulant and with several types of strontium titanate and the results were compared. An in vivo study was also performed with high-fired SrTiOsb3 in rats. The data from both studies were used independently to assign the compounds to absorption type based on criteria specified in ICRP 71. Results of the in vitro studies showed that the DWPF simulant should be assigned to Type M and the strontium titanate should be assigned to Type S. It is possible the difference in the DWPF simulant is due to the other chemicals present. Results of the in vivo study verified that SrTiOsb3 should be assigned to Type S. Lung clearance data of SrTiOsb3 from rats showed that 85% cleared within the first 24 hours and the remaining 15% with a half-time of 130 days. The initial rapid clearance is attributed to deposition in airways as compared to the alveolar region.

Absorption and retention of nickel from drinking water in relation to food intake and nickel sensitivity.

PubMed

Nielsen, G D; Søderberg, U; Jørgensen, P J; Templeton, D M; Rasmussen, S N; Andersen, K E; Grandjean, P

1999-01-01

Two studies were performed to examine the influence of fasting and food intake on the absorption and retention of nickel added to drinking water and to determine if nickel sensitization played any role in this regard. First, eight nonallergic male volunteers fasted overnight before being given nickel in drinking water (12 micrograms Ni/kg) and, at different time intervals, standardized 1400-kJ portions of scrambled eggs. When nickel was ingested in water 30 min or 1 h prior to the meal, peak nickel concentrations in serum occurred 1 h after the water intake, and the peak was 13-fold higher than the one seen 1 h after simultaneous intake of nickel-containing water and scrambled eggs. In the latter case, a smaller, delayed peak occurred 3 h after the meal. Median urinary nickel excretion half-times varied between 19.9 and 26.7 h. Within 3 days, the amount of nickel excreted corresponded to 2.5% of the nickel ingested when it was mixed into the scrambled eggs. Increasing amounts were excreted as the interval between the water and the meal increased, with 25.8% of the administered dose being excreted when the eggs were served 4 h prior to the nickel-containing drinking water. In the second experiment, a stable nickel isotope, 61Ni, was given in drinking water to 20 nickel-sensitized women and 20 age-matched controls, both groups having vesicular hand eczema of the pompholyx type. Nine of 20 nickel allergic eczema patients experienced aggravation of hand eczema after nickel administration, and three also developed a maculopapular exanthema. No exacerbation was seen in the control group. The course of nickel absorption and excretion in the allergic groups did not differ and was similar to the pattern seen in the first study, although the absorption in the women was less. A sex-related difference in gastric emptying rates may play a role. Thus, food intake and gastric emptying are of substantial significance for the bioavailability of nickel from aqueous solutions. Copyright 1999 Academic Press.

Clinical evaluation of reducing acquisition time on single-photon emission computed tomography image quality using proprietary resolution recovery software.

PubMed

Aldridge, Matthew D; Waddington, Wendy W; Dickson, John C; Prakash, Vineet; Ell, Peter J; Bomanji, Jamshed B

2013-11-01

A three-dimensional model-based resolution recovery (RR) reconstruction algorithm that compensates for collimator-detector response, resulting in an improvement in reconstructed spatial resolution and signal-to-noise ratio of single-photon emission computed tomography (SPECT) images, was tested. The software is said to retain image quality even with reduced acquisition time. Clinically, any improvement in patient throughput without loss of quality is to be welcomed. Furthermore, future restrictions in radiotracer supplies may add value to this type of data analysis. The aims of this study were to assess improvement in image quality using the software and to evaluate the potential of performing reduced time acquisitions for bone and parathyroid SPECT applications. Data acquisition was performed using the local standard SPECT/CT protocols for 99mTc-hydroxymethylene diphosphonate bone and 99mTc-methoxyisobutylisonitrile parathyroid SPECT imaging. The principal modification applied was the acquisition of an eight-frame gated data set acquired using an ECG simulator with a fixed signal as the trigger. This had the effect of partitioning the data such that the effect of reduced time acquisitions could be assessed without conferring additional scanning time on the patient. The set of summed data sets was then independently reconstructed using the RR software to permit a blinded assessment of the effect of acquired counts upon reconstructed image quality as adjudged by three experienced observers. Data sets reconstructed with the RR software were compared with the local standard processing protocols; filtered back-projection and ordered-subset expectation-maximization. Thirty SPECT studies were assessed (20 bone and 10 parathyroid). The images reconstructed with the RR algorithm showed improved image quality for both full-time and half-time acquisitions over local current processing protocols (P<0.05). The RR algorithm improved image quality compared with local processing protocols and has been introduced into routine clinical use. SPECT acquisitions are now acquired at half of the time previously required. The method of binning the data can be applied to any other camera system to evaluate the reduction in acquisition time for similar processes. The potential for dose reduction is also inherent with this approach.

Epidemiology, co-morbidity, and impact on health-related quality of life of self-reported headache and musculoskeletal pain--a gender perspective.

PubMed

Bingefors, Kerstin; Isacson, Dag

2004-10-01

Headache and musculo-skeletal pain are major public health problems. Substantial proportions of the general population report that they experience pain problems that affect their work, daily living and social life. Epidemiological studies have consistently shown that the prevalence of most pain conditions is higher in women than in men. Cross-sectional survey in the county of Uppland, Sweden, 1995. Five thousand four hundred and four completed the questionnaire (response rate=68%). In these analyses for persons aged 20-64 years 4506 were included. Back pain (22.7%) and shoulder pain (21.0%) were the most commonly reported medical problems in the population with pain in arms/legs (15.7%) in fifth and headache (12.5%) in eight place. Major gender differences were found. The prevalence of pain conditions, especially headache, was higher among women. Women reported more severe pain. Co-morbidity between pain conditions and psychiatric and somatic problems was higher among women. Health-related quality of life (SF-36) differed by gender and type of pain condition. The physical dimensions of HRQoL were more affected by headache among men; psychological dimensions were more affected among women. Among both men and women, pain conditions were associated with poorer socioeconomic conditions and life-style factors but there were gender differences. Education and unemployment were important only among men while economical difficulties, half-time work and being married were associated with pain among women. Obesity, early disability retirement, long time sick-leave and lack of exercise were associated with pain conditions generally. Factors associated with pain conditions were unevenly distributed between genders. There are major differences between men and women in the prevalence and severity of self-reported pain in the population. Biological factors may explain some of the differences but the main explanation is presumably gender disparities in work, economy, daily living, social life and expectations between women and men. Although improved working conditions are of importance, deeper societal changes are needed to reduce the inequities in pain experiences between women and men.

SU-F-T-681: Does the Biophysical Modeling for Immunological Aspects in Radiotherapy Precisely Predict Tumor and Normal Tissue Responses?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oita, M; Nakata, K; Sasaki, M

2016-06-15

Purpose: Recent advances in immunotherapy make possible to combine with radiotherapy. The aim of this study was to assess the TCP/NTCP model with immunological aspects including stochastic distribution as intercellular uncertainties. Methods: In the clinical treatment planning system (Eclipse ver.11.0, Varian medical systems, US), biological parameters such as α/β, D50, γ, n, m, TD50 including repair parameters (bi-exponential repair) can be set as any given values to calculate the TCP/NTCP. Using a prostate cancer patient data with VMAT commissioned as a 6-MV photon beam of Novalis-Tx (BrainLab, US) in clinical use, the fraction schedule were hypothesized as 70–78Gy/35–39fr, 72–81Gy/40–45fr, 52.5–66Gy/16–22fr,more » 35–40Gy/5fr of 5–7 fractions in a week. By use of stochastic biological model applying for Gaussian distribution, the effects of the TCP/NTCP variation of repair parameters of the immune system as well as the intercellular uncertainty of tumor and normal tissues have been evaluated. Results: As respect to the difference of the α/β, the changes of the TCP/NTCP were increased in hypo-fraction regimens. The difference between the values of n and m affect the variation of the NTCP with the fraction schedules, independently. The elongation of repair half-time (long) increased the TCP/NTCP twice or much higher in the case of hypo-fraction scheme. For tumor, the repopulation parameters such as Tpot and Tstart, which is immunologically working to the tumor, improved TCP. Conclusion: Compared to default fixed value, which has affected by the probability of cell death and cure, hypo-fractionation schemes seemed to have advantages for the variations of the values of m. The possibility of an increase of the α/β or TD50 and repair parameters in tumor and normal tissue by immunological aspects were highly expected. For more precise prediction, treatment planning systems should be incorporated the complicated biological optimization in clinical practice combined with basic experiments data.« less

Spatially resolved assessment of hepatic function using 99mTc-IDA SPECT

PubMed Central

Wang, Hesheng; Cao, Yue

2013-01-01

Purpose: 99mTc-iminodiacetic acid (IDA) hepatobiliary imaging is usually quantified for hepatic function on the entire liver or regions of interest (ROIs) in the liver. The authors presented a method to estimate the hepatic extraction fraction (HEF) voxel-by-voxel from single-photon emission computed tomography (SPECT)/CT with a 99mTc-labeled IDA agent of mebrofenin and evaluated the spatially resolved HEF measurements with an independent physiological measurement. Methods: Fourteen patients with intrahepatic cancers were treated with radiation therapy (RT) and imaged by 99mTc-mebrofenin SPECT before and 1 month after RT. The dynamic SPECT volumes were with a resolution of 3.9 × 3.9 × 2.5 mm3. Throughout the whole liver with approximate 50 000 voxels, voxelwise HEF quantifications were estimated and compared between using arterial input function (AIF) from the heart and using vascular input function (VIF) from the spleen. The correlation between mean of the HEFs over the nontumor liver tissue and the overall liver function measured by Indocyanine green clearance half-time (T1/2) was assessed. Variation of the voxelwise estimation was evaluated in ROIs drawn in relatively homogeneous regions of the livers. The authors also examined effects of the time range parameter on the voxelwise HEF quantification. Results: Mean of the HEFs over the liver estimated using AIF significantly correlated with the physiological measurement T1/2 (r = 0.52, p = 0.0004), and the correlation was greatly improved by using VIF (r = 0.79, p < 0.0001). The parameter of time range for the retention phase did not lead to a significant difference in the means of the HEFs in the ROIs. Using VIF and a retention phase time range of 7–30 min, the relative variation of the voxelwise HEF in the ROIs was 10% ± 6% of respective mean HEF. Conclusions: The voxelwise HEF derived from 99mTc-IDA SPECT by the deconvolution analysis is feasible to assess the spatial distribution of hepatic function in the liver. PMID:24007177

Modelling the external radiation exposure from the Chernobyl fallout using data from the Swedish municipality measurement system.

PubMed

Jönsson, Mattias; Tondel, Martin; Isaksson, Mats; Finck, Robert; Wålinder, Robert; Mamour, Afrah; Rääf, Christopher

2017-11-01

In connection with the Chernobyl fallout and the subsequent deposition of radionuclides in Sweden, Swedish municipalities launched a measurement program to monitor the external radiation exposure. This program encompasses measurements of the ambient dose equivalent rate 1 m above ground at selected locations, and repeats those measurements at the same locations at 7-month intervals. Measurement data compiled from the seven locations with the highest deposition were combined with data from aerial surveys since May 1986 of ground deposition of 137 Cs, high-resolution gamma spectrometry performed at four locations in May 1986, and measurements from fixed continuous air gamma rate monitoring stations from 28 April to 15 May 1986. Based on these datasets, a model of the time pattern of the external dose rate in terms of ambient dose equivalent rate from the Chernobyl fallout was developed. The decrease in the ambient dose equivalent rate could, on average, be described by a four-component exponential decay function with effective half-times of 6.8 ± 0.3 d, 104 ± 26 d, 1.0 ± 0.02 y and 5.5 ± 0.09 y, respectively. The predominant contributions to the external dose rate in the first month were from short-lived fission products superseded by 134 Cs and then 137 Cs. Integrated over 70 y and using extrapolation of the curve fits, our model predicts that 137 Cs contributes about 60% and 134 Cs contributes about 30% of the external effective dose at these seven locations. The projected time-integrated 70 y external effective dose to an unshielded person from all nuclides per unit total activity deposition of 137 Cs is estimated to be 0.29 ± 0.0.08 mSv/(kBq m -2 ). These results are in agreement with those found in Chernobyl contaminated Russian forest areas, and emphasize the usefulness of maintaining a long-term and regular measurement program in contaminated areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of a miniature GM counter and a whole body counter in the study of potassium transport by the colon of normal, sodium-depleted and adrenalectomized rats in vivo

PubMed Central

Barnaby, C. F.; Edmonds, C. J.

1969-01-01

1. A method is described employing a whole-body counter and a miniature GM counter placed within the lumen of the gut which can be used to study the absorption rates and kinetics of labelled substances in the mucosal epithelium in vivo. The method was applied to the study of K transport by the mucosa of the descending colon of normal, Na-depleted and adrenalectomized rats. 2. The K influx rate was linearly related to luminal [K] over the range 5-80 mM. NaCN in the lumen produced a fall of electrical potential difference (p.d.) and of K secretion rate but did not reduce K influx rate. The findings were consistent with passive K influx. 3. The mucosal 42K content reached a steady value after 60-90 min of exposure to 42K in the lumen. The value was similar in normal and adrenalectomized rats but was greater in Na-depleted rats. 4. After replacement of luminal solution by a non-radioactive solution the fall of mucosal 42K content could be described, in the majority, by a curve having two exponential components with half-times of 8-10 and 65-106 min. Approximately half of the 42K outflow passed to the lumen. The rate constants were similar in all groups of rats. 5. The results analysed on the basis of representing the mucosal K as in two compartments, indicated that the observed absorption rate could not be accounted for by transport through these compartments alone and that most of the 42K crossed the mucosa by a fast pathway not detectable by the miniature GM counter. Most of the mucosal K was relatively inaccessible from the lumen. 6. Na depletion raised the transmucosal p.d., increased the K secretion rate and appeared to increase K permeability of the mucosa but the kinetics were unaltered. Accumulation of 42K in the mucosa was greater, suggesting that the permeability of the luminal face had increased. Adrenalectomy produced only one change, namely a reduction of K secretion rate. PMID:5361293

The effects of an increased calorie breakfast consumed prior to simulated match-play in Academy soccer players.

PubMed

Briggs, Marc A; Harper, Liam D; McNamee, Ged; Cockburn, Emma; Rumbold, Penny L S; Stevenson, Emma J; Russell, Mark

2017-08-01

Dietary analysis of Academy soccer players highlights that total energy and carbohydrate intakes are less than optimal, especially, on match-days. As UK Academy matches predominantly kick-off at ∼11:00 h, breakfast is likely the last pre-exercise meal and thus may provide an intervention opportunity on match-day. Accordingly, the physiological and performance effects of an increased calorie breakfast consumed ∼135-min before soccer-specific exercise was investigated. English Premier League Academy soccer players (n = 7) repeated a 90-min soccer match simulation on two occasions after consumption of habitual (B hab ; ∼1100 kJ) or increased (B inc ; ∼2100 kJ) energy breakfasts standardised for macronutrient contributions (∼60% carbohydrates, ∼15% proteins and ∼25% fats). Countermovement jump height, sprint velocities (15-m and 30-m), 30-m repeated sprint maintenance, gut fullness, abdominal discomfort and soccer dribbling performances were measured. Blood samples were taken at rest, pre-exercise, half-time and every 15-min during exercise. Although dribbling precision (P = .522; 29.9 ± 5.5 cm) and success (P = .505; 94 ± 8%) were unchanged throughout all time-points, mean dribbling speed was faster (4.3 ± 5.7%) in B inc relative to B hab (P = .023; 2.84 vs 2.75 m s -1 ). Greater feelings of gut fullness (67 ± 17%, P = .001) were observed in B inc without changes in abdominal discomfort (P = .595). All other physical performance measures and blood lactate and glucose concentrations were comparable between trials (all P > .05). Findings demonstrate that Academy soccer players were able to increase pre-match energy intake without experiencing abdominal discomfort; thus, likely contributing to the amelioration of energy deficits on match-days. Furthermore, whilst B inc produced limited benefits to physical performance, increased dribbling speed was identified, which may be of benefit to match-play.