Sample records for normalized release values

  1. PHAGE FORMATION IN STAPHYLOCOCCUS MUSCAE CULTURES

    PubMed Central

    Price, Winston H.

    1949-01-01

    1. The total nucleic acid synthesized by normal and by infected S. muscae suspensions is approximately the same. This is true for either lag phase cells or log phase cells. 2. The amount of nucleic acid synthesized per cell in normal cultures increases during the lag period and remains fairly constant during log growth. 3. The amount of nucleic acid synthesized per cell by infected cells increases during the whole course of the infection. 4. Infected cells synthesize less RNA and more DNA than normal cells. The ratio of RNA/DNA is larger in lag phase cells than in log phase cells. 5. Normal cells release neither ribonucleic acid nor desoxyribonucleic acid into the medium. 6. Infected cells release both ribonucleic acid and desoxyribonucleic acid into the medium. The time and extent of release depend upon the physiological state of the cells. 7. Infected lag phase cells may or may not show an increased RNA content. They release RNA, but not DNA, into the medium well before observable cellular lysis and before any virus is liberated. At virus liberation, the cell RNA content falls to a value below that initially present, while DNA, which increased during infection falls to approximately the original value. 8. Infected log cells show a continuous loss of cell RNA and a loss of DNA a short time after infection. At the time of virus liberation the cell RNA value is well below that initially present and the cells begin to lyse. PMID:18139006

  2. Effect of dietary macronutrients on postprandial incretin hormone release and satiety in obese and normal-weight women.

    PubMed

    Wikarek, Tomasz; Chudek, Jerzy; Owczarek, Aleksander; Olszanecka-Glinianowicz, Magdalena

    2014-01-28

    The aim of the present study was to assess the effect of dietary macronutrients on postprandial incretin responses and satiety and hunger sensation in obese and normal-weight women. A total of eleven obese and nine normal-weight women were recruited for the assessment of plasma concentrations of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and insulin and the sensation of satiety and hunger using a visual analogue scale before and during a 6 h period after administration of three different macronutrient test meals. The AUCtotal GLP-1 and AUCtotal GIP values were decreased in obese women after the consumption of a fatty meal and all the test meals, respectively. However, the AUCtotal insulin value after a carbohydrate meal was greater in the obese group. The AUCtotal satiety value was decreased only after the intake of the protein meal in obese women when compared with normal-weight women. After the consumption of the fatty meal, a significant positive correlation between maximum satiety sensation and the AUCtotal GLP-1 value in the obese group and that between minimum hunger sensation and the AUCtotal GLP-1 value in the normal-weight group were observed. In conclusion, the findings of the present study suggest that: (1) satiety sensation after consumption of carbohydrate and protein meals in the obese group is related to the postprandial insulin response, while after consumption of a fatty meal, it is related to the postprandial GLP-1 release; (2) the postprandial GIP response does not influence the sensation of satiety and hunger; (3) the reduced GLP-1 release after the intake of a fatty meal in obese individuals may explain impaired satiety sensation; (4) the impaired postprandial GIP response is not related to the consumption of macronutrients and may be the early indicator of incretin axis dysfunction in obese women.

  3. Human prolactin - 24-hour pattern with increased release during sleep.

    NASA Technical Reports Server (NTRS)

    Sassin, J. F.; Weitzman, E. D.; Kapen, S.; Frantz, A. G.

    1972-01-01

    Human prolactin was measured in plasma by radioimmunoassay at 20-minute intervals for a 24-hour period in each of six normal adults, whose sleep-wake cycles were monitored polygraphically. A marked diurnal variation in plasma concentrations was demonstrated, with highest values during sleep. Periods of episodic release occurred throughout the 24 hours.

  4. Impact of heat release on strain rate field in turbulent premixed Bunsen flames

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

    Coriton, Bruno Rene Leon; Frank, Jonathan H.

    2016-08-10

    The effects of combustion on the strain rate field are investigated in turbulent premixed CH 4/air Bunsen flames using simultaneous tomographic PIV and OH LIF measurements. Tomographic PIV provides three-dimensional velocity measurements, from which the complete strain rate tensor is determined. The OH LIF measurements are used to determine the position of the flame surface and the flame-normal orientation within the imaging plane. This combination of diagnostic techniques enables quantification of divergence as well as flame-normal and tangential strain rates, which are otherwise biased using only planar measurements. Measurements are compared in three lean-to-stoichiometric flames that have different amounts ofmore » heat release and Damköhler numbers greater than unity. The effects of heat release on the principal strain rates and their alignment relative to the local flame normal are analyzed. The extensive strain rate preferentially aligns with the flame normal in the reaction zone, which has been indicated by previous studies. The strength of this alignment increases with increasing heat release and, as a result, the flame-normal strain rate becomes highly extensive. These effects are associated with the gas expansion normal to the flame surface, which is largest for the stoichiometric flame. In the preheat zone, the compressive strain rate has a tendency to align with the flame normal. Away from the flame front, the flame – strain rate alignment is arbitrary in both the reactants and products. The flame-tangential strain rate is on average positive across the flame front, and therefore the turbulent strain rate field contributes to the enhancement of scalar gradients as in passive scalar turbulence. As a result, increases in heat release result in larger positive values of the divergence as well as flame-normal and tangential strain rates, the tangential strain rate has a weaker dependence on heat release than the flame-normal strain rate and the divergence.« less

  5. Radioimmunoassay of Human Serum Thyrotrophin

    PubMed Central

    Hall, Reginald; Amos, Jacqueline; Ormston, Brian J.

    1971-01-01

    The double antibody radioimmunoassay of serum thyroid-stimulating hormone (TSH) allows measurement of circulating levels of the hormone in most normal subjects. The serum TSH level in normal subjects is 1·6 ± 0·8μU/ml. Patients with non-toxic goitre and acromegaly have normal TSH levels. Values are always raised in hypothyroid patients (with primary thyroid disease) and are significantly lowered in those with hyperthyroidism. Of the many stimuli used in an attempt to raise TSH levels in normal adult subjects only three—synthetic thyrotrophin-releasing hormone, ethinyloestradiol, and carbimazole plus iodides—have been effective. The major clinical application of the TSH immunoassay lies in the diagnosis of minor degrees of hypothyroidism. An impaired response of serum TSH to synthetic thyrotrophin-releasing hormone should also help in the diagnosis of hypopituitarism affecting TSH production. PMID:5548300

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

    McKenzie-Carter, M.A.; Lyon, R.E.

    This report contains information to support the Environmental Assessment for the Compact Ignition Tokamak Project (CIT) proposed for Princeton Plasma Physics Laboratory (PPPL). The assumptions and methodology used to assess the impact to members of the public from operational and accidental releases of radioactive material from the proposed CIT during the operational period of the project are described. A description of the tracer release tests conducted at PPPL by NOAA is included; dispersion values from these tests are used in the dose calculation. Radiological releases, doses, and resulting health risks are calculated. The computer code AIRDOS-EPA is used to calculatemore » the individual and population doses for routine releases; FUSCRAC3 is used to calculate doses resulting from off-normal releases where direct application of the NOAA tracer test data is not practical. Where applicable, doses are compared to regulatory limits and guidelines values. 44 refs., 5 figs., 18 tabs.« less

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

    McKenzie-Carter, M.A.; Lyon, R.E.; Rope, S.K.

    This report contains information to support the Environmental Assessment for the Burning Plasma Experiment (BPX) Project proposed for the Princeton Plasma Physics Laboratory (PPPL). The assumptions and methodology used to assess the impact to members of the public from operational and accidental releases of radioactive material from the proposed BPX during the operational period of the project are described. A description of the tracer release tests conducted at PPPL by NOAA is included; dispersion values from these tests are used in the dose calculations. Radiological releases, doses, and resulting health risks are calculated and summarized. The computer code AIRDOS- EPA,more » which is part of the computer code system CAP-88, is used to calculate the individual and population doses for routine releases; FUSCRAC3 is used to calculate doses resulting from off-normal releases where direct application of the NOAA tracer test data is not practical. Where applicable, doses are compared to regulatory limits and guideline values. 48 refs., 16 tabs.« less

  8. Normalization of doxorubicin release from graphene oxide: New approach for optimization of effective parameters on drug loading.

    PubMed

    Hashemi, Mohadeseh; Yadegari, Amir; Yazdanpanah, Ghasem; Omidi, Meisam; Jabbehdari, Sayena; Haghiralsadat, Fatemeh; Yazdian, Fatemeh; Tayebi, Lobat

    2017-05-01

    Graphene oxide (GO) has been recently introduced as a suitable anticancer drug carrier, which could be loaded with doxorubicin (DOX) as a general chemotherapy agent. Herein, the attempts were made to optimize the effective parameters on both loading and release of DOX on GO. GO and GO-DOX were characterized using transition electron microscopy , zeta potential, Raman spectroscopy, UV-visible spectroscopy, and Fourier transform infrared spectroscopy. In addition, loading and releasing behaviors of DOX on GO were studied in terms of different temperature and pH values. The primary optimized values of pH and temperature for best-loaded amount of DOX were 8.9 and 309 K, respectively. Moreover, we found that the smallest amount of released DOX, in pH of cancer microenvironment (5.4), occurs when DOX had been previously loaded in pH 7.8 and 310 K. Although the highest amount of loaded DOX was in basic pH, the results of efficient release of DOX from the GO-DOX complex and also cellular toxicity assay revealed that the best pH for loading of DOX on GO was 7.8. Therefore, in addition to optimization of parameters for efficient loading of DOX on GO, this study suggested that normalization of a released drug compared with the amount of a loaded drug could be a new approach for optimization of drug loading on nanocarriers. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  9. Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart.

    PubMed

    Pourkhalili, Khalil; Hajizadeh, Sohrab; Akbari, Zahra; Dehaj, Mansour Esmaili; Akbarzadeh, Samad; Alizadeh, Alimohammad

    2012-01-01

    Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

  10. The effect of acute exercise on pulsatile release of luteinizing hormone in women runners.

    PubMed

    Cumming, D C; Vickovic, M M; Wall, S R; Fluker, M R; Belcastro, A N

    1985-11-01

    Endurance exercise has been associated with reproductive dysfunction. We have previously suggested that pulsatile release of luteinizing hormone is impaired at rest in normal menstruating runners compared with sedentary women. To determine whether acute exercise had any effect on pulsatile release of luteinizing hormone we investigated serum luteinizing hormone levels in six normal menstruating runners at rest and after 60 minutes of running exercise. Exercise induced an increment in circulating luteinizing hormone levels greater than the change in hematocrit. The luteinizing hormone pulse frequency, calculated as the number of luteinizing hormone pulses per 6 hours, was reduced after exercise compared with values obtained at rest. There was no significant difference in pulse amplitude or area under the 6-hour curve between resting and postexercise situations. These data suggest that acute exercise has an inhibitory effect on luteinizing hormone pulsatile release at the hypothalamic level in eumenorrheic runners that is in addition to the previously described effect of training.

  11. Time Variation of the Distance Separating Bomb and Dive Bomber Subsequent to Bomb Release

    NASA Technical Reports Server (NTRS)

    Mathews, Charles W.

    1952-01-01

    A study has been made of the variation of the distance separating bomb and aircraft with time after release as applied to dive-bombing operations, Separation distances determined from this study are presented in terms of two variables only, dive angle and maximum airplane accelerometer reading; the values of separation distance include the effects of delay in initiation of the pull-out and lag in attainment of the maximum normal acceleration.Contains analysis and calculations of the separation distances between bomb and dive bomber following bomb release, Separation distances as determined by the dive angle and the maximum airplane accelerometer reading are presented in a single chart.

  12. Effects of myofascial release after high-intensity exercise: a randomized clinical trial.

    PubMed

    Arroyo-Morales, Manuel; Olea, Nicolas; Martinez, Manuel; Moreno-Lorenzo, Carmen; Díaz-Rodríguez, Lourdes; Hidalgo-Lozano, Amparo

    2008-03-01

    The usefulness of massage as a recovery method after high-intensity exercise has yet to be established. We aimed to investigate the effects of whole-body massage on heart rate variability (HRV) and blood pressure (BP) after repeated high-intensity cycling exercise under controlled and standardized pretest conditions. The study included 62 healthy active individuals. After baseline measurements, the subjects performed standardized warm-up exercises followed by three 30-second Wingate tests. After completing the exercise protocol, the subjects were randomly assigned to a massage (myofascial release) or placebo (sham treatment with disconnected ultrasound and magnetotherapy equipment) group for a 40-minute recovery period. Holter recording and BP measurements were taken after exercise protocol and after the intervention. After the exercise protocol, both groups showed a significant decrease in normal-to-normal interval, HRV index, diastolic BP (P > .001), and low-frequency domain values (P = .006). After the recovery period, HRV index (P = .42) and high-frequency (HF) (P = .94) values were similar to baseline levels in the massage group, whereas the HRV index tended (P = .05) to be lower and the HF was significantly (P < .01) lower vs baseline values in the placebo group, which also showed a tendency (P = .06) for HF to be lower than after the exercise. Likewise, diastolic BP returned to baseline levels in the massage group (P = .45) but remained lower in the placebo group (P = .02). Myofascial release massage favors the recovery of HRV and diastolic BP after high-intensity exercise (3 Wingate tests) to preexercise levels.

  13. Hyperfunctioning thyroid nodules in children.

    PubMed

    Abe, K; Konno, M; Sato, T; Matsuura, N

    1980-10-01

    We studied two cases of hyperfunctioning thyroid nodules in children. A 9-year-old girl and an 11-year-old girl had thyroid masses in otherwise nonpalpable thyroid glands. Scintiscan showed hyperfunctioning thyroid nodules. The former patient had elevated values for T4 and T3, and plasma thyrotropin (TSH) level failed to respond to stimulation with thyrotropin releasing hormone (TRH), whereas the latter patient had normal values for T4, and T3 and plasma TSH response to TRH was normal. After the surgical removal of nodules, scintiscan exhibited radioactivity in the contralateral lobe of the thyroid gland in the former and in the ectopic thyroid tissue in the latter. Results of microscopic examinations of thyroid nodules were consistent with adenomatous goiter.

  14. Changes of insulin resistance and β-cell function in women with gestational diabetes mellitus and normal pregnant women during mid- and late pregnant period: a case-control study.

    PubMed

    Wang, Yun-Hui; Wu, Hui-Hua; Ding, Hong; Li, Yan; Wang, Zhen-Hua; Li, Feng; Zhang, Jian-Ping

    2013-03-01

    The aim of this study was to observe insulin resistance and β-cell function changes among women diagnosed with gestational impaired glucose tolerance or gestational diabetes mellitus (GDM) in mid-pregnancy. Sixty-four pregnant women receiving prenatal care underwent an oral glucose tolerance test at 20-24 weeks of gestation and an insulin release test. The GDM group included 34 pregnant women diagnosed with gestational impaired glucose tolerance or GDM, and the subjects with normal blood glucose were the control group. Insulin resistance and islet β-cell function changes were observed with the oral glucose tolerance test and insulin release test. The homeostatic model assessment-β levels in late pregnancy were higher than those in mid-pregnancy for both groups, and the primary time effect was statistically significant. The early insulin secretion index (ΔI(30)/ΔG(30)) values in mid- and late pregnancy were lower in the GDM group. The values of the area under the curve of blood glucose in mid- and late pregnancy were higher in the GDM group than those in the control group. Insulin resistance was higher in GDM patients than in normal pregnant women. Insulin resistance was aggravated, and β-cell's ability to compensate for the increased insulin resistance by modulating insulin secretion was aggravated, as gestational week increased in women with gestational diabetes and normal pregnant women. Insulin resistance in women with GDM is higher than in pregnant women with normal metabolism of glucose. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  15. Normal fault earthquakes or graviquakes

    PubMed Central

    Doglioni, C.; Carminati, E.; Petricca, P.; Riguzzi, F.

    2015-01-01

    Earthquakes are dissipation of energy throughout elastic waves. Canonically is the elastic energy accumulated during the interseismic period. However, in crustal extensional settings, gravity is the main energy source for hangingwall fault collapsing. Gravitational potential is about 100 times larger than the observed magnitude, far more than enough to explain the earthquake. Therefore, normal faults have a different mechanism of energy accumulation and dissipation (graviquakes) with respect to other tectonic settings (strike-slip and contractional), where elastic energy allows motion even against gravity. The bigger the involved volume, the larger is their magnitude. The steeper the normal fault, the larger is the vertical displacement and the larger is the seismic energy released. Normal faults activate preferentially at about 60° but they can be shallower in low friction rocks. In low static friction rocks, the fault may partly creep dissipating gravitational energy without releasing great amount of seismic energy. The maximum volume involved by graviquakes is smaller than the other tectonic settings, being the activated fault at most about three times the hypocentre depth, explaining their higher b-value and the lower magnitude of the largest recorded events. Having different phenomenology, graviquakes show peculiar precursors. PMID:26169163

  16. Bilateral phacoemulsification and intraocular lens implantation in a great horned owl.

    PubMed

    Carter, Renee T; Murphy, Christopher J; Stuhr, Charles M; Diehl, Kathryn A

    2007-02-15

    A great horned owl of estimated age < 1 year that was captured by wildlife rehabilitators was evaluated because of suspected cataracts. Nuclear and incomplete cortical cataracts were evident in both eyes. Ocular ultrasonography revealed no evidence of retinal detachment, and electroretinography revealed normal retinal function. For visual rehabilitation, cataract surgery was planned and intraocular lens design was determined on the basis of values obtained from the schematic eye, which is a mathematical model representing a normal eye for a species. Cataract surgery and intraocular lens placement were performed in both eyes. After surgery, refraction was within -0.75 diopters in the right eye and -0.25 diopters in the left eye. Visual rehabilitation was evident on the basis of improved tracking and feeding behavior, and the owl was eventually released into the wild. In raptors with substantial visual compromise, euthanasia or placement in a teaching facility is a typical outcome because release of such a bird is unacceptable. Successful intraocular lens implantation for visual rehabilitation and successful release into the wild are achievable.

  17. Different growth hormone (GH) response to GH-releasing peptide and GH-releasing hormone in hyperthyroidism.

    PubMed

    Ramos-Dias, J C; Pimentel-Filho, F; Reis, A F; Lengyel, A M

    1996-04-01

    Altered GH responses to several pharmacological stimuli, including GHRH, have been found in hyperthyroidism. The mechanisms underlying these disturbances have not been fully elucidated. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release both in vitro and in vivo. The mechanism of action of GHRP-6 is unknown, but it probably acts by inhibiting the effects of somatostatin on GH release. The aim of this study was to evaluate the effects of GHRP-6 on GH secretion in patients with hyperthyroidism (n = 9) and in control subjects (n = 9). Each subject received GHRP-6 (1 microg/kg, iv), GHRH (100 microg, iv), and GHRP-6 plus GHRH on 3 separate days. GH peak values (mean +/- SE; micrograms per L) were significantly lower in hyperthyroid patients compared to those in control subjects after GHRH alone (9.0 +/- 1.3 vs. 27.0 +/- 5.2) and GHRP-6 plus GHRH (22.5 +/- 3.5 vs. 83.7 +/- 15.2); a lack of the normal synergistic effect of the association of both peptides was observed in thyrotoxicosis. However, a similar GH response was seen in both groups after isolated GHRP-6 injection (31.9 +/- 5.7 vs. 23.2 +/- 3.9). In summary, we have shown that hyperthyroid patients have a normal GH response to GHRP-6 together with a blunted GH responsiveness to GHRH. Our data suggest that thyroid hormones modulate GH release induced by these two peptides in a differential way.

  18. Glucose and Insulin Secretory Response Patterns Following Diet and Tolazamide Therapy in Diabetes

    PubMed Central

    Turtle, J. R.

    1970-01-01

    Glucose and insulin secretory response patterns during glucose tolerance tests were determined in 28 maturity-onset diabetics, and the sequential effects of diet and a sulphonylurea, tolazamide, were assessed. Untreated diabetics showed hyperglycaemia, increased serum immunoreactive insulin response patterns, delayed insulin release, and relative insulin deficiency. Diet alone partially corrected the hyperglycaemia and serum immunoreactive insulin response but had no effect on the delayed insulin release or relative insulin deficiency. Tolazamide plus diet restored all values towards normal. The net effect of maintenance tolazamide therapy was to (1) restore the insulin secretory response pattern to normal, (2) reduce total pancreatic insulin output, and (3) improve the efficiency of insulin secretion. The results suggest that there is a rational basis for the use of sulphonylurea in all maturity-onset diabetics, including patients with mild carbohydrate intolerance and those who are apparently controlled by diet alone. PMID:5470087

  19. Effect of decrease in both postprandial blood glucose (PBG) and fasting blood glucose (FBG) levels in normal beagle dogs with nateglinide enteric coated granules and immediate release tablets.

    PubMed

    Makino, Chisato; Ninomiya, Nobutaka; Sakai, Hidetoshi; Orita, Haruo; Okano, Akira; Yabuki, Akira

    2006-04-01

    Nateglinide is a new quick action/short duration (QRSD) type of oral blood glucose regulator, and nateglinide immediate release tablets are used for patients with mild diabetes under the trade name of Fastic((R)) tablets. In this study, we attempted to determine if it was possible to control both post-prandial blood glucose level (PBG) and fasting blood glucose level (FBG) for moderate or severe diabetes through controlled release of nateglinide. Enteric coated granules were selected for the administration form for controlled release of nateglinide, and three types of enteric coated granules were prepared having dissolution pH values of 5.5, 6.5 and 7.2. The three types of enteric coated granules were each administered separately or the enteric coated granules having an dissolution pH of 6.5 were administered simultaneous to administration of nateglinide immediate release tablets to normal beagle dogs just before feeding followed by measurement of plasma nateglinide concentration, plasma insulin concentration and blood glucose level. In the case of administering enteric coated granules alone (nateglinide: 9 mg/kg), the absorption of nateglinide was confirmed to tend to be delayed as the dissolution pH increased. In the case of an dissolution pH of 5.5, decreases in both PBG and FBG were observed. In the case of dissolution pH values of 6.5 and 7.2, only decrease in FBG was observed. In case of nateglinide immediate release tablets (nateglinide: 9 mg/kg), only decrease in PBG was observed. Decreases in both PBG and FBG were observed in the case of simultaneous administration of dissolution pH 6.5 enteric coated granules and nateglinide immediate release tablets just before feeding (nateglinide: 90 mg/head+60 mg/head). A correlation was observed between plasma nateglinide concentrations and blood glucose levels. On the other hand, there were no correlations observed between changes in plasma insulin concentrations and blood glucose levels. In case of nateglinide immediate release tablets (nateglinide: 150 mg/head), Decreases in both PBG and FBG were observed. However, the nateglinide controlled release formulation is more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, or of easy control of both PBG and FBG. On the basis of these results, the design of a controlled release formulation that contains nateglinide was suggested to enable control of both PBG and FBG for moderate and severe diabetes patients.

  20. Controlled drug release by polymer dissolution. II: Enzyme-mediated delivery device.

    PubMed

    Heller, J; Trescony, P V

    1979-07-01

    A novel, closed-loop drug delivery system was developed where the presence or absence of an external compound controls drug delivery from a bioerodible polymer. In the described delivery system, hydrocortisone was incorporated into a n-hexyl half-ester of a methyl vinyl ehter-maleic anhydride copolymer, and the polymer-drug mixture was fabricated into disks. These disks were then coated with a hydrogel containing immobilized urease. In a medium of constant pH and in the absence of external urea, the hydrocortisone release was that normally expected for that polymer at the given pH. With external urea, ammonium bicarbonate and ammonium hydroxide were generated within the hydrogel, which accelerated polymer erosion and drug release. The drug delivery rate increase was proportional to the amount of external urea and was reversible; that is, when external urea was removed, the drug release rate gradually returned to its original value.

  1. Kinetics of dissolution of thorium and uranium doped britholite ceramics

    NASA Astrophysics Data System (ADS)

    Dacheux, N.; Du Fou de Kerdaniel, E.; Clavier, N.; Podor, R.; Aupiais, J.; Szenknect, S.

    2010-09-01

    In the field of immobilization of actinides in phosphate-based ceramics, several thorium and uranium doped britholite samples were submitted to leaching tests. The normalized dissolution rates determined for several pH values, temperatures and acidic media from the calcium release range from 4.7 × 10 -2 g m -2 d -1 to 21.6 g m -2 d -1. Their comparison with that determined for phosphorus, thorium and uranium revealed that the dissolution is clearly incongruent for all the conditions examined. Whatever the leaching solution considered, calcium and phosphorus elements were always released with higher RL values than the other elements (Nd, Th, U). Simultaneously, thorium was found to quickly precipitate as alteration product, leading to diffusion phenomena for uranium. For all the media considered, the uranium release is higher than that of thorium, probably due to its oxidation from tetravalent oxidation state to uranyl. Moreover, the evaluation of the partial order related to proton concentration and the apparent energy of activation suggest that the reaction of dissolution is probably controlled by surface chemical reactions occurring at the solid/liquid interface. Finally, comparative leaching tests performed in sulphuric acid solutions revealed a significant influence of such media on the chemical durability of the leached pellets, leading to higher normalized dissolution rates for all the elements considered. On the basis of the results of chemical speciation, this difference was mainly explained in the light of higher complexion constants by sulfate ions compared to nitrate, chloride and phosphate.

  2. Transport mechanism of L-[14C]glutamate in cortical slices and synaptosomes of rabbits exposed to brain ischemia and reperfusion.

    PubMed

    Solyakov, L; Dobrota, D; Drany, O; Vachova, M; Machac, S; Mezesova, V; Bachurin, S; Lombardi, V

    1995-01-01

    Changes in the functioning of the glutamatergic system in rabbit brain were studied after partial brain ischemia and reperfusion. In vitro studies were conducted relating to the release of L-[14C]glutamate from cortical brain slices, L-[14C]glutamate uptake in synaptosomes, and 45Ca uptake in synaptosomes. It was found that basal release of L-[14C]glutamate from rabbit brain cortical slices after 30 min of partial ischemia and 1 d of reperfusion was essentially without change compared to the control values. After 3 d of reperfusion, there was an increase in basal release of L-[14C]glutamate from rabbit brain cortical slices. K+ stimulated release of L-[14C]glutamate in normal Krebs-Ringer medium was essentially the same in the control group and in the experimental group after 30 min of ischemia. The K+ stimulated release of L-[14C]glutamate independent of calcium was increased to 145% after 30 min of ischemia and 1 d of reperfusion. The decreased Km value at the glutamate transporter may have contributed to this difference. Kinetic parameters of the L-[14C]glutamate uptake (Km and Vmax) in synaptosomes from rabbit brain were significantly lower after 30 min of ischemia. The authors discovered that during the reperfusion period, Vmax was almost the same as in the control group. The activity of the Na+/Ca2+ exchanger in synaptosomes of rat brain was about 70% of the control values after 30 min of ischemia and 72 h of reperfusion. According to our results, increased L-[14C]glutamate release after 30 min of ischemia appears to be the result of higher intracellular calcium concentration and possibly also of a higher uptake of glutamate.

  3. Step-wise supercritical extraction of carbonaceous residua

    DOEpatents

    Warzinski, Robert P.

    1987-01-01

    A method of fractionating a mixture containing high boiling carbonaceous material and normally solid mineral matter includes processing with a plurality of different supercritical solvents. The mixture is treated with a first solvent of high critical temperature and solvent capacity to extract a large fraction as solute. The solute is released as liquid from solvent and successively treated with other supercritical solvents of different critical values to extract fractions of differing properties. Fractionation can be supplemented by solute reflux over a temperature gradient, pressure let down in steps and extractions at varying temperature and pressure values.

  4. Muscle activation and the isokinetic torque-velocity relationship of the human triceps surae.

    PubMed

    Harridge, S D; White, M J

    1993-01-01

    The influence of muscle activation and the time allowed for torque generation on the angle-specific torque-velocity relationship of the triceps surae was studied during plantar flexion using supramaximal electrical stimulation and a release technique on six male subjects [mean (SD) age 25 (4) years]. Torque-velocity data were obtained under different levels of constant muscle activation by varying the stimulus frequency and the time allowed for isometric torque generation prior to release and isokinetic shortening. To eliminate the effects of the frequency response on absolute torque the isokinetic data were normalized to the maximum isometric torque values at 0.44 rad. There were no significant differences in the normalized torques generated at any angular velocity using stimulus frequencies of 20, 50 or 80 Hz. When the muscle was stimulated at 50 Hz the torques obtained after a 400 ms and 1 s pre-release isometric contraction did not differ significantly. However, with no pre-release contraction significantly less torque was generated at all angular velocities beyond 1.05 rad.s-1 when compared with either the 200, 400 ms or 1 s condition. With a 200 ms pre-release contraction significantly less torque was generated at angular velocities beyond 1.05 rad.s-1 when compared with the 400 ms or 1 s conditions. It would seem that the major factor governing the shape of the torque-velocity curve at a constant level of muscle activation is the time allowed for torque generation.

  5. Neural-network-based state of health diagnostics for an automated radioxenon sampler/analyzer

    NASA Astrophysics Data System (ADS)

    Keller, Paul E.; Kangas, Lars J.; Hayes, James C.; Schrom, Brian T.; Suarez, Reynold; Hubbard, Charles W.; Heimbigner, Tom R.; McIntyre, Justin I.

    2009-05-01

    Artificial neural networks (ANNs) are used to determine the state-of-health (SOH) of the Automated Radioxenon Analyzer/Sampler (ARSA). ARSA is a gas collection and analysis system used for non-proliferation monitoring in detecting radioxenon released during nuclear tests. SOH diagnostics are important for automated, unmanned sensing systems so that remote detection and identification of problems can be made without onsite staff. Both recurrent and feed-forward ANNs are presented. The recurrent ANN is trained to predict sensor values based on current valve states, which control air flow, so that with only valve states the normal SOH sensor values can be predicted. Deviation between modeled value and actual is an indication of a potential problem. The feed-forward ANN acts as a nonlinear version of principal components analysis (PCA) and is trained to replicate the normal SOH sensor values. Because of ARSA's complexity, this nonlinear PCA is better able to capture the relationships among the sensors than standard linear PCA and is applicable to both sensor validation and recognizing off-normal operating conditions. Both models provide valuable information to detect impending malfunctions before they occur to avoid unscheduled shutdown. Finally, the ability of ANN methods to predict the system state is presented.

  6. Is liver SUV stable over time in ¹⁸F-FDG PET imaging?

    PubMed

    Laffon, Eric; Adhoute, Xavier; de Clermont, Henri; Marthan, Roger

    2011-12-01

    This work investigated whether (18)F-FDG PET standardized uptake value (SUV) is stable over time in the normal human liver. The SUV-versus-time curve, SUV(t), of (18)F-FDG in the normal human liver was derived from a kinetic model analysis. This derivation involved mean values of (18)F-FDG liver metabolism that were obtained from a patient series (n = 11), and a noninvasive population-based input function was used in each individual. Mean values (±95% reliability limits) of the (18)F-FDG uptake and release rate constant and of the fraction of free tracer in blood and interstitial volume were as follows: K = 0.0119 mL·min(-1)·mL(-1) (±0.0012), k(R) = 0.0065·min(-1) (±0.0009), and F = 0.21 mL·mL(-1) (±0.11), respectively. SUV(t) (corrected for (18)F physical decay) was derived from these mean values, showing that it smoothly peaks at 75-80 min on average after injection and that it is within 5% of the peak value between 50 and 110 min after injection. In the normal human liver, decay-corrected SUV(t) remains nearly constant (with a reasonable ±2.5% relative measurement uncertainty) if the time delay between tracer injection and PET acquisition is in the range of 50-110 min. In current clinical practice, the findings suggest that SUV of the normal liver can be used for comparison with SUV of suspected malignant lesions, if comparison is made within this time range.

  7. Increased mast cell density in haemorrhoid venous blood vessels suggests a role in pathogenesis.

    PubMed

    Taweevisit, M; Wisadeopas, N; Phumsuk, U; Thorner, P S

    2008-12-01

    Haemorrhoids are an abnormal, tortuous dilatation of the arteriovenous plexus of the anus. Although increased resting anorectal pressure is deemed to be a major initiating factor, a thorough understanding of the pathogenesis is still lacking. Mast cells, through release of granules, can affect local vessels with respect to changes in calibre, changes in permeability and thrombosis. Thus, mast cells could play a role in haemorrhoid pathophysiology, although this has not been previously investigated. 48 cases of haemorrhoids were retrospectively collected at King Chulalongkorn Memorial Hospital, with normal anorectal tissue from surgically-removed colorectal cancer serving as controls. Mast cells were identified by toluidine blue staining and quantitated around venous vessels. Mast cells around haemorrhoidal vessels were significantly more numerous than in normal specimens (p-value is less than 0.001). Similar values were found for haemorrhoids showing chronic changes and those in a more acute stage. These findings support the hypothesis that mast cells may play a role in the pathophysiology of haemorrhoids. Mast cells appear to participate equally in the early and later stages of these lesions. Mast cells are known to affect local vascular conditions through release of their chemical mediators and cytokines, and may influence haemorrhoid symptomatology and progression at this level.

  8. Distribution Development for STORM Ingestion Input Parameters

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

    Fulton, John

    The Sandia-developed Transport of Radioactive Materials (STORM) code suite is used as part of the Radioisotope Power System Launch Safety (RPSLS) program to perform statistical modeling of the consequences due to release of radioactive material given a launch accident. As part of this modeling, STORM samples input parameters from probability distributions with some parameters treated as constants. This report described the work done to convert four of these constant inputs (Consumption Rate, Average Crop Yield, Cropland to Landuse Database Ratio, and Crop Uptake Factor) to sampled values. Consumption rate changed from a constant value of 557.68 kg / yr tomore » a normal distribution with a mean of 102.96 kg / yr and a standard deviation of 2.65 kg / yr. Meanwhile, Average Crop Yield changed from a constant value of 3.783 kg edible / m 2 to a normal distribution with a mean of 3.23 kg edible / m 2 and a standard deviation of 0.442 kg edible / m 2 . The Cropland to Landuse Database ratio changed from a constant value of 0.0996 (9.96%) to a normal distribution with a mean value of 0.0312 (3.12%) and a standard deviation of 0.00292 (0.29%). Finally the crop uptake factor changed from a constant value of 6.37e -4 (Bq crop /kg)/(Bq soil /kg) to a lognormal distribution with a geometric mean value of 3.38e -4 (Bq crop /kg)/(Bq soil /kg) and a standard deviation value of 3.33 (Bq crop /kg)/(Bq soil /kg)« less

  9. Inflammation Promotes Airway Epithelial ATP Release via Calcium-Dependent Vesicular Pathways

    PubMed Central

    Okada, Seiko F.; Ribeiro, Carla M. P.; Sesma, Juliana I.; Seminario-Vidal, Lucia; Abdullah, Lubna H.; van Heusden, Catharina; Lazarowski, Eduardo R.

    2013-01-01

    ATP in airway surface liquid (ASL) controls mucociliary clearance functions via the activation of airway epithelial purinergic receptors. However, abnormally elevated ATP levels have been reported in inflamed airways, suggesting that excessive ATP in ASL contributes to airway inflammation. Despite these observations, little is known about the mechanisms of ATP accumulation in the ASL covering inflamed airways. In this study, links between cystic fibrosis (CF)–associated airway inflammation and airway epithelial ATP release were investigated. Primary human bronchial epithelial (HBE) cells isolated from CF lungs exhibited enhanced IL-8 secretion after 6 to 11 days, but not 28 to 35 days, in culture, compared with normal HBE cells. Hypotonic cell swelling–promoted ATP release was increased in 6- to 11-day-old CF HBE cells compared with non-CF HBE cells, but returned to normal values after 28 to 35 days in culture. The exposure of non-CF HBE cells to airway secretions isolated from CF lungs, namely, sterile supernatants of mucopurulent material (SMM), also caused enhanced IL-8 secretion and increased ATP release. The SMM-induced increase in ATP release was sensitive to Ca2+ chelation and vesicle trafficking/exocytosis inhibitors, but not to pannexin inhibition. Transcript levels of the vesicular nucleotide transporter, but not pannexin 1, were up-regulated after SMM exposure. SMM-treated cultures displayed increased basal mucin secretion, but mucin secretion was not enhanced in response to hypotonic challenge after the exposure of cells to either vehicle or SMM. We propose that CF airway inflammation up-regulates the capacity of airway epithelia to release ATP via Ca2+-dependent vesicular mechanisms not associated with mucin granule secretion. PMID:23763446

  10. Preparation and evaluation of periodontal films based on polyelectrolyte complex formation.

    PubMed

    Kassem, Abeer Ahmed; Ismail, Fatma Ahmed; Naggar, Viviane Fahim; Aboulmagd, Elsayed

    2015-05-01

    Local intra-pocket drug delivery devices can provide an effective concentration of the antimicrobial agent at the site of action with avoidance of undesirable side effects. This study explored the application of chitosan-alginate and chitosan-pectin polyelectrolyte complex (PEC) films as drug release regulators for tetracycline HCl (Tc) to treat periodontal pockets. Periodontal films with 1:1 Tc:PEC ratio were prepared using 1:1 chitosan (Ch) to sodium alginate (A) or 1:3 Ch to pectin (P). The scanning electron microscope showed acceptable film appearance and differential scanning calorimetry analysis confirmed complex formation. The in vitro release studies for both films showed a burst drug release, followed by prolonged release for 70 h. A prolonged antibacterial activity of both films against Staphylococcus aureus ATCC 6538 was observed over a period of 21 days. Aging studies indicated that the five months storage period in freezer did not significantly influence the drug release profile or the antibacterial activity of both films. Clinical evaluation showed a significant reduction in pocket depth (p < 0.0001) to their normal values (≤3 mm). PEC films could be exploited as a prolonged drug release devices for treatment of periodontal pockets.

  11. The hypothalamic paraventricular nucleus has a pivotal role in regulation of prolactin release in lactating rats.

    PubMed

    Kiss, J Z; Kanyicska, B; Nagy, G Y

    1986-08-01

    The affect of paraventricular nucleus (PVN) lesions on PRL secretory response to suckling was studied in adult female rats. Basal levels of PRL were similar in the control and lesioned groups. Substantial decreases in PRL levels occurred after separation of pups from their mothers in the control as well as lesioned animals. When mothers and pups were reunited, the circulating PRL concentrations of the control groups rose immediately from basal values of 50-100 micrograms/liter to reach peaks of 450-550 micrograms/liter. PVN lesions significantly decreased the suckling-induced rise of PRL levels. Furthermore, PVN lesions abolished the high amplitude, episodic pattern of PRL release in continuously lactating rats. These findings are consistent with the view that PVN neurons produce PRL releasing factor(s), which is (are) required for normal secretory patterns of PRL in lactating rats.

  12. Preparation and In Vitro/In Vivo Evaluation of Vinpocetine Elementary Osmotic Pump System

    PubMed Central

    Ning, Meiying; Zhou, Yue; Chen, Guojun; Mei, Xingguo

    2011-01-01

    Preparation and in vitro and in vivo evaluation of vinpocetine (VIN) elementary osmotic pump (EOP) formulations were investigated. A method for the preparation of VIN elementary osmotic pump tablet was obtained by adding organic acid additives to increase VIN solubility. VIN was used as the active pharmaceutical ingredient, lactose and mannitol as osmotic agent. Citric acid was used as increasing API solubility and without resulting in the API degradation. It is found that the VIN release rate was increasing with the citric acid amount at a constant range. Cellulose acetate 398-3 was employed as semipermeable membrane containing polyethylene glycol 6000 and diethyl-o-phthalate as pore-forming agent and plasticizer for controlling membrane permeability. In addition, a clear difference between the pharmacokinetic patterns of VIN immediate release and VIN elementary osmotic pump formulations was revealed. The area under the plasma concentration-time curve after oral administration of elementary osmotic pump formulations was equivalent to VIN immediate release formulation. Furthermore, significant differences found for mean residence time, elimination half-life, and elimination rate constant values corroborated prolonged release of VIN from elementary osmotic pump formulations. These results suggest that the VIN osmotic pump controlled release tablets have marked controlled release characters and the VIN osmotic pump controlled release tablets and the normal tablets were bioequivalent. PMID:21577257

  13. Normal results of post-race thallium-201 myocardial perfusion imaging in marathon runners with elevated serum MB creatine kinase levels

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

    Siegel, A.J.; Silverman, L.M.; Holman, B.L.

    1985-10-01

    Elevated cardiac enzyme values in asymptomatic marathon runners after competition can arise from skeletal muscle through exertional rhabdomyolysis, silent injury to the myocardium, or a combined tissue source. Peak post-race levels of the MB isoenzyme of creatine kinase are similar to values in patients with acute myocardial infarction. Previously reported normal results of infarct-avid myocardial scintigraphy with technetium 99m pyrophosphate in runners after competition suggest a non-cardiac source but cannot exclude silent injury to the myocardium. Therefore, thallium 201 myocardial perfusion imaging was performed in runners immediately after competition together with determination of sequential cardiac enzyme levels. Among 15 runnersmore » tested, the average peak in serum MB creatine kinase 24 hours after the race was 128 IU/liter with a cumulative MB creatine kinase release of 117 IU/liter; these values are comparable to those in patients with acute transmural myocardial infarction. Thallium 201 myocardial scintigraphic results were normal in five runners randomly selected from those who volunteered for determination of sequential blood levels. It is concluded that elevations of serum MB creatine kinase in marathon runners arise from a skeletal muscle source and that thallium 201 myocardial scintigraphy is useful to assess runners for myocardial injury when clinical questions arise.« less

  14. GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in Obese Patients with Fibromyalgia Syndrome.

    PubMed

    Rigamonti, Antonello E; Grugni, Graziano; Arreghini, Marco; Capodaglio, Paolo; De Col, Alessandra; Agosti, Fiorenza; Sartorio, Alessandro

    2017-01-01

    Reportedly, fibromyalgia (FM) is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or <-2 SDS), underwent the combined GHRH plus arginine test. Four out of 16 obese women with FM (25%) had low IGF-1 SDS values, 2 cases of this subgroup (12.5%) failing also to normally respond to the test. Among patients with normal GH responses, 4 showed a delayed GH peak. The subgroup with low IGF-1 SDS values had higher BMI than that with normal IGF-1 SDS. GH peak and area under the curve were not correlated with CRP, ESR, or tender point score, while significant correlations were found with fat-free mass and fat mass. In conclusion, this study shows the existence of a high prevalence of GH-IGF-1 dysfunction in patients with both FM and obesity, presumably as a consequence of the obese rather than fibromyalgic condition.

  15. Fixation Release and the Bone Bandaid: A New Bone Fixation Device Paradigm

    PubMed Central

    Shayesteh Moghaddam, Narges; Jahadakbar, Ahmadreza; Amerinatanzi, Amirhesam; Skoracki, Roman; Miller, Michael; Dean, David; Elahinia, Mohammad

    2017-01-01

    The current gold standard of care for mandibular segmental defeat reconstruction is the use of Ti-6Al-4V immobilization hardware and fibular double barrel graft. This method is often successful immediately at restoring mandible function, however the highly stiff fixation hardware causes stress shielding of the grafted bone and stress concentration in the fixation device over time which can lead to fixation device failure and revision surgery. The purpose of reconstructive surgery could be to create normal stress trajectories in the mandible following engraftment. We investigate the use of a two stage mechanism which separates the immobilization/healing and regenerative phases of mandibular segmental defect treatment. The device includes the use of a very stiff, Ti-6Al-4V, releasable mechanism which assures bone healing. Therefore it could be released once the reconstructed boney tissue and any of its ligamentous attachments have completely healed. Underneath the released Ti-6Al-4V plate would be a pre-loaded nitinol (NiTi) wire-frame apparatus that facilitates the normal stress-strain trajectory through the engrafted bone after the graft is healed in place and the Ti-6Al-4V fixation device has been released. Due to the use of NiTi wires forming a netting that connects vascularized bone and possibly bone chips, bone grafts are also more likely to be incorporate rather than to resorb. We first evaluated a healthy adult mandible during normal mastication to obtain the normal stress-strain distribution. Then, we developed the finite element (FE) model of the mandibular reconstruction (in the M1-3 region) with the proposed fixation device during the healing (locked state) and post-healing (released state) periods. To recreate normal stress trajectory in the reconstructed mandible, we applied the Response Surface Methodology (RMS) to optimize the Bone Bandaid geometry (i.e., wire diameters and location). The results demonstrate that the proposed mechanism immobilizes the grafted bone in the locked state properly since the maximum resultant gap (21.54 micron) between the graft and host mandible surfaces are in the safe region (less than 300 micron). By considering the von Mises criteria for failure, FE analysis together with experimental studies (i.e., compressive and tensile testing on the inferior and superior fixation devices, respectively) confirm that the proposed fixation devices do not fail, showing safety factor of at least 10.3. Based on the Response Surface Methodology (RSM) technique, the optimal parameter values for the wires are achieved (0.65 mm and 1 mm for the superior and inferior wires, respectively) and the required level of preload on each wire are calculated (369.8 N and 229 N for the inferior and superior wires, respectively). The FE results for stress distribution on the reconstructed mandible during the released state closely match that of a healthy mandible. PMID:28952484

  16. Calcium channel blockers and transmitter release at the normal human neuromuscular junction.

    PubMed

    Protti, D A; Reisin, R; Mackinley, T A; Uchitel, O D

    1996-05-01

    Transmitter release evoked by nerve stimulation is highly dependent on Ca2+ entry through voltage-activated plasma membrane channels. Calcium influx may be modified in some neuromuscular diseases like Lambert-Eaton syndrome and amyotrophic lateral sclerosis. We studied the pharmacologic sensitivity of the transmitter release process to different calcium channel blockers in normal human muscles and found that funnel web toxin and omega-Agatoxin-IVA, both P-type calcium channel blockers, blocked nerve-elicited muscle action potentials and inhibited evoked synaptic transmission. The transmitter release was not affected either by nitrendipine, an L-type channel blocker, or omega-Conotoxin-GVIA, an N-type channel blocker. The pharmacologic profile of neuromuscular transmission observed in normal human muscles indicates that P-like channels mediate transmitter release at the motor nerve terminals.

  17. Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats.

    PubMed

    Adeghate, Ernest; Ponery, Abdul Samad

    2004-12-01

    To examine the effect of ipamorelin (IPA), a novel pentapeptide with a strong growth hormone releasing potency, on insulin secretion from pancreatic tissue fragments of normal and diabetic rats. Diabetes mellitus was induced by streptozotocin (60 mg kg(-1)). Four weeks after the induction of diabetes, pancreatic tissue fragments of normal and diabetic rats were removed and incubated with different concentrations (10(-12) - 10(-6) M) of IPA. Insulin release from the pancreas was measured by radioimmunoassay. Ipamorelin evoked significant (p<0.04) increases in insulin secretion from the pancreas of normal and diabetic rats. Either diltiazem or yohimbine or propranolol or a combination of atropine, propranolol and yohimbine inhibited IPA-evoked insulin secretion significantly (p<0.03) from the pancreas of normal and diabetic rats. Atropine caused a significant (p<0.007) reduction in the IPA-induced insulin secretion in diabetic but not in normal rats. IPA stimulates insulin release through the calcium channel and the adrenergic receptor pathways. This is the first study to examine the effect of ipamorelin on insulin secretion in the pancreas.

  18. Mechanisms of iodine release from iodoapatite in aqueous solution

    NASA Astrophysics Data System (ADS)

    Zhang, Z.; Wang, J.

    2017-12-01

    Immobilization of iodine-129 with waste forms in geological setting is challenging due to its extremely long half-life and high volatility in the environment. To evaluate the long-term performance of waste form, it is imperative to determine the release mechanism of iodine hosted in the waste form materials. This study investigated the iodine released from apatite structured waste form Pb9.85 (VO4)6 I1.7 to understand how diffusion and dissolution control the durability of apatite waste form. A standard semi-dynamic leach test was adopted in this study. Samples were exposed in fresh leachant periodically and the leachant was replaced after each interval. Each experiment was carried out in cap-sealed Teflon vessels under constant temperature (e.g. 90 °C). ICP-MS analysis on the reacted leachates shows that Pb and V were released constantly and congruently with the stoichiometric ratio of Pb/V. However, iodine release is incongruent and time dependent. The iodine release rate starts significantly higher than the corresponding stoichiometric value and gradually decreases, approaching the stoichiometric value. Therefore, a dual-mode mechanism is proposed to account for the iodine release from apatite, which is dominated by short-term diffusion and long-term dissolution processes. Additional tests show that the element release rates depend on a number of test parameters, including sample surface to solution volume ratio (m-1), interval (day), temperature (°C), and solution pH. This study provides a quantitative characterization of iodine release mechanism. The activation energy of iodine leaching 21±1.6 kJ/mol was obtained by varying the test temperature. At the test conditions of to neutral pH and 90 °C, the long-term iodine release rate 3.3 mg/(m2 • day) is projected by normalizing sample surface area to solution volume ratio (S/V) to 1.0 m-1 and interval to 1 day. These findings demonstrate i) the feasibility of our approach to quantify the release mechanism and ii) the performance of iodine apatite as a favorable waste form candidate for I-129 disposal.

  19. Dorsal aorta catheterization in rainbow trout (Salmo gairdneri) I. Its validity in the study of blood gonadotropin patterns.

    PubMed

    Zohar, Y

    1980-01-01

    The use of a dorsal aorta catheterization technique to study gonadotropin secretion patterns in the rainbow trout was tested. Heparin used to flush the cannula between repetitive samplings did not have any effect on plasma GTH levels. Catheterization resulted in a slight short-term change in those levels. The gonadotropin levels returned to their initial values as soon as 30 min to 6 hrs after the operation. From then on, the GTH levels remained close to the initial values in fish exhibiting normal feeding behaviour, whereas they tended to decrease in "stressed" females which did not eat normally. The fish which adapted well to dorsal aortic catheterization did not show any changes in the diurnal pattern of GTH levels or in normal gonadal function and GTH profiles during the processes of oocyte maturation and ovulation. It is concluded that individual catheterized trout can be used advantageously for studying gonadotropin secretion patterns after a 3-day recovery period and the elimination of those fish which neither resume normal feeding nor return to initial, pre-operative GTH levels. Using this technique, it was demonstrated that hypophysial GTH release in trout with oocytes undergoing active vitellogenesis is probably effected by short-term bursts (pulses) of secretion.

  20. Right Ventricular Tissue Doppler Assessment in Space During Circulating Volume Modification using the Braslet-M Device

    NASA Technical Reports Server (NTRS)

    Hamilton, D. R.; Sargsyan, A. E.; Fincke, E. M.; Magnus, S. H.; Lonchakov, Y. V.; Alferova, I. V.; Dulchavsky, S. A.; Ebert, D.; Garcia, K.; Martin, D.; hide

    2009-01-01

    This joint U.S. - Russian work aims to establish a methodology for assessing cardiac function in microgravity in association with manipulation of central circulating volume. Russian Braslet-M occlusion cuffs were used to temporarily increase the volume of blood in the lower extremities, which effectively reduces the volume returning to the heart in the central circulation. A novel methodology was tested on the International Space Station (ISS) to assess the volume status of crewmembers by evaluating the responses to application and release of the Braslet-on-occlusion cuffs, as well as to modified Valsalva and Mueller maneuvers. Baseline echocardiographic tissue Doppler imaging (TDI) of the right ventricular free wall with no Braslet applied shows early diastolic E' (16 cm/sec), late diastolic A' (14 cm/sec), and systolic (12 cm/sec) velocities compatible with normal subjects on Earth. TDI of the RV free wall with Braslet applied shows that early diastolic E' decreased by 50% (8 cm/sec), late diastolic A' increased by 45%, and systolic S' remains unchanged. TDI of the RV free wall approximately 8 beats after the Braslet was released shows early diastolic E' (8 cm/sec), late diastolic A' (12 cm/sec), and systolic S' (13 cm/sec) velocities. During this portion of the release, early diastolic E' did not recover to baseline values but late diastolic A' and systolic S' recovered to pre-Braslet values. The pre-systolic cross-sectional area of the internal jugular vein with Braslet off was 1.07 cm(sup 2) and 1.13 cm(sup 2) 10 min after the Braslet was applied. The presystolic cross-sectional area of the common femoral vein with Braslet off was 0.50 cm(sup 2), and was 0.54 cm(sup 2) 10 min after the Braslet was applied. The right ventricular myocardial performance Tei index also was calculated for comparison with typical values found in healthy subjects on Earth. Baseline and Braslet-on values for Tei index were 0.25 and 0.22 respectively. Braslet Tei indices are within normal ranges found in healthy subjects and temporarily become greater than 0.4 during the dynamic Braslet release portion of this study. Tissue Doppler imaging of the right ventricle revealed that the Braslet influenced cardiac preload and that fluid was sequestered in the lower-extremity interstitial and vascular space after only 10 minutes of application. This report demonstrates that Braslet application affects right ventricular physiology in long-duration space flight based on TDI and that this effect is in part due to venous hemodynamics.

  1. Chemotherapy of Rodent Malaria Evaluation of Drug Action Against Normal and Resistant Strains, Including Exo-Erythrocytic Stages

    DTIC Science & Technology

    1976-12-01

    RESISTANCEI (U) CHLOROQUINE 20. iXDsrRAcT (Contrate a reverse atide ft nwce~saty and Identify by block number) Data are provided on the blood schizontocidal...litl meffeoqne uptake ofadequoine. TL synergistic action of chloroquine and erythromycin against chioroquine-resistant parasites has benfurther...Causal prophylaxis - the value of the rodent screen 3 4.3 Sustained release of drugs 4 4.4 Mode of drug action 5 4.4.1 Chloroquine and mefloquine 5

  2. Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

    PubMed

    Warren, W B; Gurewitsch, E D; Goland, R S

    1995-02-01

    We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

  3. ATP release from bladder urothelium and serosa in a rat model of partial bladder outlet obstruction.

    PubMed

    Shiina, Kazuhiro; Hayashida, Ken-Ichiro; Ishikawa, Kazuo; Kawatani, Masahito

    2016-01-01

    Overactive bladder is one of the major health problem especially in elderly people. Adenosine triphosphate (ATP) is released from urinary bladder cells and acts as a smooth muscle contraction and sensory signal in micturition but little is known about the role of ATP release in the pathophysiology of overactive bladder. To assess the relationship between ATP and overactive bladder, we used a partial bladder outlet obstruction (pBOO) model in rats. The bladder caused several changes by pBOO: An increase in bladder weight, hypertrophy of sub-urothelium and sub-serosal area, and frequent non-voiding bladder contraction during urine storage. Basal ATP release from urothelium and serosa of pBOO rats was significantly higher than that of normal rats. Distentioninduced ATP release from urothelium of normal and pBOO rats had no significant change. However, distention-induced ATP release from serosa of pBOO rats was higher than that of normal. These findings may identify ATP especially released from serosa as one of causes of non-voiding contractions and overactive bladder symptoms.

  4. Micropuncture studies of the recovery phase of myohemoglobinuric acute renal failure in the rat

    PubMed Central

    Oken, Donald E.; DiBona, Gerald F.; McDonald, Franklin D.

    1970-01-01

    Micropuncture studies of the recovery phase of glycerol-induced myohemoglobinuric acute renal failure were performed in rats whose blood urea nitrogen (BUN) had fallen at least 20% below its peak value. The glomerular filtration rate (GFR) of individual nephrons in a single kidney in the recovery period generally either was in the normal range or minimal. Each animal's BUN concentration at the time of the study was inversely related to the proportion of functioning surface nephrons, but did not correlate with individual nephron GFR values. Proximal tubule fractional water absorption was significantly depressed as manifested by both depressed inulin (TF/P) values and supernormal volumes of collections, a finding which, in the absence of a urea-induced osmotic diuresis, suggests impaired sodium transport by the damaged nephron. The mean proximal tubule hydrostatic pressure in recovery was normal and there was little variation in pressure among functioning nephrons. It is concluded that recovery from this model of acute renal failure reflects the progressive recruitment of increasing numbers of functioning nephrons. The recovery of individual nephron glomerular filtration, once begun, was rapid and complete. No evidence could be adduced that the gradual return of renal function towards normal reflects a slow release of tubular obstruction or repair of disrupted tubular epithelium. Rather, recovery appeared to be directly attributable to the return of an adequate effective glomerular filtration pressure. Significant limitation in proximal tubule water absorption persisted after individual nephron GFR had returned to normal or supernormal values in this model of experimental acute renal failure in the rat, a finding which readily accounts for the diuresis associated with the recovery phase of this syndrome. PMID:5443173

  5. Exact solution of two collinear cracks normal to the boundaries of a 1D layered hexagonal piezoelectric quasicrystal

    NASA Astrophysics Data System (ADS)

    Zhou, Y.-B.; Li, X.-F.

    2018-07-01

    The electroelastic problem related to two collinear cracks of equal length and normal to the boundaries of a one-dimensional hexagonal piezoelectric quasicrystal layer is analysed. By using the finite Fourier transform, a mixed boundary value problem is solved when antiplane mechanical loading and inplane electric loading are applied. The problem is reduce to triple series equations, which are then transformed to a singular integral equation. For uniform remote loading, an exact solution is obtained in closed form, and explicit expressions for the electroelastic field are determined. The intensity factors of the electroelastic field and the energy release rate at the inner and outer crack tips are given and presented graphically.

  6. Essays in environmental economics

    NASA Astrophysics Data System (ADS)

    Bartz-Marvez, Sherry L.

    This body of work contributes to the literature on two current topics in environmental economics: (1) the relationship between economic development and environmental degradation; and (2) the effectiveness of mandatory information disclosure as a regulatory instrument. For the first topic, we link theoretical and empirical Environmental Kuznets Curve research by using calibration and simulation to test a growth model with environmental quality as a normal good and emissions as a factor of production. We use U.S. macroeconomic, emissions and compliance data to calibrate parameters representing preferences for environmental quality and marginal abatement costs. We simulate the model starting from a less-developed initial condition and compare the predicted pollution-income relationship with that in the data. Our results are mixed. Some support exists for the theory that an inverted U-shape results from a corner solution in which less developed countries do not abate pollution. However, pollution peaks at a level of per capita income which is much lower than that observed in the U.S. data. For the second topic, we study the effectiveness of mandatory information disclosure as environmental regulation. Community-right-to-know programs such as the EPA's Toxic Release Inventory (TRI) use mandatory information disclosure to "shame" dirty firms into reducing emissions. The idea is that the public---armed with previously unavailable emissions information---will pressure firms with higher-than-expected emissions to "clean-up." We use the electricity industry to study the impact of price-and-entry deregulation on the effectiveness of the TRI. Using event studies, we find that, on average, utilities experience losses in firm value immediately following TRI announcements. Using panel regressions, we show that toxic emissions released in regulated states are associated with decreases in firm value while those released in deregulated states are associated with increases in firm value. We then estimate the impact of changes in firm value on subsequent emissions, finding that releases of most TRI pollutants are reduced in regulated states, but not in deregulated states.

  7. Effects of storage temperature and time of antimony release from PET bottles into drinking water in China.

    PubMed

    Qiao, Fei; Lei, Kun; Li, Zicheng; Liu, Qing; Wei, Zhanliang; An, Lihui; Qi, Hongli; Cui, Song

    2018-01-01

    Antimony (Sb) concentrations were measured in 10 brands of PET bottled drinking water available in supermarkets in China. To simulate general storage habits based on market research, these PET bottles with drinking water were stored for 4 weeks in a lab or a car trunk during the summer. Although the PET package material of brand A had the lowest Sb level (142.71 ± 29.81 μg/g), it showed a significant increase in Sb concentrations when stored in both the car trunk and the lab. There was significant release of Sb from the PET bottles into the water following 24 h of incubation at ≥ 40 °C (40, 50, 60, and 70 °C), especially at 70 °C. The potential health risk of Sb release from PET bottles was calculated based on daily intake values and determined to be acceptable for consumers under normal storage conditions.

  8. Acute effects of clonidine and growth-hormone-releasing hormone on growth hormone secretion in patients with hyperthyroidism.

    PubMed

    Giustina, A; Buffoli, M G; Bussi, A R; Wehrenberg, W B

    1991-01-01

    Patients with hyperthyroidism have reduced growth hormone (GH) responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of clonidine on GH secretion has been suggested to depend on an enhancement of hypothalamic GH-releasing hormone (GHRH) release. The aim of our study was to evaluate the effects of clonidine and GHRH on GH secretion in patients with hyperthyroidism. Eight hyperthyroid females with recent diagnosis of Graves' disease (age range 20-55 years, body mass index range 19.2-26.2 kg/m2) and 6 healthy female volunteers (age range 22-35 years, body mass index range 19-25 kg/m2) underwent two experimental trials at no less than 7-day intervals: (a) an intravenous infusion of clonidine 150 micrograms in 10 ml of saline, or (b) a bolus intravenous injection of human GHRH (1-29)NH2, 100 micrograms in 1 ml of saline. Hyperthyroid patients showed blunted GH peaks after clonidine (7.1 +/- 1.7 micrograms/l) as compared to normal subjects receiving clonidine (28.5 +/- 4.9 micrograms/l, p less than 0.05). GH peaks after GHRH were also significantly lower in hyperthyroid subjects (8.0 +/- 1.7 micrograms/l) as compared to normal subjects receiving GHRH (27.5 +/- 4.4 micrograms/l, p less than 0.05). No significant differences in the GH values either after clonidine or GHRH were observed in the two groups of subjects examined. Our data demonstrate that the GH responses to clonidine as well as to GHRH in patients with hyperthyroidism are inhibited in a similar fashion with respect to normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Stable Isotope Systematics of Martian Perchlorate

    NASA Astrophysics Data System (ADS)

    Martin, P.; Farley, K. A.; Archer, D., Jr.; Atreya, S. K.; Conrad, P. G.; Eigenbrode, J. L.; Fairen, A.; Franz, H. B.; Freissinet, C.; Glavin, D. P.; Mahaffy, P. R.; Malespin, C.; Ming, D. W.; Navarro-Gonzalez, R.; Sutter, B.

    2015-12-01

    Chlorine isotopic compositions in HCl released during evolved gas analysis (EGA) runs have been detected by the Sample Analysis at Mars (SAM) instrument on the Curiosity rover ranging from approximately -9‰ to -50‰ δ37Cl, with two spatially and isotopically separated groups of samples averaging -15‰ and -45‰. These extremely low values are the first such detection of any known natural material; common terrestrial values very rarely exceed ±5‰, and the most extreme isotopic signature yet detected elsewhere in the solar system are values of around +24‰ on the Moon. The only other known location in the solar system with large negative chlorine isotopes is the Atacama Desert, where perchlorate with -14‰ δ37Cl has been detected. The Atacama perchlorate has unusual Δ17O signatures associated with it, indicating a formation mechanism involving O3, which suggests an atmospheric origin of the perchlorate and associated large isotopic anomalies. Identification of non-zero positive Δ17O signatures in the O2 released during EGA runs would allow definitive evidence for a similar process having occurred on Mars. Perchlorate is thought to be the most likely source of HCl in EGA runs due to the simultaneous onset of O2 release. If perchlorate is indeed the HCl source, atmospheric chemistry could be responsible for the observed isotopic anomalies, with variable extents of perchlorate production producing the isotopic variability. However, chloride salts have also been observed to release HCl upon heating; if the timing of O2 release is merely coincidental, observed HCl could be coming from chlorides. At thermodynamic equilibrium, the fractionation factor of perchlorate reduction is 0.93, meaning that differing amounts of post-deposition reduction of isotopically normal perchlorate to chloride could account for the highly variable Cl isotopes. Additionally, post-deposition reduction could account for the difference between the two Cl isotopic groups if perchlorate is the HCl source, as the residual perchlorate after reduction will be isotopically heavy. Therefore, conclusive determination of the origin of HCl released during EGA is vital to understanding the origin of this large δ37Cl anomaly.

  10. Serum LH and FSH Responses to Synthetic LH-RH in Normal Infants, Children and Patients With Turner's Syndrome

    ERIC Educational Resources Information Center

    Suwa, Seizo; And Others

    1974-01-01

    Effects of luteinizing hormone-releasing hormone (LH-RH) on LH and follicle-stimulating hormone (FSH) release were studied in 26 normal children and six patients (from 1-to 14-years-old) with Turner's syndrome. (Author)

  11. Altered neuroendocrine regulation of gonadotropin secretion in women distance runners.

    PubMed

    Veldhuis, J D; Evans, W S; Demers, L M; Thorner, M O; Wakat, D; Rogol, A D

    1985-09-01

    We tested the hypothesis that the neuroendocrine control of gonadotropin secretion is altered in certain women distance runners with secondary amenorrhea. To this end, we quantitated the frequency and amplitude of spontaneous pulsatile LH secretion during a 24-h interval in nine such women. The ability of the pituitary gland to release LH normally was assessed by administration of graded bolus doses of GnRH during the subsequent 8 h. Compared to normally menstruating women, six of nine amenorrheic distance runners had a distinct reduction in spontaneous LH pulse frequency, with one, three, six, five, four, or two pulses per 24 h (normal, 8-15 pulses/24 h). This reduction in LH pulse frequency occurred without any significant alterations in plasma concentrations of estradiol and free testosterone or 24-h integrated serum concentrations of LH, FSH, or PRL. Moreover, in long-distance runners, the capacity of the pituitary gland to release LH was normal or accentuated in response to exogenous pulses of GnRH. In the six women athletes with diminished spontaneous LH pulsatility, acute ovarian responsiveness also was normal, since serum estradiol concentrations increased normally in response to the GnRH-induced LH pulses. Although long-distance runners had significantly lower estimated percent body fat compared to control women, specific changes in pulsatile gonadotropin release did not correlate with degree of body leanness. In summary, certain long-distance runners with secondary amenorrhea or severe oligomenorrhea have unambiguously decreased spontaneous LH pulse frequency with intact pituitary responsiveness to GnRH. This neuroendocrine disturbance may be relevant to exercise-associated amenorrhea, since pulsatile LH release is a prerequisite for cyclic ovarian function. We speculate that such alterations in pulsatile LH release in exercising women reflect an adaptive response of the hypothalamic pulse generator controlling the intermittent GnRH signal to the pituitary gland. The basis for amenorrhea in the remaining runners who have normal pulsatile properties of LH release is not known.

  12. Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen-independent prostate cancer patients.

    PubMed

    Yashi, Masahiro; Muraishi, Osamu; Kobayashi, Yutaka; Tokue, Akihiko; Nanjo, Hiroshi

    2002-05-01

    Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor. In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects. We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen-independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA. The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone. Copyright 2002 Wiley-Liss, Inc.

  13. Variability in platelet dense granule adenosine triphosphate release findings amongst patients tested multiple times as part of an assessment for a bleeding disorder.

    PubMed

    Badin, M S; Graf, L; Iyer, J K; Moffat, K A; Seecharan, J L; Hayward, C P M

    2016-12-01

    Lumi-aggregometry quantification of platelet dense granule adenosine triphosphate (ATP) release is commonly used for diagnosing platelet function disorders. As the test findings show considerable variability for healthy controls, we postulated that patient findings might also be variable and investigated patients who were assessed for dense granule ATP release defects more than once. Analyses were performed on prospectively collected data for first and second tests for subjects tested for dense granule ATP release defects more than once by the Hamilton Regional Laboratory Program (HRLMP) between January 2007 and June 2013 (cohort I). Similar analyses were performed for subjects who were recruited to a platelet disorder study (cohort II) and were assessed for ATP release defects more than once before October 2015. A total of 150 unique subjects had multiple ATP release tests. Results with individual agonists were variable for many subjects. While normal findings with all tested agonists were often confirmed by the second test (cohort I: 83%; cohort II: 100%), impaired release with multiple agonists was confirmed in only some subjects (cohort I: 34%; cohort II: 54%). Inconsistent findings were common (cohort I: 36%; cohort II: 39%). ISTH bleeding scores showed no relationship to the test findings. The finding of impaired ATP release with 2 or more agonists on both tests was not associated with an increased likelihood of a definite bleeding disorder. The variability in platelet dense granule ATP release findings amongst patients assessed for diagnostic purposes suggests that the test has limited value for diagnosing platelet disorders. © 2016 John Wiley & Sons Ltd.

  14. Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar

    PubMed Central

    Domingos, Ana I; Sordillo, Aylesse; Dietrich, Marcelo O; Liu, Zhong-Wu; Tellez, Luis A; Vaynshteyn, Jake; Ferreira, Jozelia G; Ekstrand, Mats I; Horvath, Tamas L; de Araujo, Ivan E; Friedman, Jeffrey M

    2013-01-01

    Sugars that contain glucose, such as sucrose, are generally preferred to artificial sweeteners owing to their post-ingestive rewarding effect, which elevates striatal dopamine (DA) release. While the post-ingestive rewarding effect, which artificial sweeteners do not have, signals the nutrient value of sugar and influences food preference, the neural circuitry that mediates the rewarding effect of glucose is unknown. In this study, we show that optogenetic activation of melanin-concentrating hormone (MCH) neurons during intake of the artificial sweetener sucralose increases striatal dopamine levels and inverts the normal preference for sucrose vs sucralose. Conversely, animals with ablation of MCH neurons no longer prefer sucrose to sucralose and show reduced striatal DA release upon sucrose ingestion. We further show that MCH neurons project to reward areas and are required for the post-ingestive rewarding effect of sucrose in sweet-blind Trpm5−/− mice. These studies identify an essential component of the neural pathways linking nutrient sensing and food reward. DOI: http://dx.doi.org/10.7554/eLife.01462.001 PMID:24381247

  15. Formulation, Characterization and Stability Assessment of a Food-Derived Tripeptide, Leucine-Lysine-Proline Loaded Chitosan Nanoparticles.

    PubMed

    Danish, Minna K; Vozza, Giuliana; Byrne, Hugh J; Frias, Jesus M; Ryan, Sinéad M

    2017-09-01

    The chicken- or fish-derived tripeptide, leucine-lysine-proline (LKP), inhibits the angiotensin converting enzyme and may be used as an alternative treatment for prehypertension. However, it has low permeation across the small intestine. The formulation of LKP into a nanoparticle (NP) has the potential to address this issue. LKP-loaded NPs were produced using an ionotropic gelation technique, using chitosan (CL113). Following optimization of unloaded NPs, a mixture amount design was constructed using variable concentration of CL113 and tripolyphosphate at a fixed LKP concentration. Resultant particle sizes ranged from 120 to 271 nm, zeta potential values from 29 to 37 mV, and polydispersity values from 0.3 to 0.6. A ratio of 6:1 (CL113:TPP) produced the best encapsulation of approximately 65%. Accelerated studies of the loaded NPs indicated stability under normal storage conditions (room temperature). Cytotoxicity assessment showed no significant loss of cell viability and in vitro release studies indicated an initial burst followed by a slower and sustained release. © 2017 Institute of Food Technologists®.

  16. Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5mg intravaginal prasterone for 12 weeks.

    PubMed

    Martel, Céline; Labrie, Fernand; Archer, David F; Ke, Yuyong; Gonthier, Renaud; Simard, Jean-Nicolas; Lavoie, Lyne; Vaillancourt, Mario; Montesino, Marlene; Balser, John; Moyneur, Érick

    2016-05-01

    This study integrates all data obtained in women aged 40-80years enrolled with moderate to severe symptoms of vulvovaginal atrophy (VVA) who received daily intravaginal administration of 0.50% (6.5mg) dehydroepiandrosterone (DHEA; prasterone) for 12weeks (n=723; ITT-S population) as compared with placebo (n=266; ITT-S population). To this end, serum steroid levels (DHEA, DHEA-sulfate (DHEA-S), androst-5-ene-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G)) were measured at Day 1 and Week 12 by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following validation performed according to the FDA guidelines [1-6]. In agreement with the mechanisms of intracrinology where DHEA is exclusively transformed intracellularly into active sex steroids which act and are inactivated locally before being released as glucuronided or sulfated metabolites for elimination by the kidneys and liver, all sex steroids remained well within normal postmenopausal values following administration of intravaginal DHEA. Serum estradiol, the most relevant sex steroid, was measured after 12weeks of treatment at 3.36pg/ml (cITT-S population) or 19% below the normal postmenopausal value of 4.17pg/ml. On the other hand, serum E1-S, the best recognized marker of global estrogenic activity, shows an average value of 209pg/ml at 12 weeks compared to 220pg/ml in normal postmenopausal women. Moreover, serum ADT-G, the main metabolite of androgens, also remains well within normal postmenopausal values. The present data shows that a low daily intravaginal dose (6.5mg) of DHEA (prasterone) which is efficacious on the symptoms and signs of VVA, permits to achieve the desired local efficacy without systemic exposure, in agreement with the stringent mechanisms of menopause established after 500 million years of evolution where each cell in each tissue is the master of its sex steroid exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Interaction between protein kinase C and protein kinase A can modulate transmitter release at the rat neuromuscular synapse.

    PubMed

    Santafé, M M; Garcia, N; Lanuza, M A; Tomàs, M; Tomàs, J

    2009-02-15

    We used intracellular recording to investigate the functional interaction between protein kinase C (PKC) and protein kinase A (PKA) signal transduction cascades in the control of transmitter release in the neuromuscular synapses from adult rats. Our results indicate that: 1) PKA and PKC are independently involved in asynchronous release. 2) Evoked acetylcholine (ACh) release is enhanced with the PKA agonist Sp-8-BrcAMP and the PKC agonist phorbol ester (PMA). 3) PKA has a constitutive role in promoting a component of normal evoked transmitter release because, when the kinase is inhibited with H-89, the release diminishes. However, the PKC inhibitor calphostin C (CaC) does not affect ACh release. 4) PKA regulates neurotransmission without PKC involvement because, after PMA or CaC modulation of the PKC activity, coupling to the ACh release of PKA can normally be stimulated with Sp-8-BrcAMP or inhibited with H-89. 5) After PKA inhibition with H-89, PKC stimulation with PMA (or inhibition with CaC) does not lead to any change in evoked ACh release. However, in PKA-stimulated preparations with Sp-8-BrcAMP, PKC becomes tonically active, thus potentiating a component of release that can now be blocked with CaC. In normal conditions, therefore, PKA was able to modulate ACh release independently of PKC activity, whereas PKA stimulation caused the PKC coupling to evoked release. In contrast, PKA inhibition prevent PKC stimulation (with the phorbol ester) and coupling to ACh output. There was therefore some dependence of PKC on PKA activity in the fine control of the neuromuscular synaptic functionalism and ACh release.

  18. Historical Doses from Tritiated Water and Tritiated Hydrogen Gas Released to the Atmosphere from Lawrence Livermore National Laboratory (LLNL). Part 5. Accidental Releases

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

    Peterson, S

    2007-08-15

    Over the course of fifty-three years, LLNL had six acute releases of tritiated hydrogen gas (HT) and one acute release of tritiated water vapor (HTO) that were too large relative to the annual releases to be included as part of the annual releases from normal operations detailed in Parts 3 and 4 of the Tritium Dose Reconstruction (TDR). Sandia National Laboratories/California (SNL/CA) had one such release of HT and one of HTO. Doses to the maximally exposed individual (MEI) for these accidents have been modeled using an equation derived from the time-dependent tritium model, UFOTRI, and parameter values based onmore » expert judgment. All of these acute releases are described in this report. Doses that could not have been exceeded from the large HT releases of 1965 and 1970 were calculated to be 43 {micro}Sv (4.3 mrem) and 120 {micro}Sv (12 mrem) to an adult, respectively. Two published sets of dose predictions for the accidental HT release in 1970 are compared with the dose predictions of this TDR. The highest predicted dose was for an acute release of HTO in 1954. For this release, the dose that could not have been exceeded was estimated to have been 2 mSv (200 mrem), although, because of the high uncertainty about the predictions, the likely dose may have been as low as 360 {micro}Sv (36 mrem) or less. The estimated maximum exposures from the accidental releases were such that no adverse health effects would be expected. Appendix A lists all accidents and large routine puff releases that have occurred at LLNL and SNL/CA between 1953 and 2005. Appendix B describes the processes unique to tritium that must be modeled after an acute release, some of the time-dependent tritium models being used today, and the results of tests of these models.« less

  19. Computational study of a calcium release-activated calcium channel

    NASA Astrophysics Data System (ADS)

    Talukdar, Keka; Shantappa, Anil

    2016-05-01

    The naturally occurring proteins that form hole in membrane are commonly known as ion channels. They play multiple roles in many important biological processes. Deletion or alteration of these channels often leads to serious problems in the physiological processes as it controls the flow of ions through it. The proper maintenance of the flow of ions, in turn, is required for normal health. Here we have investigated the behavior of a calcium release-activated calcium ion channel with pdb entry 4HKR in Drosophila Melanogaster. The equilibrium energy as well as molecular dynamics simulation is performed first. The protein is subjected to molecular dynamics simulation to find their energy minimized value. Simulation of the protein in the environment of water and ions has given us important results too. The solvation energy is also found using Charmm potential.

  20. Antioxidant treatment prevents the development of fructose-induced abdominal adipose tissue dysfunction.

    PubMed

    Fariña, Juan Pablo; García, María Elisa; Alzamendi, Ana; Giovambattista, Andrés; Marra, Carlos Alberto; Spinedi, Eduardo; Gagliardino, Juan José

    2013-07-01

    In the present study, we tested the effect of OS (oxidative stress) inhibition in rats fed on an FRD [fructose-rich diet; 10% (w/v) in drinking water] for 3 weeks. Normal adult male rats received a standard CD (commercial diet) or an FRD without or with an inhibitor of NADPH oxidase, APO (apocynin; 5 mM in drinking water; CD-APO and FRD-APO). We thereafter measured plasma OS and metabolic-endocrine markers, AAT (abdominal adipose tissue) mass and cell size, FA (fatty acid) composition (content and release), OS status, LEP (leptin) and IRS (insulin receptor substrate)-1/IRS-2 mRNAs, ROS (reactive oxygen species) production, NADPH oxidase activity and LEP release by isolated AAT adipocytes. FRD-fed rats had larger AAT mass without changes in body weight, and higher plasma levels of TAG (triacylglycerol), FAs, TBARS (thiobarbituric acid-reactive substance) and LEP. Although no significant changes in glucose and insulin plasma levels were observed in these animals, their HOMA-IR (homoeostasis model assessment of insulin resistance) values were significantly higher than those of CD. The AAT from FRD-fed rats had larger adipocytes, higher saturated FA content, higher NADPH oxidase activity, greater ROS production, a distorted FA content/release pattern, lower insulin sensitivity together with higher and lower mRNA content of LEP and IRS-1-/2 respectively, and released a larger amount of LEP. The development of all the clinical, OS, metabolic, endocrine and molecular changes induced by the FRD were significantly prevented by APO co-administration. The fact that APO treatment prevented both changes in NADPH oxidase activity and the development of all the FRD-induced AAT dysfunctions in normal rats strongly suggests that OS plays an important role in the FRD-induced MS (metabolic syndrome) phenotype.

  1. Development of pituitary adenoma in women with hyperprolactinaemia: clinical, endocrine, and radiological characteristics.

    PubMed Central

    Pontiroli, A E; Falsetti, L

    1984-01-01

    Sixty eight women referred for treatment of hyperprolactinaemia entered a three year follow up study to determine the clinical and endocrine course of the disease and its association with microadenoma of the pituitary. Details recorded before treatment included medical history, gonadotrophin and ovarian hormonal concentrations, and release of prolactin in response to protirelin (thyrotrophin releasing hormone), benserazide, cimetidine, and nomifensine. Sellar tomography was then performed yearly for three years in all women, 54 of them also undergoing computed coronal and sagittal tomography. At baseline evaluation 27 women showed radiological evidence of pituitary adenoma; at the end of the follow up period the number had increased to 41. Amenorrhoea, steady and raised serum prolactin concentrations, a low ratio of luteinising hormone to follicle stimulating hormone, a longer duration of disease, and low serum progesterone concentrations were more common in women with a final diagnosis of pituitary adenoma than in those whose sella remained normal. Tests for release of prolactin had yielded abnormal results from the outset in all 41 women with radiological evidence of pituitary adenoma and in about half of those whose sella had remained radiologically normal. Response to medical treatment (metergoline in 20 patients, bromocriptine in 21) was similar and showed no difference between patients with tumorous and non-tumorous hyperprolactinaemia. These findings suggest that a large proportion of women with hyperprolactinaemia may harbour a prolactin secreting pituitary adenoma which becomes apparent over a relatively short period. Amenorrhoea and steady and raised serum prolactin concentrations are more common in these women. Tests for release of prolactin are of predictive value in identifying women who will develop a pituitary adenoma. PMID:6421360

  2. Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria.

    PubMed Central

    Sandberg, S; Brun, A

    1982-01-01

    The photohemolysis of normal erythrocytes incubated with protoporphyrin is reduced in the presence of albumin. When globin is added to normal erythrocytes loaded with protoporphyrin, protoporphyrin is bound to globin. During irradiation protoporphyrin moves from globin to the erythrocyte membrane and photohemolysis is initiated. Erythrocytes in patients with erythropoietic protoporphyria contain large amounts of protoporphyrin bound to hemoglobin. Upon irradiation of these cells in the absence of albumin, 40% of protoporphyrin and 80% of hemoglobin is released after 240 kJ/m2. The released protoporphyrin is hemoglobin bound. In contrast, when albumin is present only 8% of hemoglobin is released whereas protoporphyrin is released to 76%. The released protoporphyrin is albumin bound. A hypothesis for the release of erythrocyte protoporphyrin in erythropoietic protoporphyria without simultaneous hemolysis is proposed. Upon irradiation protoporphyrin photodamages its binding sites on hemoglobin, moves through the plasma membrane, and is bound to albumin in plasma. PMID:7107898

  3. Zero gravity and cardiovascular homeostasis. The relationship between endogenous hyperprolactinemia and plasma aldosterone

    NASA Technical Reports Server (NTRS)

    Haber, E.; Re, R. N.; Kourides, I. A.; Weihl, A. C.; Maloof, F.

    1978-01-01

    Prolactin, thyrotropin and aldosterone were measured by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in normal women before and after the intravenous injection of 200 micrograms of thyrotropin releasing hormone. Prolactin increased at 15 minutes following thyrotropin releasing hormone. Plasma renin activity was not different from control levels during the first hour following the administration of thyrotropin releasing hormone, nor did the plasma aldosterone concentration differ significantly from the control levels during this period. However, with upright posture, an increase in aldosterone and in plasma renin activity was noted, demonstrating a normal capacity to secrete aldosterone. Similarly, no change in aldosterone was seen in 9 patients with primary hypothyroidism given thyrotropin releasing hormone, despite the fact that the increase in prolactin was greater than normal. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

  4. 49 CFR 236.791 - Release, value.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Release, value. 236.791 Section 236.791 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Release, value. The electrical value at which the movable member of an electromagnetic device will move to...

  5. Effects of molgramostim, filgrastim and lenograstim in the treatment of myelokathexis.

    PubMed

    Černelč, Peter; Andoljšek, Dušan; Mlakar, Uroš; Pretnar, Jože; Modic, Mojca; Zupan, Irena P; Zver, Samo

    2000-01-01

    Myelokathexis is a very rare form of chronic hereditary neutropenia resulting from impaired neutrophil releasing mechanism in the bone marrow. The recombinant human granulocyte-macrophage (molgramostim) and granulocyte (filgrastim, lenograstim) colony stimulating factors release the mature granulocytes from the bone marrow. We describe a 43-year-old woman suffering from myelokathexis, with the absolute neutrophil count ranging between 0.03 and 1.35 × 10 9 /L. In the period before the introduction of cytokines, the patient had more than 80 major infectious episodes. Since 1991, infections in this patient have been treated with cytokines, given in conjunction with antibiotics. Initially, she received molgramostim in a daily dose of 5 μg/kg subcutaneously, which stimulated the release of granulocytes from her bone marrow, thereby allowing successful treatment of infection. After the development of hypersensitivity, molgramostim was substituted with filgrastim. Finally, lenograstim was given a trial. With all three cytokines, the patient's neutrophil count always attained normal values already 4 hours after subcutaneous application of the drug in a dose of 5 μg/kg, the highest neutrophil levels were measured at 24 hours post-injection, and the neutrophil count was again close to the baseline value 72 hours after the treatment. A slight neutropenia was present 48 hours after the application of filgrastim. We believe that all three cytokines are equally effective in increasing the neutrophil count in venous blood of patients with myelokathexis.

  6. Platelet von Willebrand factor in Hermansky-Pudlak syndrome.

    PubMed

    McKeown, L P; Hansmann, K E; Wilson, O; Gahl, W; Gralnick, H R; Rosenfeld, K E; Rosenfeld, S J; Horne, M K; Rick, M E

    1998-10-01

    The Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment, and a mild to moderate bleeding diathesis attributed to storage-pool deficient (SPD) platlets. Patients have platelet aggregation and release abnormalities. In addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS patients have been associated with a greater bleeding tendency than would be predicted from either condition alone. Other HPS patients have severe bleeding despite normal levels of plasma vWF, suggesting that at least one additional factor is responsible for their bleeding diathesis. Because platelet vWF levels have been well correlated with clinical bleeding times in patients with von Willebrand's disease, we have measured the platelet vWF activity and antigen levels in 30 HPS patients and have attempted to correlate their clinical bleeding with these values. The platelet vWF activity levels in patients was significantly lower than that of normal subjects (P < 0.0001). The patients as a group also had slightly lower values of plasma vWF activity when compared with normals (P-0.03). In 11 of the HPS patients, the multimeric structure of plasma vWF showed a decrease in the high molecular weight multimers and an increase in the low molecular weight multimers. In correlating the platelet and plasma vWF values with the bleeding histories, we were not able to show a predictable relationship in the majority of the patients.

  7. Control of lipopolysaccharide biosynthesis and release by Escherichia coli and Salmonella typhimurium.

    PubMed Central

    Ishiguro, E E; Vanderwel, D; Kusser, W

    1986-01-01

    The influence of the relA gene on lipopolysaccharide (LPS) biosynthesis and release by Escherichia coli and Salmonella typhimurium was investigated. Similar results were obtained with both species. The incorporation of [3H]galactose into LPS by galE mutants was inhibited by at least 50% (as compared with normal growing controls) during amino acid deprivation of relA+ strains. This inhibition could be prevented by the treatment of the amino acid-deprived relA+ bacteria with chloramphenicol, a known antagonist of the stringent control mechanism. Furthermore, LPS biosynthesis was not inhibited during amino acid deprivation of isogenic relA mutant strains. These results indicate that LPS synthesis is regulated by the stringent control mechanism. Normal growing cells of both relA+ and relA strains released LPS into the culture fluid at low rates. Amino acid deprivation stimulated the rate of LPS release by relA mutants but not by relA+ bacteria. Chloramphenicol treatment markedly stimulated the release of cell-bound LPS by amino acid-deprived relA+ cells. Thus, a low rate of LPS release was characteristic of normal growth and could be increased in nongrowing cells by relaxing the control of LPS synthesis. Images PMID:3531174

  8. Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin-like growth factor II-like peptide.

    PubMed

    Boari, A; Barreca, A; Bestetti, G E; Minuto, F; Venturoli, M

    1995-06-01

    A 12-year-old mixed-breed male dog was referred to the Clinica Medica Veterinaria of Bologna University for recurrent episodes of seizures due to hypoglycemia with abnormally low plasma insulin levels (18 pmol/l). Resection of a large leiomyoma (780 g) of the gastric wall resulted in a permanent resolution of the hypoglycemic episodes. Insulin-like growth factors I and II (IGF-I and -II) were measured by RIA in serum before and after surgery and in tumor tissue. Results were compared to the serum concentration of 54 normal and to the tissue concentration observed in eight non-hypoglycemic dog gastric wall extracts. Before surgery, circulating immunoreactive IGF-I was 0.92 nmol/l, which is significantly lower than the control values (16.92 +/- 8.44 nmol/l, range 3.53-35.03), while IGF-II was 152 nmol/l, which is significantly higher than the control values (42.21 +/- 3.75, range 31.99-50.74). After surgery, IGF-I increased to 6.80 nmol/l while IGF-II decreased to 45.52 nmol/l. Tumor tissue IGF-II concentration was higher than normal (5.66 nmol/kg tissue as compared to a range in normal gastric wall tissue of 1.14-3.72 nmol/kg), while IGF-I was 0.08 nmol/kg tissue, which is close to the lowest normal value (range in controls, 0.08-1.18 nmol/kg). Partial characterization of IGF-II immunoreactivity extracted from tissue evidenced a molecular weight similar to that of mature IGF-II, thus excluding that peptide released by the tumor is a precursor molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Characterization of crack growth under combined loading

    NASA Technical Reports Server (NTRS)

    Feldman, A.; Smith, F. W.; Holston, A., Jr.

    1977-01-01

    Room-temperature static and cyclic tests were made on 21 aluminum plates in the shape of a 91.4x91.4-cm Maltese cross with 45 deg flaws to develop crack growth and fracture toughness data under mixed-mode conditions. During cyclic testing, it was impossible to maintain a high proportion of shear-mode deformation on the crack tips. Cracks either branched or turned. Under static loading, cracks remained straight if shear stress intensity exceeded normal stress intensity. Mixed-mode crack growth rate data compared reasonably well with published single-mode data, and measured crack displacements agreed with the straight and branched crack analyses. Values of critical strain energy release rate at fracture for pure shear were approximately 50% higher than for pure normal opening, and there was a large reduction in normal stress intensity at fracture in the presence of high shear stress intensity. Net section stresses were well into the inelastic range when fracture occurred under high shear on the cracks.

  10. Development of Spatial Release from Masking in Mandarin-Speaking Children with Normal Hearing

    ERIC Educational Resources Information Center

    Yuen, Kevin C. P.; Yuan, Meng

    2014-01-01

    Purpose: This study investigated the development of spatial release from masking in children using closed-set Mandarin disyllabic words and monosyllabic words carrying lexical tones as test stimuli and speech spectrum-weighted noise as a masker. Method: Twenty-six children ages 4-9 years and 12 adults, all with normal hearing, participated in…

  11. Short-term visual deprivation can enhance spatial release from masking.

    PubMed

    Pagé, Sara; Sharp, Andréanne; Landry, Simon P; Champoux, François

    2016-08-15

    This research aims to study the effect of short-term visual deprivation on spatial release from masking, a major component of the cocktail party effect that allows people to detect an auditory target in noise. The Masking Level Difference (MLD) test was administered on healthy individuals over three sessions: before (I) and after 90min of visual deprivation (II), and after 90min of re-exposure to light (III). A non-deprived control group performed the same tests, but remained sighted between sessions I and II. The non-deprived control group displayed constant results across sessions. However, performance in the MLD test was improved following short-term visual deprivation and performance returned to pre-deprivation values after light re-exposure. This study finds that short-term visual deprivation transiently enhances the spatial release from masking. These data suggest the significant potential for enhancing a process involved in the cocktail party effect in normally developing individuals and adds to an emerging literature on the potential to enhance auditory ability after only a brief period of visual deprivation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Purity of food cooked in stainless steel utensils.

    PubMed

    Flint, G N; Packirisamy, S

    1997-01-01

    An extensive programme of cooking operations, using household recipes, has shown that, apart from aberrant values associated with new pans on first use, the contribution made by 19% Cr/9% Ni stainless steel cooking utensils to chromium and nickel in the diet is negligible. New pans, if first used with acid fruits, showed a greater pick-up of chromium and nickel, ranging from approximately 1/20 to 1/3 and 1/20 to 1/2 of the normal daily intake of chromium and nickel respectively. This situation did not recur in subsequent usage, even after the pan had been cleaned by abrasion. A higher rate of chromium and nickel release in new pans on first use was observed on products from four manufactures and appears to be related to surface finish, since treatment of the surface of a new pan was partly, and in the case of electropolishing, wholly effective in eliminating their initial high release.

  13. Acute myelobalstic leukemia and hypercalcemia. A case of probable ectopic parathyroid hormone production.

    PubMed

    Zidar, B L; Shadduck, R K; Winkelstein, A; Zeigler, Z; Hawker, C D

    1976-09-23

    We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia. On six occasions during two years, hypercalcemia occurred in conjunction with relapses of leukmia. Each time, serum calcium decreased to normal levels in parallel with reduction of the leukemic mass. During two periods of hypercalcemia, immunoreactive parathyroid hormone values were abnormally high. In addition, hormone was detected in vitro after short-term incubation of the leukemic cells (after 24 hours, the patient's cells produced 129 pg of PTH per milliliter, whereas myeloblasts from a normocalcemic patient with leukemia produced only 33 pg). In freeze-thawing experiments, 39 pg of parathyroid hormone was released form 1 x 108 of the patient's myeloblasts; no hormone was released from the normocalcemia cells. These findings suggest that the hypercalcemia resulted from ectopic parathyroid hormone production by leukemic cells.

  14. The role of luteinizing hormone-releasing hormone in the diagnosis of constitutional delayed puberty

    PubMed Central

    Sagel, Julius; Distiller, Larry A.; Joffe, Barry I.

    1975-01-01

    The presumptive diagnosis of constitutional delayed adolescence is difficult to substantiate. Clinical examination and routine biochemical testing are not sufficient to exclude isolated gonadotrophin deficiency. Seven males are reported who presented with delayed puberty. These patients were given 100 μg luteinizing hormone-releasing hormone (LH-RH) intravenously, and the luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses were measured. Three of four males who were completely prepubertal (Stage 1) had a normal adult male response. These three patients have progressed further into puberty several months after this diagnostic test. The fourth patient in stage 1 puberty had a prepubertal LH response. A year later the response became adult in type, and 3 months thereafter stage 2 puberty was evident. The LH response to LH-RH thus appears to have some prognostic value in the assessment of males presenting with delayed puberty. PMID:1105498

  15. Effect of Magnesium Sulfate and Clonidine in Attenuating Hemodynamic Response to Pneumoperitoneum in Laparoscopic Cholecystectomy

    PubMed Central

    Kamble, Shruthi P.; Bevinaguddaiah, Yatish; Nagaraja, Dinesh Chillkunda; Pujar, Vinayak S.; Anandaswamy, Tejesh C.

    2017-01-01

    Background: Pneumoperitoneum in laparoscopic procedures is associated with hemodynamic response, due to the release of catecholamines and vasopressin. Magnesium and clonidine have been used to attenuate such hemodynamic responses by inhibiting release of these mediators. We conducted this randomized, double-blinded study to assess which of the two attenuates hemodynamic response better. Materials and Methods: Ninety American Society of Anesthesiologists health status Classes I and II patients posted for elective laparoscopic cholecystectomy were randomized into three groups of thirty patients each. Group C received injection clonidine 1 μg/kg diluted in 10 mL normal saline over 10 min, prior to pneumoperitoneum. Group M received injection magnesium sulfate 50 mg/kg diluted in 10 mL normal saline over 10 min, prior to pneumoperitoneum. Group NS received 10 mL normal saline intravenously over 10 min, prior to pneumoperitoneum. Hemodynamic parameters were recorded before induction (baseline values), at the end of magnesium sulfate/clonidine/saline administration and before pneumoperitoneum (P0), 5 min (P5), 10 min (P10), 20 min (P20), 30 min (P30), and 40 min (P40) after pneumoperitoneum. Results: Systolic blood pressure, diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were all significantly higher in the normal saline group compared to magnesium and clonidine. On comparing patients in Group M and Group C, DBP, MAP, and HR were significantly lower in the magnesium group. Mean extubation time and time to response to verbal commands were significantly longer in the magnesium group. Conclusions: Both magnesium and clonidine attenuated the hemodynamic response to pneumoperitoneum. However, magnesium 50 mg/kg, attenuated hemodynamic response better than clonidine 1 μg/kg. PMID:28298759

  16. Coordinated pH/redox dual-sensitive and hepatoma-targeted multifunctional polymeric micelle system for stimuli-triggered doxorubicin release: Synthesis, characterization and in vitro evaluation.

    PubMed

    Wang, Lele; Tian, Baocheng; Zhang, Jing; Li, Keke; Liang, Yan; Sun, Yujie; Ding, Yuanyuan; Han, Jingtian

    2016-03-30

    Multifunctional polymeric micelles self-assembled from a DOX-conjugated methoxypolyethylene glycols-b-poly (6-O-methacryloyl-D-galactopyranose)-disulfide bond-DOX (mPEG-b-PMAGP-SS-DOX) copolymer were prepared as an antitumor carrier for doxorubicin delivery, of which the chemical modification with disulfide bonds and hydrazone bonds allowed micelles to release doxorubicin (DOX) selectively at acidic pH and high redox conditions. The resulting micelles exhibited coordinated pH/redox dual-sensitive and hepatoma-targeted multifunction with sustaining stability in aqueous media. The multifunctional micelles showed spherical shapes with a mean diameter of 93 ± 2.08 nm, a low polydispersity index (PDI) of 0.21, a low CMC value of 0.095 mg/mL, a high drug grafting degree of 56.9% and a drug content of 39.0%. Remarkably, in vitro drug release studies clearly exhibited a pH and redox dual-sensitive drug release profile with significantly accelerated drug release treated with pH 5.0 and 10mM GSH (88.4% in 72 h) without drug burst release. The tumor proliferation assays indicated that DOX-grafted micelles, along with low cytotoxicity and well biocompatibility to normal cells up to a concentration of 10 μg/mL, inhibited the proliferation of HepG2 cells in a formulation-, time- and concentration-dependent manner in comparison with MCF-7 cells which was similar to free DOX. Anticancer activity releaved that the disulfide-modified micelles possessed much higher anti-hepatoma activity with a low IC50 value of 1.1 μg/mL following a 72 h incubation. Furthermore, the intracellular uptake tested by CLSM and FCM demonstrated that multifunctional polymeric micelles could be more efficiently taken up by HepG2 cells compared with MCF-7 cells, agreed well with MTT assays, suggesting these well-defined micelles provide a potential drug delivery system for dual-responsive controlled drug release and enhanced anti-hepatoma therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. The oxygen isotope composition of phosphate released from phytic acid by the activity of wheat and Aspergillus niger phytase

    NASA Astrophysics Data System (ADS)

    von Sperber, C.; Tamburini, F.; Brunner, B.; Bernasconi, S. M.; Frossard, E.

    2015-07-01

    Phosphorus (P) is an essential nutrient for living organisms. Under P-limiting conditions plants and microorganisms can exude extracellular phosphatases that release inorganic phosphate (Pi) from organic phosphorus compounds (Porg). Phytic acid (myo-inositol hexakisphosphate, IP6) is an important form of Porg in many soils. The enzymatic hydrolysis of IP6 by phytase yields available Pi and less phosphorylated inositol derivates as products. The hydrolysis of organic P compounds by phosphatases leaves an isotopic imprint on the oxygen isotope composition (δ18O) of released Pi, which might be used to trace P in the environment. This study aims at determining the effect of phytase on the oxygen isotope composition of released Pi. For this purpose, enzymatic assays with histidine acid phytases from wheat and Aspergillus niger were prepared using IP6, adenosine 5'-monophosphate (AMP) and glycerophosphate (GPO4) as substrates. For a comparison to the δ18O of Pi released by other extracellular enzymes, enzymatic assays with acid phosphatases from potato and wheat germ with IP6 as a substrate were prepared. During the hydrolysis of IP6 by phytase, four of the six Pi were released, and one oxygen atom from water was incorporated into each Pi. This incorporation of oxygen from water into Pi was subject to an apparent inverse isotopic fractionation (ϵ ~ 6 to 10 ‰), which was similar to that imparted by acid phosphatase from potato during the hydrolysis of IP6 (ϵ ~ 7 ‰), where less than three Pi were released. The incorporation of oxygen from water into Pi during the hydrolysis of AMP and GPO4 by phytase yielded a normal isotopic fractionation (ϵ ~ -12 ‰), similar to values reported for acid phosphatases from potato and wheat germ. We attribute this similarity in ϵ to the same amino acid sequence motif (RHGXRXP) at the active site of these enzymes, which leads to similar reaction mechanisms. We suggest that the striking substrate dependency of the isotopic fractionation could be attributed to a difference in the δ18O values of the C-O-P bridging and non-bridging oxygen atoms in organic phosphate compounds.

  18. The oxygen isotope composition of phosphate released from phytic acid by the activity of wheat and Aspergillus niger phytase

    NASA Astrophysics Data System (ADS)

    Sperber, C. v.; Tamburini, F.; Brunner, B.; Bernasconi, S. M.; Frossard, E.

    2015-03-01

    Phosphorus (P) is an essential nutrient for living organisms. Under P-limiting conditions plants and microorganisms can exude extracellular phosphatases that release inorganic phosphate (Pi) from organic phosphorus compounds (Porg). Phytic acid (IP6) is an important form of Porg in many soils. The enzymatic hydrolysis of IP6 by phytase yields plant available inorganic phosphate (Pi) and less phosphorylated inositol derivates as products. The hydrolysis of organic P-compounds by phosphatases leaves an isotopic imprint on the oxygen isotope composition (δ18O) of released Pi, which might be used to trace P in the environment. This study aims at determining the effect of phytase on the oxygen isotope composition of released Pi. For this purpose, enzymatic assays with histidine acid phytases from wheat and Aspergillus niger were prepared using IP6, adenosine 5'monophosphate (AMP) and glycerophosphate (GPO4) as substrates. For a comparison to the δ18O of Pi released by other extracellular enzymes, enzymatic assays with acid phosphatases from potato and wheat germ with IP6 as substrate were prepared. During the hydrolysis of IP6 by phytase, four Pi are released, and one oxygen atom from water is incorporated into each Pi. This incorporation of oxygen from water into Pi is subject to an apparent inverse isotopic fractionation (ϵ ∼ 6 to 10‰), which is similar to that imparted by acid phosphatase from potato during the hydrolysis of IP6 (ϵ ∼ 7‰) where less than three Pi are released. The incorporation of oxygen from water into Pi during the hydrolysis of AMP and GPO4 by phytase yielded a normal isotopic fractionation (ϵ ∼ -12‰), again similar to values reported for acid phosphatases from potato and wheat germ. We attribute this similarity in ɛ to the same amino acid sequence motif (RHGXRXP) at the active site of these enzymes, which leads to similar reaction mechanisms. We suggest that the striking substrate-dependency of the isotopic fractionation could be attributed to a difference in the δ18O-values of the C-O-P bridging and non-bridging oxygen atoms in organic phosphate compounds.

  19. Use of First-phase Insulin Secretion in Early Diagnosis of Thyroid Diabetes and Type 2 Diabetes Mellitus

    PubMed Central

    Meng, Li-Heng; Huang, Yao; Zhou, Jia; Liang, Xing-Huan; Xian, Jing; Li, Li; Qin, Ying-Fen

    2017-01-01

    Background: A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM. Methods: In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups. Furthermore, 96 patients without hyperthyroidism were recruited as control groups (normal glucose tolerance [NGT], impaired glucose regulation [IGR], and T2DM). The following parameters were evaluated: homeostasis model assessment (HOMA)-IR, HOMA-β, modified β-cell function index (MBCI), peak insulin/fasting insulin (IP/I0), AUCins-OGTT, and AUCins-OGTT/AUCglu-OGTT from the oral glucose tolerance test (OGTT) insulin release test were utilized to assess the second-phase insulin secretion, while the IP/I0, AIR0′~10′, and AUCins-IVGTT from the intravenous glucose tolerance test (IVGTT) insulin release test were used to assess the first-phase insulin secretion. Results: In the OGTT, the HOMA-β values of the TNGT and TDM groups were higher than those of the NGT and T2DM groups (all P < 0.05). In the hyperthyroidism groups, the MBCI of the TDM group was lower than that of the TNGT and TIGR groups (all P < 0.05). Among the control groups, the MBCI values of the IGR and T2DM groups were lower than that of the normal glucose tolerance (NGT) group (all P < 0.05). In the IVGTT, insulin secretion peaked for all groups at 2–4 min, except for the T2DM group, which showed a low plateau and no secretion peak. The IP values of the TNGT, TIGR, and TDM groups were higher than those of the NGT, IGR, and T2DM groups (all P < 0.05). The Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the TDM group were higher than those of the T2DM group but were lower than those of the TNGT, TIGR, NGR, and IGR groups (all P < 0.05). Compared with the other five groups, the Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the T2DM group were significantly decreased (all P < 0.05). The Ip/I0 and AUCins-IVGTT values of the TNGT group were higher than those of the NGT group (all P < 0.05). Conclusions: β-cell function in TDM patients is superior to that in T2DM patients. First-phase insulin secretion could be used as an early diagnostic marker to differentiate TDM and T2DM. PMID:28345543

  20. Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses.

    PubMed

    Aubrey, Karin R; Drew, Geoffrey M; Jeong, Hyo-Jin; Lau, Benjamin K; Vaughan, Christopher W

    2017-01-01

    The midbrain periaqueductal grey (PAG) forms part of an endogenous analgesic system which is tightly regulated by the neurotransmitter GABA. The role of endocannabinoids in regulating GABAergic control of this system was examined in rat PAG slices. Under basal conditions GABAergic neurotransmission onto PAG output neurons was multivesicular. Activation of the endocannabinoid system reduced GABAergic inhibition by reducing the probability of release and by shifting release to a univesicular mode. Blockade of endocannabinoid system unmasked a tonic control over the probability and mode of GABA release. These findings provides a mechanistic foundation for the control of the PAG analgesic system by disinhibition. The midbrain periaqueductal grey (PAG) has a crucial role in coordinating endogenous analgesic responses to physiological and psychological stressors. Endocannabinoids are thought to mediate a form of stress-induced analgesia within the PAG by relieving GABAergic inhibition of output neurons, a process known as disinhibition. This disinhibition is thought to be achieved by a presynaptic reduction in GABA release probability. We examined whether other mechanisms have a role in endocannabinoid modulation of GABAergic synaptic transmission within the rat PAG. The group I mGluR agonist DHPG ((R,S)-3,5-dihydroxyphenylglycine) inhibited evoked IPSCs and increased their paired pulse ratio in normal external Ca 2+ , and when release probability was reduced by lowering Ca 2+ . However, the effect of DHPG on the coefficient of variation and kinetics of evoked IPSCs differed between normal and low Ca 2+ . Lowering external Ca 2+ had a similar effect on evoked IPSCs to that observed for DHPG in normal external Ca 2+ . The low affinity GABA A receptor antagonist TPMPA ((1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid) inhibited evoked IPSCs to a greater extent in low than in normal Ca 2+ . Together these findings indicate that the normal mode of GABA release is multivesicular within the PAG, and that DHPG and lowering external Ca 2+ switch this to a univesicular mode. The effects of DHPG were mediated by mGlu5 receptor engagement of the retrograde endocannabinoid system. Blockade of endocannabinoid breakdown produced a similar shift in the mode of release. We conclude that endocannabinoids control both the mode and the probability of GABA release within the PAG. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  1. EMERALD-NORMAL; PWR activity release and dose. [IBM360,370; FORTRAN IV

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

    Gillespie, S.G.; Brunot, W.K.

    EMERALD-NORMAL is designed for the calculation of radiation releases and exposures resulting from normal operation of a large pressurized water reactor. The approach used is similar to an analog simulation of a real system. Each component or volume in the plant which contains a radioactive material is represented by a subroutine which keeps track of the production, transfer, decay, and absorption of radioactivity in that volume. During the course of the analysis, activity is transferred from subroutine to subroutine in the program as it would be transferred from place to place in the plant. Some of this activity is thenmore » released to the atmosphere and to the discharge canal. The rates of transfer, leakage, production, cleanup, decay, and release are read as input to the program. Subroutines are also included which calculate the off-site radiation exposures at various distances for individual isotopes and sums of isotopes. The program contains a library of physical data for the forty isotopes of most interest in licensing calculations, and other isotopes can be added or substituted. Because of the flexible nature of the simulation approach, the EMERALD-NORMAL program can be used for most calculations involving the production and release of radioactive material. These include design, operation, and licensing studies.IBM360,370; FORTRAN IV; OS/360,370; 576K bytes of memory.« less

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

    Fox, K. M.; Edwards, T. B.

    In this report, the Savannah River National Laboratory provides chemical analyses and Product Consistency Test (PCT) results for 14 simulated high level waste glasses fabricated by the Pacific Northwest National Laboratory. The results of these analyses will be used as part of efforts to revise or extend the validation regions of the current Hanford Waste Treatment and Immobilization Plant glass property models to cover a broader span of waste compositions. The measured chemical composition data are reported and compared with the targeted values for each component for each glass. All of the measured sums of oxides for the study glassesmore » fell within the interval of 96.9 to 100.8 wt %, indicating recovery of all components. Comparisons of the targeted and measured chemical compositions showed that the measured values for the glasses met the targeted concentrations within 10% for those components present at more than 5 wt %. The PCT results were normalized to both the targeted and measured compositions of the study glasses. Several of the glasses exhibited increases in normalized concentrations (NCi) after the canister centerline cooled (CCC) heat treatment. Five of the glasses, after the CCC heat treatment, had NC B values that exceeded that of the Environmental Assessment (EA) benchmark glass. These results can be combined with additional characterization, including X-ray diffraction, to determine the cause of the higher release rates.« less

  3. Pharmacokinetics of 2 Novel Formulations of Modified-Release Oral Testosterone Alone and With Finasteride in Normal Men With Experimental Hypogonadism

    PubMed Central

    Snyder, Christin N.; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Roth, Mara Y.; Page, Stephanie T.; Bremner, William J.; Amory, John K.

    2011-01-01

    Oral administration of testosterone might be useful for the treatment of testosterone deficiency. However, current “immediate-release” formulations of oral testosterone exhibit suboptimal pharmacokinetics, with supraphysiologic peaks of testosterone and its metabolite, dihydrotestosterone (DHT), immediately after dosing. To dampen these peaks, we have developed 2 novel modified-release formulations of oral testosterone designed to slow absorption from the gut and improve hormone delivery. We studied these testosterone formulations in 16 normal young men enrolled in a 2-arm, open-label clinical trial. Three hundred-mg and 600-mg doses of immediate-release and modified fast-release or slow-release formulations were administered sequentially to 8 normal men rendered hypogonadal by the administration of the gonadotropin-releasing hormone antagonist acyline. Blood for measurement of serum testosterone, DHT, and estradiol was obtained before and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after each dose. A second group of 8 men was studied with the coadministration of 1 mg of the 5α-reductase inhibitor finasteride daily throughout the treatment period. Serum testosterone was increased with all formulations of oral testosterone. The modified slow-release formulation significantly delayed the postdose peaks of serum testosterone and reduced peak concentrations of serum DHT compared with the immediate-release formulation. The addition of finasteride further increased serum testosterone and decreased serum DHT. We conclude that the oral modified slow-release testosterone formulation exhibits superior pharmacokinetics compared with immediate-release oral testosterone both alone and in combination with finasteride. This formulation might have efficacy for the treatment of testosterone deficiency. PMID:20378927

  4. Evidence for inhibitory nicotinic and facilitatory muscarinic receptors in cholinergic nerve terminals of the rat urinary bladder.

    PubMed

    Somogyi, G T; de Groat, W C

    1992-02-01

    Cholinergic prejunctional modulatory receptors on parasympathetic nerves in the rat urinary bladder were studied by measuring 3H-acetylcholine (ACh) release in muscle strips from the bladder body. Electrical field stimulation markedly increased 3H-ACh overflow in strips preloaded with 3H-choline. Oxotremorine (1 microM), an M2 receptor agonist and DMPP (10 microM) a nicotinic (N) receptor agonist decreased the release of ACh (50% and 55% respectively); whereas McN-A 343 (50 microM) an M1 receptor agonist increased the release (33%), indicating the presence of three types of modulatory receptors. The anticholinesterase agent, physostigmine in concentrations of 1, 5 and 25 microM and neostigmine (5 microM) increased ACh release (44-710%). However a low concentration of physostigmine (0.05 microM) decreased release. Pirenzepine, an M1 muscarinic antagonist or atropine blocked the increased ACh release in physostigmine-treated strips, but in normal strips pirenzepine did not change release and atropine increased release. McN-A 343 or prolonged application (15 min) of DMPP increased ACh release (376% and 391% respectively) in physostigmine-treated strips. The response to McN-A 343 was blocked by pirenzepine. d-Tubocurarine (DTC), a nicotinic receptor blocker, enhanced ACh release in the presence of physostigmine but proved to be ineffective in normal preparations. These findings suggest that all three cholinergic receptors (M1 facilitatory, N inhibitory and M2 inhibitory) are activated by endogenous ACh in physostigmine treated preparations whereas only M2-inhibitory receptors are activated in normal preparations. It will be important in future studies to determine whether M1 and M2 mechanisms can also be activated under more physiological conditions in the bladder and whether they are present at other cholinergic synapses.

  5. Assessment of subclinical acute kidney injury after abdominal aortic aneurysm surgery using novel markers: L-FABP and H-FABP.

    PubMed

    Kokot, Michał; Biolik, Grzegorz; Ziaja, Damian; Fojt, Tadeusz; Kędzierski, Leszek; Antoniak, Katarzyna; Janowska, Mirosława; Pawlicki, Krzysztof; Ziaja, Krzysztof; Duława, Jan

    2014-01-01

    One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Even small rises in serum creatinine are associated with increased mortality. The aim of this study was to assess the dynamics of AKI after elective AAA surgery using novel markers. The study group consisted of 22 patients with AAA. We measured urinary liver- (u-L-FABP) and heart-type fatty acid-binding proteins (u-H-FABP) before, during and within 3 days after surgery. We found an abrupt and significant elevation of both urine FABPs normalized to urinary creatinine; u-L-FABP reached its peak value 2 hours after aortic clamp release {137.79 (38.57-451.79) vs. 9.94 (6.82-12.42) ng/mg baseline value, p<0.05; values are medians (lower-upper quartile)}. The peak value of u-H-FABP was reported 72 hours after aortic clamp release {16.462 (4.182-37.595) vs. 0.141 (0.014-0.927) ng/mg baseline value, p<0.05}. The serum creatinine level did not changed significantly during the investigation period. The significant rise of both u-L-FABP and u-H-FABP after AAA surgery indicates renal proximal and distal tubule injury in this population. Our results suggest that, after AAA surgery, the distal tubules could be more affected than the proximal ones. u-FABPs could serve as sensitive biomarkers of kidney tubular injury and may allow to detect the very early phases of AKI.

  6. Desorption kinetics of hydrophobic organic chemicals from sediment to water: a review of data and models.

    PubMed

    Birdwell, Justin; Cook, Robert L; Thibodeaux, Louis J

    2007-03-01

    Resuspension of contaminated sediment can lead to the release of toxic compounds to surface waters where they are more bioavailable and mobile. Because the timeframe of particle resettling during such events is shorter than that needed to reach equilibrium, a kinetic approach is required for modeling the release process. Due to the current inability of common theoretical approaches to predict site-specific release rates, empirical algorithms incorporating the phenomenological assumption of biphasic, or fast and slow, release dominate the descriptions of nonpolar organic chemical release in the literature. Two first-order rate constants and one fraction are sufficient to characterize practically all of the data sets studied. These rate constants were compared to theoretical model parameters and functionalities, including chemical properties of the contaminants and physical properties of the sorbents, to determine if the trends incorporated into the hindered diffusion model are consistent with the parameters used in curve fitting. The results did not correspond to the parameter dependence of the hindered diffusion model. No trend in desorption rate constants, for either fast or slow release, was observed to be dependent on K(OC) or aqueous solubility for six and seven orders of magnitude, respectively. The same was observed for aqueous diffusivity and sediment fraction organic carbon. The distribution of kinetic rate constant values was approximately log-normal, ranging from 0.1 to 50 d(-1) for the fast release (average approximately 5 d(-1)) and 0.0001 to 0.1 d(-1) for the slow release (average approximately 0.03 d(-1)). The implications of these findings with regard to laboratory studies, theoretical desorption process mechanisms, and water quality modeling needs are presented and discussed.

  7. Dual turn-on fluorescence signal-based controlled release system for real-time monitoring of drug release dynamics in living cells and tumor tissues.

    PubMed

    Kong, Xiuqi; Dong, Baoli; Song, Xuezhen; Wang, Chao; Zhang, Nan; Lin, Weiying

    2018-01-01

    Controlled release systems with capabilities for direct and real-time monitoring of the release and dynamics of drugs in living systems are of great value for cancer chemotherapy. Herein, we describe a novel dual turn-on fluorescence signal-based controlled release system ( CDox ), in which the chemotherapy drug doxorubicin ( Dox ) and the fluorescent dye ( CH ) are conjugated by a hydrazone moiety, a pH-responsive cleavable linker. CDox itself shows nearly no fluorescence as the fluorescence of CH and Dox is essentially quenched by the C=N isomerization and N-N free rotation. However, when activated under acidic conditions, CDox could be hydrolyzed to afford Dox and CH , resulting in dual turn-on signals with emission peaks at 595 nm and 488 nm, respectively. Notably, CDox exhibits a desirable controlled release feature as the hydrolysis rate is limited by the steric hindrance effect from both the Dox and CH moieties. Cytotoxicity assays indicate that CDox shows much lower cytotoxicity relative to Dox , and displays higher cell inhibition rate to cancer than normal cells. With the aid of the dual turn-on fluorescence at different wavelengths, the drug release dynamics of CDox in living HepG2 and 4T-1 cells was monitored in double channels in a real-time fashion. Importantly, two-photon fluorescence imaging of CDox in living tumor tissues was also successfully performed by high-definition 3D imaging. We expect that the unique controlled release system illustrated herein could provide a powerful means to investigate modes of action of drugs, which is critical for development of much more robust and effective chemotherapy drugs.

  8. Self-immunity microcapsules for corrosion protection of steel bar in reinforced concrete

    NASA Astrophysics Data System (ADS)

    Wang, Yanshuai; Fang, Guohao; Ding, Weijian; Han, Ningxu; Xing, Feng; Dong, Biqin

    2015-12-01

    A novel microcapsule-based self-immunity system for reinforced concrete is proposed. Its feasibility for hindering the corrosion of steel rebar by means of lifting the threshold value of [Cl-]/[OH-] is discussed. Precisely controlled release behavior enables corrosion protection in the case of depassivation. The release process is characterized over a designated range of pH values, and its release characteristics of the microcapsules, triggered by decreasing pH value, are captured by observing that the core crystals are released when exposed to a signal (stimulus). The aim of corrosion protection of steel bar is achieved through the constantly-stabilized passive film, and its stability is promoted using continuous calcium hydroxide released from the microcapsule, restoring alkaline conditions. The test results exhibited that the release process of the microcapsules is a function of time. Moreover, the release rate of core materials could interact with environmental pH value, in which the release rate is found to increase remarkably with decreasing pH value, but is inhibited by high pH levels.

  9. Self-immunity microcapsules for corrosion protection of steel bar in reinforced concrete.

    PubMed

    Wang, Yanshuai; Fang, Guohao; Ding, Weijian; Han, Ningxu; Xing, Feng; Dong, Biqin

    2015-12-17

    A novel microcapsule-based self-immunity system for reinforced concrete is proposed. Its feasibility for hindering the corrosion of steel rebar by means of lifting the threshold value of [Cl(-)]/[OH(-)] is discussed. Precisely controlled release behavior enables corrosion protection in the case of depassivation. The release process is characterized over a designated range of pH values, and its release characteristics of the microcapsules, triggered by decreasing pH value, are captured by observing that the core crystals are released when exposed to a signal (stimulus). The aim of corrosion protection of steel bar is achieved through the constantly-stabilized passive film, and its stability is promoted using continuous calcium hydroxide released from the microcapsule, restoring alkaline conditions. The test results exhibited that the release process of the microcapsules is a function of time. Moreover, the release rate of core materials could interact with environmental pH value, in which the release rate is found to increase remarkably with decreasing pH value, but is inhibited by high pH levels.

  10. 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

  11. Divergent effects of bombesin and bethanechol on stimulated gastric secretion in duodenal ulcer and in normal men.

    PubMed

    Helman, C A; Hirschowitz, B I

    1987-06-01

    To further investigate differences in the responses of normals and patients with duodenal ulcer with respect to gastrin release and acid and pepsin secretion, we infused bombesin (1 microgram/kg X h) or bethanechol (40 micrograms/kg X h) during the middle hour of a 3-h infusion of pentagastrin and compared the results with a pentagastrin infusion without added drug. Pentagastrin dosage (0.1 microgram/kg X h) was set to give about half-maximal response, to detect either inhibition or further stimulation of gastric secretion, whereas the dose of bombesin was chosen to give maximal gastrin but less than maximal acid secretion. Serum gastrin and somatostatin were also measured. In all subjects tested, bethanechol produced no effects on acid, gastrin, or somatostatin release but increased pepsin output. By contrast, bombesin inhibited pentagastrin-stimulated acid output in all 6 normal men by an average of 55%, whereas it inhibited acid output in only 2 of the 9 men with duodenal ulcer. Serum gastrin increases after bombesin in duodenal ulcer were three to four times greater than in normals. Although bombesin stimulates acid only by releasing gastrin, we postulate that bombesin may also simultaneously limit acid and pepsin secretion and speculate that this effect could be mediated by bombesin-induced somatostatin release. The cause for differences between duodenal ulcer and normal remain speculative.

  12. Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone

    PubMed Central

    Costom, Bruce H.; Grumbach, Melvin M.; Kaplan, Selna L.

    1971-01-01

    To test the hypothesis that the primary defect in some patients with idiopathic hypopituitary dwarfism is failure to secrete hypothalamic hypophysiotropic-releasing factors, synthetic thyrotropin-releasing factor (TRF), 500 μg, wa given intravenously, and timed venous samples obtained for determination of the concentration of plasma TSH by radioimmunoassay in three groups of subjects: (a) 11 patients without evidence of endocrine or systemic disease, (group I) (b) 8 with isolated growth hormone deficiency and normal thyroid function, (group II) and (c) 9 patients with idiopathic hypopituitary dwarfism and thyroid-stimulating hormone (TSH) deficiency (group III). The mean fasting plasma TSH value was 4.1 μU/ml in group I, and 3.9 μU/ml in group II; in both groups there was a brisk rise in plasma TSH to peak levels of 12-45 μU/ml at 30-45 min, and a fall toward base line levels at 120 min. All children in group III had basal TSH levels of < 1.5 μU/ml; one failed to respond to TRF; eight exhibited a rise in plasma TSH with peak values comparable with those in groups I and II. In four of eight children in group III who responded to TRF, the TSH response was delayed and the initial rise in plasma TSH was not detectable until 10-60 min. In these four patients, plasma TSH levels continued to rise at 120 min. The mean fasting concentration of plasma thyroxine iodide (T4) in subjects with normal thyroid function (groups I and II) was 5.6 μg/100 ml, and the mean plasma T4 level at 120 min was 6.6 μg/100 ml. This difference between fasting and postTRF plasma T4 was significant (P < 0.001) by paired analysis. Mean fasting plasma T4 concentration in group III patients was 1.3 μg/100 ml; after TRF a significant rise in T4 concentration was not detected in this group. The results indicate that TRF test is useful in distinguishing between primary hypothalamic and pituitary forms of TSH deficiency. In light of the evidence of TRF deficiency in eight of nine patients with idiopathic hypopituitary dwarfism, it seems likely that in these patients, other pituitary hormone deficiencies may be attributable to deficiency of their respective releasing factors. Images PMID:4330007

  13. Does the Market Value Value-Added? Evidence from Housing Prices after a Public Release of School and Teacher Value-Added. Working Paper #47

    ERIC Educational Resources Information Center

    Imberman, Scott; Lovenheim, Michael F.

    2015-01-01

    Value-added data have become an increasingly common evaluation tool for schools and teachers. Many school districts have begun to adopt these methods and have released results publicly. In this paper, we use the unique public release of value-added data in Los Angeles to identify how this measure of school quality is capitalized into housing…

  14. Hydrostatic pressure activates ATP-sensitive K+ channels in lung epithelium by ATP release through pannexin and connexin hemichannels.

    PubMed

    Richter, Katrin; Kiefer, Kevin P; Grzesik, Benno A; Clauss, Wolfgang G; Fronius, Martin

    2014-01-01

    Lungs of air-breathing vertebrates are constantly exposed to mechanical forces and therefore are suitable for investigation of mechanotransduction processes in nonexcitable cells and tissues. Freshly dissected Xenopus laevis lungs were used for transepithelial short-circuit current (ISC) recordings and were exposed to increased hydrostatic pressure (HP; 5 cm fluid column, modified Ussing chamber). I(SC) values obtained under HP (I(5cm)) were normalized to values before HP (I(0cm)) application (I(5cm)/I(0cm)). Under control conditions, HP decreased I(SC) (I(5cm)/I(0cm)=0.84; n=68; P<0.0001). This effect was reversible and repeatable ≥30 times. Preincubation with ATP-sensitive K(+) channel (K(ATP)) inhibitors (HMR1098 and glibenclamide) prevented the decrease in I(SC) (I(5cm)/I(0cm): HMR1098=1.19, P<0.0001; glibenclamide=1.11, P<0.0001). Similar effects were observed with hemichannel inhibitors (I(5cm)/I(0cm): meclofenamic acid=1.09, P<0.0001; probenecid=1.0, P<0.0001). The HP effect was accompanied by release of ATP (P<0.05), determined by luciferin-luciferase luminescence in perfusion solution from the luminal side of an Ussing chamber. ATP release was abrogated by both meclofenamic acid and probenecid. RT-PCR experiments revealed the expression of pannexin and connexin hemichannels and KATP subunit transcripts in X. laevis lung. These data show an activation of KATP in pulmonary epithelial cells in response to HP that is induced by ATP release through mechanosensitive pannexin and connexin hemichannels. These findings represent a novel mechanism of mechanotransduction in nonexcitable cells.

  15. (14)C levels in the vicinity of the Fukushima Dai-ichi Nuclear Power Plant prior to the 2011 accident.

    PubMed

    Xu, Sheng; Cook, Gordon T; Cresswell, Alan J; Dunbar, Elaine; Freeman, Stewart P H T; Hastie, Helen; Hou, Xiaolin; Jacobsson, Piotr; Naysmith, Philip; Sanderson, David C W; Tripney, Brian G; Yamaguchi, Katsuhiko

    2016-06-01

    A 50-year-old Japanese cedar (Cryptomeria japonica) from Okuma, ∼1 km southwest of the Fukushima Dai-ichi Nuclear Power Plant, was cored and each annual ring was analysed for (14)C. The (14)C specific activity values varied from 330.4 Bq kg(-1) C in the tree ring formed in 1971 to 231.2 Bq kg(-1) C in the 2014 ring. During the periods 1971-1976 and 2011-2014, the (14)C specific activities are indistinguishable from the ambient background values. However, compared with the ambient atmospheric levels, the (14)C specific activities between 1977 and 2010 are significantly elevated, clearly indicating (14)C discharges from the reactors during their normal operations. In addition, the specific activities are positively correlated with the annual electricity generation values. The excess (14)C specific activities were <36 Bq kg(-1) C, corresponding to an additional annual effective dose of <2 μSv via the food ingestion pathway in the study location. The primary wind direction is east-southeast/southeast with a frequency of ∼30%, in comparison to ∼20% frequency for the direction of the site under study (north-northeast/northeast). This would tend to indicate a similar magnitude of additional effective dose and consequently no significant radiological impact of atmospheric (14)C discharges from the FDNPP during the entire period of normal operations. Additionally, no (14)C pulse in activity can be observed in the year 2011 ring. This might be caused by a limited (14)C release from the damaged reactors during the accident or that the prevailing wind during the short period of release (11th-25th March 2011) was not in the direction of Okuma. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Masking Release in Children and Adults With Hearing Loss When Using Amplification

    PubMed Central

    McCreery, Ryan; Kopun, Judy; Lewis, Dawna; Alexander, Joshua; Stelmachowicz, Patricia

    2016-01-01

    Purpose This study compared masking release for adults and children with normal hearing and hearing loss. For the participants with hearing loss, masking release using simulated hearing aid amplification with 2 different compression speeds (slow, fast) was compared. Method Sentence recognition in unmodulated noise was compared with recognition in modulated noise (masking release). Recognition was measured for participants with hearing loss using individualized amplification via the hearing-aid simulator. Results Adults with hearing loss showed greater masking release than the children with hearing loss. Average masking release was small (1 dB) and did not depend on hearing status. Masking release was comparable for slow and fast compression. Conclusions The use of amplification in this study contrasts with previous studies that did not use amplification. The results suggest that when differences in audibility are reduced, participants with hearing loss may be able to take advantage of dips in the noise levels, similar to participants with normal hearing. Although children required a more favorable signal-to-noise ratio than adults for both unmodulated and modulated noise, masking release was not statistically different. However, the ability to detect a difference may have been limited by the small amount of masking release observed. PMID:26540194

  17. Formation and characterization of β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated Fe3O4 nanoparticles for loading and releasing 5-Fluorouracil drug.

    PubMed

    Prabha, G; Raj, V

    2016-05-01

    In this work, β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated iron oxide nanoparticles (Fe3O4-β-CD-PEG-PEI) were developed as drug carriers for drug delivery applications. The 5- Fluorouracil (5-FU) was chosen as model drug molecule. The developed nanoparticles (Fe3O4-β-CD-PEG-PEI) were characterized by various techniques such as Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The average particles size range of 5-FU loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles were from 151 to 300nm and zeta potential value of nanoparticles were from -43mV to -20mV as measured using Malvern Zetasizer. Finally, encapsulation efficiency (EE), loading capacity (LC) and in-vitro drug release performance of 5-FU drug loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles was evaluated by UV-vis spectroscopy. In-vitro cytotoxicity tests investigated by MTT assay indicate that 5-FU loaded Fe3O4-β-CD-PEG-PEI nanoparticles were toxic to cancer cells and non-toxic to normal cells. The in-vitro release behavior of 5-FU from drug (5-FU) loaded Fe3O4-β-CD-PEG-PEI composite at different pH values and temperature was studied. It was found that 5-FU was released faster in pH 6.8 than in the acidic mediums (pH 1.2), and the released quantity was higher. Therefore, the newly prepared Fe3O4-β-CD-PEG-PEI carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

    PubMed

    Carlson, H E; Linfoot, J A; Braunstein, G D; Kovacs, K; Young, R T

    1983-05-01

    A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

  19. Advance regeneration in the Inland West: Considerations for individual tree and forest health

    Treesearch

    Dennis E. Ferguson

    1994-01-01

    Advance conifer regeneration readily survives release from overstory competition in the Inland West, but foresters are concerned about the ability of released trees to attain normal growth rates. There are also concerns about forest health issues associated with managing advance regeneration. The best pre-release predictors of post-release growth response are pre-...

  20. Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets.

    PubMed

    Reynolds, Thomas D; Mitchell, Shawn A; Balwinski, Karen M

    2002-04-01

    The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.

  1. Controlled-release tablet formulation of isoniazid.

    PubMed

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  2. Congenital hypothyroidism from complete iodide transport defect: long-term evolution with iodide treatment.

    PubMed Central

    Albero, R.; Cerdan, A.; Sanchez Franco, F.

    1987-01-01

    Hypothyroidism from iodide transport deficiency is a rare disease, especially when found in two affected siblings. Treatment with high doses of iodide has been recommended, but no long term results have been reported. Two siblings with congenital hypothyroidism due to total failure to transport iodide have been followed up during twelve and a half years of treatment with oral potassium iodide. Iodine doses varied between 10.3 and 22 mg/day, and serum total iodine concentrations between 100 and 210 micrograms/dl. Total triiodothyronine (T3), thyroxine (T4) and free T4 were in the normal range during the time of study. Basal thyroid stimulating hormones (TSH) and maximum TSH response to thyrotrophin releasing hormone (TRH) were also in the range of normal values. These data along with clinical findings confirmed the potential usefulness of iodine in hypothyroidism due to complete iodide transport defect. PMID:3451231

  3. Dialysate cancer antigen 125 concentration as marker of peritoneal membrane status in patients treated with chronic peritoneal dialysis.

    PubMed

    Krediet, R T

    2001-01-01

    This study reviews publications on the history of cancer antigen 125 (CA125), the background of its use as a marker of mesothelial cell mass, determination in peritoneal effluent, and its practical use in both the follow-up of peritoneal dialysis (PD) patients and as a marker of in vivo biocompatibility of dialysis solutions. Review article. CA125 is a high molecular weight glycoprotein. Previous studies in ascites suggested its release by mesothelial cells. In vitro studies with cultured mesothelial cells showed constitutive production, the majority of which was dependent on mesothelial cell mass. Serum CA125 is normal in PD patients, but its concentration in peritoneal dialysate suggests local release, probably from mesothelial cells. Effluent CA125 can be considered a marker of mesothelial cell mass in stable PD patients, but large amounts are found during peritonitis, due probably to necrosis of mesothelial cells. The majority of studies found no relationship between dialysate CA125 and peritoneal transport parameters. Some cross-sectional studies reported a relationship with duration of PD, but others were unable to confirm this, due probably to the large interindividual variability. Longitudinal follow-up has shown a decrease in dialysate CA125, indicating loss of mesothelial cell mass. Application of theoretically more-biocompatible PD solutions causes an increase in dialysate CA125. Dialysate CA125 is a mesothelial cell mass marker. The concentration of CA125 should be determined after a standardized dwell. A single low value is not informative. A decrease with time on PD suggests loss of mesothelial cell mass. Dialysate CA125 is a marker of in vivo biocompatibility of (new) dialysis solutions. More research is necessary on the best methodology for measuring low concentrations and establishing normal values and a significant change.

  4. Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

    PubMed

    Grossini, Elena; Farruggio, Serena; Qoqaiche, Fatima; Raina, Giulia; Camillo, Lara; Sigaudo, Lorenzo; Mary, David; Surico, Nicola; Surico, Daniela

    2016-09-15

    Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca(2+) transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca(2+)-ATPase pump inhibitors. The role of Na(+)/Ca(2+) exchanger was examined in experiments performed in zero Na(+) medium. NO release and intracellular Ca(2+) were measured through specific probes. In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca(2+)]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca(2+) mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na(+)/Ca(2+) exchanger and Ca(2+)-ATPase pump in restoring Ca(2+) was found. Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca(2+) transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Synthesis and colon-specific drug delivery of a poly(acrylic acid-co-acrylamide)/MBA nanosized hydrogel.

    PubMed

    Ray, Debajyoti; Mohapatra, Dillip K; Mohapatra, Ranjit K; Mohanta, Guru P; Sahoo, Prafulla K

    2008-01-01

    Intravenous administration of 5-fluorouracil (5-FU) for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The main objective of the present study was to develop novel oral site-specific delivery of 5-FU to the colon with less drug being released in the stomach or small intestine using biodegradable hydrogel, hydrogel nanoparticles and comparing the targeting efficiency of 5-FU to colon from both. Poly(acrylic acid-co-acrylamide) (P(AA-co-Am)) normal hydrogel and hydrogel nanoparticles (HN) were synthesized by free radical polymerization using N,N-methylene-bis-acrylamide (MBA) as cross-linker, potassium persulfate as reaction initiator and 5-FU was loaded. HN were found to be degradable in physiological medium and showed comparatively higher swelling in rat caecal medium (RCM). 5-FU entrapment was increased by increasing Am (wt%) monomer feed. In vitro release of 5-FU from normal hydrogel and HN in pH progressive medium, it was found that a AA/Am ratio of 25:75 showed higher release in RCM. The Higuchi model yielded good adjustment of in vitro release kinetics. A higher amount of 5-FU reached the colon in HN (61 +/- 2.1%) than normal hydrogel (40 +/- 3.6%) by organ biodistribution studies in albino rats.

  6. Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

    PubMed Central

    Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

    2013-01-01

    Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

  7. Chandra-SDSS Normal and Star-Forming Galaxies. I. X-Ray Source Properties of Galaxies Detected by the Chandra X-Ray Observatory in SDSS DR2

    NASA Astrophysics Data System (ADS)

    Hornschemeier, A. E.; Heckman, T. M.; Ptak, A. F.; Tremonti, C. A.; Colbert, E. J. M.

    2005-01-01

    We have cross-correlated X-ray catalogs derived from archival Chandra X-Ray Observatory ACIS observations with a Sloan Digital Sky Survey Data Release 2 (DR2) galaxy catalog to form a sample of 42 serendipitously X-ray-detected galaxies over the redshift interval 0.03

  8. Presence of gonadotropin-releasing hormone and its messenger ribonucleic acid in human ovarian epithelial carcinoma.

    PubMed

    Ohno, T; Imai, A; Furui, T; Takahashi, K; Tamaya, T

    1993-09-01

    The purpose of this study was to investigate the expression of gonadotropin-releasing hormone messenger ribonucleic acid and the presence of gonadotropin-releasing hormone in human ovarian carcinoma known to have gonadotropin-releasing hormone binding sites and to be affected by gonadotropin-releasing hormone analog. Human ovarian carcinomas surgically removed and human ovarian carcinoma cell lines were examined. Gonadotropin-releasing hormone was determined by a radioimmunoassay and a bioassay. Gonadotropin-releasing hormone messenger ribonucleic acid was determined by reverse transcription polymerase chain reaction using oligonucleotide primers synthesized according to the published human gonadotropin-releasing hormone sequence. Gonadotropin-releasing hormone was shown to be present in extracts of ovarian mucinous cystadenocarcinoma sample (0.8 +/- 0.12 pg/mg of protein) and ovarian adenocarcinoma cell line SK-OV3 (0.92 +/- 0.17 pg/mg of protein) but not in the normal ovary and placenta. Two of two extract samples from individual cases evoked dose-dependent phosphoinositide breakdown in rat granulosa cells similar to that caused by authentic gonadotropin-releasing hormone. Gonadotropin-releasing hormone messenger ribonucleic acid was detected in two of two mucinous cystadenocarcinoma specimens, one of one serous cystadenocarcinoma, and SK-OV3 cells but not in the dysgerminoma, mucinous cystadenoma, and normal ovary and placenta. The demonstration of gonadotropin-releasing hormone and its messenger ribonucleic acid raises the possibility that gonadotropin-releasing hormone may play an autocrine regulatory role in the growth of ovarian carcinoma.

  9. Congenital gonadotropin deficiency in boys: management during childhood.

    PubMed

    Adan, L; Couto-Silva, A C; Trivin, C; Metz, C; Brauner, R

    2004-02-01

    To analyze the features of boys with congenital gonadotropin deficiency (CGD), and to determine the value of plasma inhibin B and anti-Müllerian hormone (AMH) for predicting testicular function and the effect of testosterone treatment. We followed 19 boys for CGD, including five with Kallmann syndrome. The boys were seen before 14 years of age for micropenis (9 boys) or later for delayed puberty (10 boys). No testis was palpable in the scrotum in 13 patients, bilaterally in seven of them. Luteinizing hormone (LH) peak after a gonadotropin releasing hormone (GnRH) test was between 0.5 and 5.6 U/l. Plasma inhibin B was low in the four patients evaluated at less than 1 year old. AMH was low in one of them and normal in four others. Of the older patients, three lad low plasma inhibin B and four had normal concentrations; plasma AMH was low in three of them and increased in four. Testosterone treatment restored penis length to normal in all patients. Low plasma inhibin B and AMH concentrations may indicate testicular damage in boys with CGD.

  10. Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Neuronal GT1-7 Cell Line and Hypothalamic Explants

    EPA Science Inventory

    Gonadotrophin releasing hormone (GnRH) stimulates the release of pituitary luteinizing hormone (LH) and follicle stimulating hormone. These pituitary hormones are necessary for normal reproductive function in both males and females. It is well recognized that disruption of nor...

  11. 40 CFR 302.8 - Continuous releases.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... that the release is continuous and stable in quantity and rate; (2) Change in the normal range. If... section, continuous and stable in quantity and rate. (b) Definitions. The following definitions apply to... conditions during the preceding year. Only releases that are both continuous and stable in quantity and rate...

  12. Defining operating rules for mitigation of drought effects on water supply systems

    NASA Astrophysics Data System (ADS)

    Rossi, G.; Caporali, E.; Garrote, L.; Federici, G. V.

    2012-04-01

    Reservoirs play a pivotal role for water supply systems regulation and management especially during drought periods. Optimization of reservoir releases, related to drought mitigation rules is particularly required. The hydrologic state of the system is evaluated defining some threshold values, expressed in probabilistic terms. Risk deficit curves are used to reduce the ensemble of possible rules for simulation. Threshold values can be linked to specific actions in an operational context in different levels of severity, i.e. normal, pre-alert, alert and emergency scenarios. A simplified model of the water resources system is built to evaluate the threshold values and the management rules. The threshold values are defined considering the probability to satisfy a given fraction of the demand in a certain time horizon, and are validated with a long term simulation that takes into account the characteristics of the evaluated system. The threshold levels determine some curves that define reservoir releases as a function of existing storage volume. A demand reduction is related to each threshold level. The rules to manage the system in drought conditions, the threshold levels and the reductions are optimized using long term simulations with different hypothesized states of the system. Synthetic sequences of flows with the same statistical properties of the historical ones are produced to evaluate the system behaviour. Performances of different values of reduction and different threshold curves are evaluated using different objective function and performances indices. The methodology is applied to the urban area Firenze-Prato-Pistoia in central Tuscany, in Central Italy. The considered demand centres are Firenze and Bagno a Ripoli that have, accordingly to the census ISTAT 2001, a total of 395.000 inhabitants.

  13. Spatial Release From Masking in Simulated Cochlear Implant Users With and Without Access to Low-Frequency Acoustic Hearing

    PubMed Central

    Dietz, Mathias; Hohmann, Volker; Jürgens, Tim

    2015-01-01

    For normal-hearing listeners, speech intelligibility improves if speech and noise are spatially separated. While this spatial release from masking has already been quantified in normal-hearing listeners in many studies, it is less clear how spatial release from masking changes in cochlear implant listeners with and without access to low-frequency acoustic hearing. Spatial release from masking depends on differences in access to speech cues due to hearing status and hearing device. To investigate the influence of these factors on speech intelligibility, the present study measured speech reception thresholds in spatially separated speech and noise for 10 different listener types. A vocoder was used to simulate cochlear implant processing and low-frequency filtering was used to simulate residual low-frequency hearing. These forms of processing were combined to simulate cochlear implant listening, listening based on low-frequency residual hearing, and combinations thereof. Simulated cochlear implant users with additional low-frequency acoustic hearing showed better speech intelligibility in noise than simulated cochlear implant users without acoustic hearing and had access to more spatial speech cues (e.g., higher binaural squelch). Cochlear implant listener types showed higher spatial release from masking with bilateral access to low-frequency acoustic hearing than without. A binaural speech intelligibility model with normal binaural processing showed overall good agreement with measured speech reception thresholds, spatial release from masking, and spatial speech cues. This indicates that differences in speech cues available to listener types are sufficient to explain the changes of spatial release from masking across these simulated listener types. PMID:26721918

  14. Slow glucose release property of enzyme-synthesized highly branched maltodextrins differs among starch sources.

    PubMed

    Kittisuban, Phatcharee; Lee, Byung-Hoo; Suphantharika, Manop; Hamaker, Bruce R

    2014-07-17

    Seven types of starch (waxy corn, normal corn, waxy rice, normal rice, waxy potato, normal potato, and tapioca) were selected to produce slowly digestible maltodextrins by enzymatic modification using a previously developed procedure. Branching enzyme (BE) alone and in combination with β-amylase (BA) were used to increase the amount of α-1,6 branching points, which are slowly hydrolyzed by mucosal α-glucosidases in the small intestine. The enzymatic treatments of all starches resulted in a reduction of the debranched linear chain length distribution and weight-average molecular weight. After α-amylolysis of the enzymatically synthesized-maltodextrins, the proportion of branched α-limit dextrins increased, and consequently a reduction in rate of glucose release by rat intestinal α-glucosidases in vitro. Among the samples, enzyme-modified waxy starches had a more pronounced effect on an increase in the slow digestion property than normal starches. These enzyme-modified maltodextrins show potential as novel functional foods by slowing digestion rate to attain extended glucose release. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Regulation of exosome release from mammary epithelial and breast cancer cells - a new regulatory pathway.

    PubMed

    Riches, Andrew; Campbell, Elaine; Borger, Eva; Powis, Simon

    2014-03-01

    Exosomes are small 50-100nm sized extracellular vesicles released from normal and tumour cells and are a source of a new intercellular communication pathway. Tumour exosomes promote tumour growth and progression. What regulates the release and homoeostatic levels of exosomes, in cancer, in body fluids remains undefined. We utilised a human mammary epithelial cell line (HMEC B42) and a breast cancer cell line derived from it (B42 clone 16) to investigate exosome production and regulation. Exosome numbers were quantified using a Nanosight LM10 and measured in culture supernatants in the absence and presence of exosomes in the medium. Concentrated suspensions of exosomes from the normal mammary epithelial cells, the breast cancer cells and bladder cancer cells were used. The interaction of exosomes with tumour cells was also investigated using fluorescently labelled exosomes. Exosome release from normal human mammary epithelial cells and breast cancer cells is regulated by the presence of exosomes, derived from their own cells, in the extracellular environment of the cells. Exosomes from normal mammary epithelial cells also inhibit exosome secretion by breast cancer cells, which occurs in a tissue specific manner. Labelled exosomes from mammary epithelial cells are internalised into the tumour cells implicating a dynamic equilibrium and suggesting a mechanism for feedback control. These data suggest a previously unknown novel feedback regulatory mechanism for controlling exosome release, which may highlight a new therapeutic approach to controlling the deleterious effects of tumour exosomes. This regulatory mechanism is likely to be generic to other tumours. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. New best estimates for radionuclide solid-liquid distribution coefficients in soils. Part 2: naturally occurring radionuclides.

    PubMed

    Vandenhove, H; Gil-García, C; Rigol, A; Vidal, M

    2009-09-01

    Predicting the transfer of radionuclides in the environment for normal release, accidental, disposal or remediation scenarios in order to assess exposure requires the availability of an important number of generic parameter values. One of the key parameters in environmental assessment is the solid liquid distribution coefficient, K(d), which is used to predict radionuclide-soil interaction and subsequent radionuclide transport in the soil column. This article presents a review of K(d) values for uranium, radium, lead, polonium and thorium based on an extensive literature survey, including recent publications. The K(d) estimates were presented per soil groups defined by their texture and organic matter content (Sand, Loam, Clay and Organic), although the texture class seemed not to significantly affect K(d). Where relevant, other K(d) classification systems are proposed and correlations with soil parameters are highlighted. The K(d) values obtained in this compilation are compared with earlier review data.

  17. Controlled release of 18-β-glycyrrhetic acid by nanodelivery systems increases cytotoxicity on oral carcinoma cell line

    NASA Astrophysics Data System (ADS)

    Cacciotti, Ilaria; Chronopoulou, Laura; Palocci, Cleofe; Amalfitano, Adriana; Cantiani, Monica; Cordaro, Massimo; Lajolo, Carlo; Callà, Cinzia; Boninsegna, Alma; Lucchetti, Donatella; Gallenzi, Patrizia; Sgambato, Alessandro; Nocca, Giuseppina; Arcovito, Alessandro

    2018-07-01

    The topical treatment for oral mucosal diseases is often based on products optimized for dermatologic applications; consequently, a lower therapeutic effect may be present. 18-β-glycyrrhetic acid (GA) is extracted from Glycirrhiza glabra. The first aim of this study was to test the cytotoxicity of GA on PE/CA-PJ15 cells. The second aim was to propose and test two different delivery systems, i.e. nanoparticles and fibers, to guarantee a controlled release of GA in vitro. We used chitosan and poly(lactic-co-glycolic) acid based nanoparticles and polylactic acid fibers. We tested both delivery systems in vitro on PE/CA-PJ15 cells and on normal human gingival fibroblasts (HGFs). The morphology of GA-loaded nanoparticles (GA-NPs) and fibers (GA-FBs) was investigated by electron microscopy and dynamic light scattering; GA release kinetics was studied spectrophotometrically. MTT test was used to assess GA cytotoxicity on both cancer and normal cells. Cells were exposed to different concentrations of GA (20–500 μmol l‑1) administered as free GA (GA-f), and to GA-NPs or GA-FBs. ROS production was evaluated using dichlorodihydrofluorescein as a fluorescent probe. Regarding the cytotoxic effect of GA on PE/CA-PJ15 cells, the lowest TC50 value was 200 μmol l‑1 when GA was added as GA-NPs. No cytotoxic effects were observed when GA was administered to HGFs. N-acetyl Cysteine reduced mortality induced by GA-f in PE/CA-PJ15 cells. The specific effect of GA on PE/CA-PJ15 cells is mainly due to the different sensitivity of cancer cells to ROS over-production; GA-NPs and GA-FBs formulations increase, in vitro, this toxic effect on oral cancer cells.

  18. [Effect of glucocorticoides on the release of amino acids in the perfused rat hindquarter (author's transl)].

    PubMed

    Thienhaus, R; Tharandt, L; Zais, U; Staib, W

    1975-06-01

    The release of amino acids by skeletal muscle was studied in the isolated perfused rat hindquarter. Adrenalectomy depressed the formation of glutamine and alanine as well as the efflux of all other amino acids measured. Betamethasone--a synthetic glucocorticoid--caused a significant increase in the efflux of nearly all amino acids up to the level of normal controls. The release of amino acids was also increased in perfused hindquarters of diabetic rats. On the other hand, insulin exhibited a depressing effect on the release of amino acids by hindquarters of normal rats. The metabolic integrity of the muscle tissue was proved by measuring creatine phosphate, ATP, ADP and water content as well as by the significant insulin effect on glucose uptake and on [14C]leucine incorporation into muscle proteins.

  19. Potential highwall use by raptors in coal mine reclamation

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

    Waage, B.

    In 1982, Western Energy Company`s Rosebud Mine, located in southeastern Montana, received legal exception, {open_quotes}a first{close_quotes} in Montana to leave a standing mine highwall extending a native bluff. This bluff extension stands 110 feet high and 900 feet long. Normally, all highwalls by law are reduced to a 5:1 slope. This legal exception was accomplished with the support of several governmental agencies and was justified on the highwalls potential value for raptors. Enhancement measures undertaken on the highwall included the construction of three artificial eryies and the release of young prairie falcons (Falco mexicanus) employing hacking methods of the Peregrinemore » Fund. The hack is now in its fourth year with a total of 46 young falcons having been released. Opportunities exist for creating a more diverse habitat for raptors and other cliff obligate species on reclaimed mine lands in the west. It is believed that this practical approach should be explored.« less

  20. Mechanism of action of the levonorgestrel-releasing intrauterine system in the treatment of heavy menstrual bleeding.

    PubMed

    Cihangir, Uzunçakmak; Ebru, Akbay; Murat, Ekin; Levent, Yaşar

    2013-11-01

    To assess the efficacy and adverse effects, and reveal the effective pathway of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of heavy menstrual bleeding. In a prospective single-center study in Istanbul, Turkey, the LNG-IUS was inserted in 60 patients diagnosed with heavy menstrual bleeding between January 2008 and June 2010. Menstrual bleeding pattern, coagulation parameters, uterine arterial blood flow, endometrial thickness, and uterine and ovarian volumes were assessed pre-insertion, and at 6 and 12months. Forty-nine women completed the study. When compared with pre-insertion values, the LNG-IUS led to improvements in hemoglobin and marked decreases in visual bleeding scores, endometrial thickness, and fibrinogen levels (P<0.001); platelet count, international normalized ratio, prothrombin time, activated partial thromboplastin time, and uterine volume also decreased (P<0.05). No significant change in ovarian volumes, or uterine artery resistive and pulsatility indices was observed at 6 or 12months compared with pre-insertion values. The decline in menstrual blood loss among LNG-IUS users was associated with local progestogenic effects and aggravation of intrinsic and extrinsic coagulation pathways. Although the LNG-IUS is a highly effective method for treating heavy menstrual bleeding, care must be taken when a patient has thromboembolic risk factors. © 2013.

  1. Masking Release in Children and Adults with Hearing Loss When Using Amplification

    ERIC Educational Resources Information Center

    Brennan, Marc; McCreery, Ryan; Kopun, Judy; Lewis, Dawna; Alexander, Joshua; Stelmachowicz, Patricia

    2016-01-01

    Purpose: This study compared masking release for adults and children with normal hearing and hearing loss. For the participants with hearing loss, masking release using simulated hearing aid amplification with 2 different compression speeds (slow, fast) was compared. Method: Sentence recognition in unmodulated noise was compared with recognition…

  2. Listeners Experience Linguistic Masking Release in Noise-Vocoded Speech-in-Speech Recognition

    ERIC Educational Resources Information Center

    Viswanathan, Navin; Kokkinakis, Kostas; Williams, Brittany T.

    2018-01-01

    Purpose: The purpose of this study was to evaluate whether listeners with normal hearing perceiving noise-vocoded speech-in-speech demonstrate better intelligibility of target speech when the background speech was mismatched in language (linguistic release from masking [LRM]) and/or location (spatial release from masking [SRM]) relative to the…

  3. Luminal glucose concentrations in the gut under normal conditions.

    PubMed

    Ferraris, R P; Yasharpour, S; Lloyd, K C; Mirzayan, R; Diamond, J M

    1990-11-01

    Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), and the physiological role of active Glc transport and its regulation. Hence we measured luminal contents, osmolality, and Glc, Na+, and K+ concentrations in normally feeding rats, rabbits, and dogs. Measured Glc concentrations were compatible with the portion of measured osmolality not accounted for by Na+ and K+ salts, amino acids, and peptides. Mean SI luminal osmolalities were less than or equal to 100 mosmol/kg hypertonic. For animals on the most nearly physiological diets, SI Glc concentrations averaged 0.4-24 mM and ranged with time and SI region from 0.2 to a maximum of 48 mM. The older published very high values are artifacts of direct infusion of concentrated Glc solutions into the gut, nonspecific Glc assays, and failure to test for quantitative recovery or to centrifuge samples in the cold. By storing food after meals and releasing it between meals, rat stomach greatly damps diurnal fluctuations in quantity and osmolality of food reaching the SI and hence also damps fluctuations in absorption rates. These new values for luminal Glc have five important physiological implications: the problem of accounting for apparently very hypertonic SI contents in the face of high osmotic water permeability disappears; the effective Km of the SI Glc transporter is now comparable to prevailing Glc concentrations; the SI no longer appears to have enormous excess absorptive capacity for Glc; regulation of Glc transport by dietary intake now makes functional sense; and the claim that high luminal Glc concentrations permit solvent drag to become the major mode of Glc absorption under normal conditions is undermined.

  4. [Partial pressure of CO2 and CO2 degassing fluxes of Huayuankou and Xiaolangdi Station affected by Xiaolangdi Reservoir].

    PubMed

    Zhang, Yong-ling; Yang, Xiao-lin; Zhang, Dong

    2015-01-01

    According to periodic sampling analysis per month in Xiaolangdi station and Huayuankou station from November 2011 to October 2012, combined with continuous sampling analysis of Xiaolangdi Reservoir during runoff and sediment control period in 2012, partial pressure of CO2 (pCO2) in surface water were calculated based on Henry's Law, pCO2 features and air-water CO2 degassing fluxes of Huayuankou station and Xiaolangdi station affected by Xiaolangdi Reservoir were studied. The results were listed as follows, when Xiaolangdi Reservoir operated normally, pCO2 in surface water of Xiaolangdi station and Huayuankou station varied from 82 to 195 Pa and from 99 to 228 Pa, moreover, pCO2 in surface water from July to September were distinctly higher than those in other months; meanwhile, pCO, in surface water from Huayuankou station were higher than that from Xiaolangdi station. During runoff and sediment control period of Xiaolangdi Reservoir, two hydrological stations commonly indicated that pCO2 in surface water during water draining were obviously lower than those during sediment releasing. Whether in the period of normal operation or runoff and sediment control, pCO2 in surface water had positive relations to DIC content in two hydrological stations. Since the EpCO,/AOU value was higher than the theoretical value of 0. 62, the biological aerobic respiration effect had distinct contribution to pCO2. Throughout the whole year, air-water CO2 degassing fluxes from Xiaolangdi station and Huayuankou station were 0.486 p.mol (m2 s) -l and 0.588 pmol (m2 x s)(-1) respectively; When Xiaolangdi Reservoir operated normally, air-water CO, degassing fluxes in Huayuankou station were higher than that in Xiaolangdi station; during runoff and sediment control from Xiaolangdi Reservoir, two hydrological stations had one observation result in common, namely, air-water CO2 degassing fluxes in the period of water draining were obviously lower than that in the period of sediment releasing.

  5. The power of environment.

    PubMed

    Westbury, Becky

    2015-06-01

    In Ten tips for normal birth, the Royal College of Midwives (RCM) (2014) advocates the building of nests; creating an environment that helps women to feel safe and secure during birth, as this can improve women's experiences and likelihood of normal birth. Furthermore, a private, undisturbed and dark environment, where women feel calm and safe can promote the release of oxytocin, the hormone responsible for uterine contractions and thought to promote the release of the pain relieving hormones endorphins (Uvnas Moberg 2003). When this is not achieved, women can experience fear-tension-pain syndrome, impeding labour progress and causing increased levels of pain (Dick-Read 2013). In addition, birth space has the potential to encourage the promotion of normality through providing space to mobilise, and alternative furniture to enable upright birth positions. Midwives should help women to create a birth space in which they feel safe, calm and secure, to promote normality and increase the incidence of normal birth (RCM 2014).

  6. Pro-Gastrin Releasing Peptide: A New Serum Marker for Endometrioid Adenocarcinoma.

    PubMed

    Kiseli, Mine; Caglar, Gamze Sinem; Yarci Gursoy, Asli; Tasci, Tolga; Candar, Tuba; Akincioglu, Egemen; Pabuccu, Emre Goksan; Boran, Nurettin; Tulunay, Gokhan; Umudum, Haldun

    2018-06-13

    Gastrin-releasing peptide (GRP) is thought to play a role in the metastatic process of various malignancies. The more stable precursor of GRP, pro-GRP (ProGRP), has been shown to be secreted by neuroendocrine tumors. This study was designed to assess the validity of ProGRP as a diagnostic marker in endometrioid adenocarcinomas (EAs) of the endometrium. Thirty-seven patients with a diagnosis of EA, 23 patients with endometrial hyperplasia, and 32 age-matched controls with normal endometrial histology were recruited for this study. Serum ProGRP and cancer antigen 125 (CA125) values were compared between groups. Median serum ProGRP levels were significantly higher in the cancer group compared to corresponding levels in both the hyperplasia and control groups (p = 0.008 and p < 0.001 respectively; endometrial cancer: 27.5 pg/mL; hyperplasia: 16.1 pg/mL; controls: 12.9 pg/mL). Age and endometrial thickness were positively correlated with ProGRP levels (r = 0.322, p = 0.006 and r = 0.269, p = 0.023, respectively). Receiver Operating Characteristic curve analyses for EA revealed a threshold of 20.81 pg/mL, with a sensitivity of 60.7% and specificity of 81.4%, positive predictive value of 68% and negative predictive value of 76.1%. Significantly higher ProGRP levels were observed in patients with EA than in controls. Serum ProGRP has good diagnostic sensitivity and specificity for EA. © 2018 S. Karger AG, Basel.

  7. Preparation and evaluation of a controlled drug release of repaglinide through matrix pellets: in vitro and in vivo studies.

    PubMed

    Tavakoli, Naser; Minaiyan, Mohsen; Tabbakhian, Majid; Pendar, Yaqub

    2014-01-01

    Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1 h. Designing a controlled release dosage form of the drug is required to maintain its therapeutic blood level and to eliminate its adverse effects, particularly the hypoglycaemia. Repaglinide sustained release matrix pellets consisting of Avicel, lactose and different polymers were prepared using extrusion-spheronisation method. The effect of different formulation components on in vitro drug release were evaluated using USP apparatus (paddle) for 12 h in phosphate buffer. The optimised formulation was orally administrated to normal and STZ induced diabetic rats. Most pellet formulations had acceptable physical properties with regard to size distribution, flowability and friability. Repaglinide pellets comprising Avicel 50%, lactose 47% and SLS 1% were released 94% of its drug content after 12 h. The optimised formulation was able to decrease blood glucose level in normal rats and those with diabetes throughout 8-12 h.

  8. Congenital isolated thyrotrophin releasing hormone deficiency

    PubMed Central

    Niimi, H; Inomata, H; Sasaki, N; Nakajima, H

    1982-01-01

    A 4⅓-year-old girl with congenital thyrotrophin-releasing hormone (TRH) deficiency is described. Oral TRH administration led to normal thyroid hormone and TRH levels in the blood; favourable growth and development was achieved. PMID:6816148

  9. Can We Really "Feel" a Balanced Total Knee Arthroplasty?

    PubMed

    Elmallah, Randa K; Mistry, Jaydev B; Cherian, Jeffrey J; Chughtai, Morad; Bhave, Anil; Roche, Martin W; Mont, Michael A

    2016-09-01

    Balancing techniques in total knee arthroplasty are often based on surgeons' subjective judgment. However, newer technologies have allowed for objective measurements of soft tissue balancing. This study compared the use of sensor technology to the 30-year surgeon experience regarding (1) compartment loads, (2) soft tissue releases, and (3) component rotational alignments. Patients received either sensor-guided soft tissue balancing (n = 10) or manual gap balancing (n = 12). Wireless, intraoperative sensor tibial inserts were used to measure intracompartmental loads. The surgeon was blinded to values in the manual gap-balancing cohort. In the sensor cohort, the surgeon was unblinded, and implant trials were placed after normal releases were performed to guide further ligament releases after femoral and tibial resections, as needed. Load measurements were taken at 10°, 45°, and 90°. The sensor cohort had lower medial and lateral compartment loading at 10°, 45°, and 90°. The sensor group had lower mean differences in intercompartment loading at 10° (-5.6 vs -51.7 lbs), 45° (-9.8 vs -45.9 lbs), and 90° (-4.3 vs -27 lbs) compared to manually balanced patients. There were 10 additional soft tissue releases in the sensor cohort (2 initial ones before sensor use), compared to 2 releases in the gap-balanced cohort. In the gap-balanced cohort, tibial trays were positioned at a mean 9° external rotation, compared to a mean 1° internal rotation in the sensor-guided cohort. Sensor-balanced total knee arthroplasties provide objective feedback to perform releases and potentially improve knee balancing and rotational alignment. Future work may clarify whether these changes are beneficial for our patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis: effects of drugs affecting noradrenergic transmission.

    PubMed

    L'Heureux, R; Dennis, T; Curet, O; Scatton, B

    1986-06-01

    The release of endogenous noradrenaline was measured in the cerebral cortex of the halothane-anesthetized rat by using the technique of brain dialysis coupled to a radioenzymatic assay. A thin dialysis tube was inserted transversally in the cerebral cortex (transcortical dialysis) and perfused with Ringer medium (2 microliter min-1). Under basal conditions, the cortical output of noradrenaline was stable over a period of at least 6 h and amounted to 8.7 pg/20 min (not corrected for recovery). Histological control of the perfused area revealed very little damage and normal morphology in the vicinity of the dialysis tube. Omission of calcium from the perfusion medium caused a marked drop in cortical noradrenaline output. Bilateral electrical stimulation (for 10 min) of the ascending noradrenergic pathways in the medial forebrain bundle caused a frequency-dependent increase in cortical noradrenaline output over the range 5-20 Hz. Stimulation at a higher frequency (50 Hz) resulted in a levelling off of the increase in cortical noradrenaline release. Systemic administration of the dopamine-beta-hydroxylase inhibitor bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA 63) (25 mg/kg i.p.) markedly reduced, whereas injection of the monoamine oxidase inhibitor pargyline (75 mg/kg i.p.) resulted in a progressive increase in, cortical noradrenaline output. d-Amphetamine (2 mg/kg i.p.) provoked a sharp increase in cortical noradrenaline release (+450% over basal values within 40 min). Desmethylimipramine (10 mg/kg i.p.) produced a twofold increase of cortical noradrenaline release. Finally, idazoxan (20 mg/kg i.p.) and clonidine (0.3 mg/kg i.p.), respectively, increased and decreased the release of noradrenaline from the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Pharmacokinetics of Modified Slow-Release Oral Testosterone Over 9 Days in Normal Men With Experimental Hypogonadism

    PubMed Central

    Lee, Ada; Rubinow, Katya; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Zhi, Hui; Roth, Mara Y; Page, Stephanie T.; Bremner, William J.; Amory, John K.

    2014-01-01

    Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 µg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone–binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P > .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency. PMID:21868746

  12. Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line.

    PubMed

    Chappell, Patrick E; White, Rachel S; Mellon, Pamela L

    2003-12-03

    Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse hypothalamic cell line as a model for GnRH secretion, because these cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1-7 cells by transient expression of the dominant-negative Clock-Delta19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.

  13. Launch Lock Assemblies Including Axial Gap Amplification Devices and Spacecraft Isolation Systems Including the Same

    NASA Technical Reports Server (NTRS)

    Barber, Tim Daniel (Inventor); Hindle, Timothy (Inventor); Young, Ken (Inventor); Davis, Torey (Inventor)

    2014-01-01

    Embodiments of a launch lock assembly are provided, as are embodiments of a spacecraft isolation system including one or more launch lock assemblies. In one embodiment, the launch lock assembly includes first and second mount pieces, a releasable clamp device, and an axial gap amplification device. The releasable clamp device normally maintains the first and second mount pieces in clamped engagement; and, when actuated, releases the first and second mount pieces from clamped engagement to allow relative axial motion there between. The axial gap amplification device normally residing in a blocking position wherein the gap amplification device obstructs relative axial motion between the first and second mount pieces. The axial gap amplification device moves into a non-blocking position when the first and second mount pieces are released from clamped engagement to increase the range of axial motion between the first and second mount pieces.

  14. Metabolic influence of lead on polyhydroxyalkanoates (PHA) production and phosphate uptake in activated sludge fed with glucose or acetic acid as carbon source.

    PubMed

    You, Sheng-Jie; Tsai, Yung-Pin; Cho, Bo-Chuan; Chou, Yi-Hsiu

    2011-09-01

    Sludge in a sequential batch reactor (SBR) system was used to investigate the effect of lead toxicity on metabolisms of polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs) communities fed with acetic acid or glucose as their sole carbon source, respectively. Results showed that the effect of lead on substrate utilization of both PAOs and GAOs was insignificant. However, lead substantially inhibited both of phosphate release and uptake of PAOs. In high concentration of acetic acid trials, an abnormal aerobic phosphate release was observed instead of phosphate uptake and the release rate increased with increasing lead concentration. Results also showed that PAOs could normally synthesize polyhydroxybutyrate (PHB) in the anaerobic phase even though lead concentration was 40 mg L(-1). However, they could not aerobically utilize PHB normally in the presence of lead. On the other hand, GAOs could not normally metabolize polyhydroxyvalerate (PHV) in both the anaerobic and aerobic phases. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Differential effects of cyclic and constant stress on ATP release and mucociliary transport by human airway epithelia

    PubMed Central

    Button, Brian; Picher, Maryse; Boucher, Richard C

    2007-01-01

    In the lungs, the first line of defence against bacterial infection is the thin layer of airway surface liquid (ASL) lining the airway surface. The superficial airway epithelium exhibits complex regulatory pathways that blend ion transport to adjust ASL volume to maintain proper mucociliary clearance (MCC). We hypothesized that stresses generated by airflow and transmural pressures during breathing govern ASL volume by regulating the rate of epithelial ATP release. Luminal ATP, via interactions with apical membrane P2-purinoceptors, regulates the balance of active ion secretion versus absorption to maintain ASL volume at optimal levels for MCC. In this study we tested the hypothesis that cyclic compressive stress (CCS), mimicking normal tidal breathing, regulates ASL volume in airway epithelia. Polarized tracheobronchial epithelial cultures from normal and cystic fibrosis (CF) subjects responded to a range of CCS by increasing the rate of ATP release. In normal airway epithelia, the CCS-induced increase in ASL ATP concentration was sufficient to induce purinoceptor-mediated increases in ASL height and MCC, via inhibition of epithelial Na+-channel-mediated Na+ absorption and stimulation of Cl− secretion through CFTR and the Ca2+-activated chloride channels. In contrast, static, non-oscillatory stress did not stimulate ATP release, ion transport or MCC, emphasizing the importance of rhythmic mechanical stress for airway defence. In CF airway cultures, which exhibit basal ASL depletion, CCS was partially effective, producing less ASL volume secretion than in normal cultures, but a level sufficient to restore MCC. The present data suggest that CCS may (1) regulate ASL volume in the normal lung and (2) improve clearance in the lungs of CF patients, potentially explaining the beneficial role of exercise in lung defence. PMID:17317749

  16. Experimental and computational correlation of fracture parameters KIc, JIc, and GIc for unimodular and bimodular graphite components

    NASA Astrophysics Data System (ADS)

    Bhushan, Awani; Panda, S. K.

    2018-05-01

    The influence of bimodularity (different stress ∼ strain behaviour in tension and compression) on fracture behaviour of graphite specimens has been studied with fracture toughness (KIc), critical J-integral (JIc) and critical strain energy release rate (GIc) as the characterizing parameter. Bimodularity index (ratio of tensile Young's modulus to compression Young's modulus) of graphite specimens has been obtained from the normalized test data of tensile and compression experimentation. Single edge notch bend (SENB) testing of pre-cracked specimens from the same lot have been carried out as per ASTM standard D7779-11 to determine the peak load and critical fracture parameters KIc, GIc and JIc using digital image correlation technology of crack opening displacements. Weibull weakest link theory has been used to evaluate the mean peak load, Weibull modulus and goodness of fit employing two parameter least square method (LIN2), biased (MLE2-B) and unbiased (MLE2-U) maximum likelihood estimator. The stress dependent elasticity problem of three-dimensional crack progression behaviour for the bimodular graphite components has been solved as an iterative finite element procedure. The crack characterizing parameters critical stress intensity factor and critical strain energy release rate have been estimated with the help of Weibull distribution plot between peak loads versus cumulative probability of failure. Experimental and Computational fracture parameters have been compared qualitatively to describe the significance of bimodularity. The bimodular influence on fracture behaviour of SENB graphite has been reflected on the experimental evaluation of GIc values only, which has been found to be different from the calculated JIc values. Numerical evaluation of bimodular 3D J-integral value is found to be close to the GIc value whereas the unimodular 3D J-value is nearer to the JIc value. The significant difference between the unimodular JIc and bimodular GIc indicates that GIc should be considered as the standard fracture parameter for bimodular brittle specimens.

  17. Long-suppressed ponderosa pine seedlings respond to release.

    Treesearch

    Walter G. Dahms

    1960-01-01

    Long-suppressed ponderosa pine seedlings and saplings have a remarkable ability to recover and resume normal growth when released. This fact is strikingly demonstrated by a study begun in 1934 on the Pringle Falls Experimental Forest, near Bend, Oregon.

  18. 33 CFR 208.22 - Twin Buttes Dam and Reservoir, Middle and South Concho Rivers, Tex.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and releases; uncontrolled spillway releases; storage; reservoir inflow; available evaporation data.... Normally, one reading at 8 a.m. shall be shown for each day. Readings of all items except evaporation shall...

  19. 33 CFR 208.22 - Twin Buttes Dam and Reservoir, Middle and South Concho Rivers, Tex.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and releases; uncontrolled spillway releases; storage; reservoir inflow; available evaporation data.... Normally, one reading at 8 a.m. shall be shown for each day. Readings of all items except evaporation shall...

  20. 33 CFR 208.22 - Twin Buttes Dam and Reservoir, Middle and South Concho Rivers, Tex.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and releases; uncontrolled spillway releases; storage; reservoir inflow; available evaporation data.... Normally, one reading at 8 a.m. shall be shown for each day. Readings of all items except evaporation shall...

  1. Carboxymethylcellulose-tetrahydrocurcumin conjugates for colon-specific delivery of a novel anti-cancer agent, 4-amino tetrahydrocurcumin.

    PubMed

    Plyduang, Thipapun; Lomlim, Luelak; Yuenyongsawad, Supreeya; Wiwattanapatapee, Ruedeekorn

    2014-10-01

    Several curcumin derivatives are now becoming increasingly of interest because of their bioactive attributes, especially their action as antioxidants and anti-carcinogenic activities. Tetrahydrocurcumin (THC), an active metabolite of curcumin, was selected to be a proper starting material for the work presented here as it is stable in physiological pH and has the typical pharmacological properties of curcumin. We have now reported that novel synthesized water-soluble polymeric macromolecule prodrugs can specifically deliver the drug to the colon. To study the drug loading and drug release, THC was conjugated with a hydrophilic polymer, carboxymethylcellulose (CMC) with the degree of substitution (DS) values of 0.7 and 1.2. THC was also attached to two different spacers including p-aminobenzoic acid (PABA) and p-aminohippuric acid (PAH) via an azo bond that was cleaved by the azoreductase activities of colonic bacteria. The novel active molecule, 4-amino-THC, was readily released from the conjugates in the colon (>62% within 24h) with only very small amounts released in the upper GI tract (<12% over 12h). The polymer conjugates showed chemical stability at various pH values along the gastrointestinal tract and increased water solubility of up to 5mg/mL. 4-Amino-THC demonstrated cytotoxic ability against the human colon adenocarcinoma cell lines (HT-29) with an IC50 of 28.67 ± 1.01 μg/mL, and even greater selectivity (∼ 4 folds) to inhibit HT-29 cells than to normal human colon epithelial cell lines while curcumin was a non-selective agent against both cell lines. Our study has demonstrated that the use of THC-CMC conjugates may be a promising colon-specific drug delivery system with its sustained release in the colon to be an effective treatment for colonic cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Hydrocolloid-based nutraceutical delivery systems

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

    Janaswamy, Srinivas; Youngren, Susanne R.

    Nutraceuticals are important due to their inherent health benefits. However, utilization and consumption are limited by their poor water solubility and instability at normal processing and storage conditions. Herein, we propose an elegant and novel approach for the delivery of nutraceuticals in their active form using hydrocolloid matrices that are inexpensive and non-toxic with generally recognized as safe (GRAS) status. Iota-carrageenan and curcumin have been chosen as models of hydrocolloid and nutraceutical compounds, respectively. The iota-carrageenan network maintains a stable organization after encapsulating curcumin molecules, protects them from melting and then releases them in a sustained manner. These findings laymore » a strong foundation for developing value-added functional and medicinal foods.« less

  3. Multi-unit dosage formulations of theophylline for controlled release applications.

    PubMed

    Uhumwangho, Michael U; Okor, Roland S

    2007-01-01

    The study was carried out to investigate the drug release profiles of multi-unit dosage formulations of theophylline consisting of both the fast and slow release components in a unit dose. The fast release component consisted of conventional granules of theophylline formed by mixing the drug powder with starch mucilage (20% w/v) while the slow release component consisted of wax granulations of theophylline formed by triturating the drug powder with a melted Carnauba wax (drug:wax ratio, 4:1). The granules were either filled into capsules or tabletted. In the study design, the drug release characteristics of the individual fast or slow release particles were first determined separately and then mixed in various proportions for the purpose of optimizing the drug release profiles. The evaluating parameters were the prompt release in the first 1 h (mp), the maximum release (m infinity) and the time to attain it (t infinity). Total drug content in each capsule or tablet was 300 mg and two of such were used in dissolution studies. The release kinetics and hence the release mechanism was confirmed by measuring the linear regression coefficient (R2 values) of the release data. The release kinetics was generally most consistent with the Higuchi square root of time relationship (R2 = 0.95). indicating a diffusion-controlled mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while for the capsules and tablets of the wax granulations mp and t infinity values were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a combination of wax granulation and tableting markedly retarded drug release. In the multi-unit dose formulations where the conventional and wax granulations were mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7 h), reSpectively. The corresponding values of m infinity and t infinity for the tablets were (240 mg, 9 h), (180 mg, 11 h) and (128 mg, 12 h) against the set target (200 mg, 12 h). The indication is that tableting rather than encapsulation can more effectively control drug release from the systems.

  4. Piezo1 regulates mechanotransductive release of ATP from human RBCs.

    PubMed

    Cinar, Eyup; Zhou, Sitong; DeCourcey, James; Wang, Yixuan; Waugh, Richard E; Wan, Jiandi

    2015-09-22

    Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca(2+)) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca(2+) influx decrease significantly. Remarkably, a critical extracellular Ca(2+) concentration is required to trigger significant ATP release, but membrane-associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease.

  5. [Anthology of the first clinical studies with hypothalamic hormones: a story of successful international cooperation].

    PubMed

    Schally, Andrew V; Gual, Carlos

    2002-01-01

    Our early pioneering clinical trials in Mexico with natural and synthetic thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Highly purified TRH of porcine origin was shown to stimulate Thyrotropin (TSH) release in hypothyroid cretins. Subsequent tests with synthetic TRH also demonstrated significant increases in plasma TSH in normal men and women as well as in patients with primary hypothyroidism and other endocrine disorders. Even more extensive clinical studies were carried out with highly purified natural porcine LH-RH. Subjects with normal basal serum levels of gonadotropins, low levels (men and women pretreated with steroids) and high levels (e.g. post menopausal women) all responded to LH-RH with a release of LH and FSH. The results of these early studies with the natural LH-RH were confirmed by the use of synthetic LH-RH. These investigations made in Mexico with TRH and LH-RH preceded all other clinical studies by a wide margin. Subsequently various clinical investigations with LH-RH agonists and antagonists were also carried out. All these studies played a major role in introducing hypothalamic-releasing hormones into clinical medicine.

  6. Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis

    PubMed Central

    2017-01-01

    Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value. PMID:28930162

  7. Effects of Long-Term Cranberry Supplementation on Endocrine Pancreas in Aging Rats

    PubMed Central

    Zhu, Min; Hu, Jingping; Perez, Evelyn; Phillips, Dawn; Kim, Wook; Ghaedian, Reza; Napora, Joshua K.

    2011-01-01

    The effects of long-term cranberry consumption on age-related changes in endocrine pancreas are not fully understood. Here we treated male Fischer 344 rats with either 2% whole cranberry powder supplemented or normal rodent chow from 6 to 22 month old. Both groups displayed an age-related decline in basal plasma insulin concentrations, but this age-related decline was delayed by cranberry. Cranberry supplementation led to increased β-cell glucose responsiveness during the oral glucose tolerance test. Portal insulin concentration was 7.6-fold higher in rats fed cranberry, coupled with improved β-cell function. However, insulin resistance values were similar in both groups. Total β-cell mass and expression of pancreatic and duodenal homeobox 1 and insulin within islets were significantly enhanced in rats fed cranberry relative to controls. Furthermore, cranberry increased insulin release of an insulin-producing β-cell line, revealing its insulinotropic effect. These findings suggest that cranberry is of particular benefit to β-cell function in normal aging rats. PMID:21768504

  8. Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis.

    PubMed

    Ingenbleek, Yves

    2017-09-20

    Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value.

  9. How clarinettists articulate: The effect of blowing pressure and tonguing on initial and final transients.

    PubMed

    Li, Weicong; Almeida, André; Smith, John; Wolfe, Joe

    2016-02-01

    Articulation, including initial and final note transients, is important to tasteful music performance. Clarinettists' tongue-reed contact, the time variation of the blowing pressure P¯mouth, the mouthpiece pressure, the pressure in the instrument bore, and the radiated sound were measured for normal articulation, accents, sforzando, staccato, and for minimal attack, i.e., notes started very softly. All attacks include a phase when the amplitude of the fundamental increases exponentially, with rates r ∼1000 dB s(-1) controlled by varying both the rate of increase in P¯mouth and the timing of tongue release during this increase. Accented and sforzando notes have shorter attacks (r∼1300 dB s(-1)) than normal notes. P¯mouth reaches a higher peak value for accented and sforzando notes, followed by a steady decrease for accented notes or a rapid fall to a lower, nearly steady value for sforzando notes. Staccato notes are usually terminated by tongue contact, producing an exponential decrease in sound pressure with rates similar to those calculated from the bandwidths of the bore resonances: ∼400 dB s(-1). In all other cases, notes are stopped by decreasing P¯mouth. Notes played with different dynamics are qualitatively similar, but louder notes have larger P¯mouth and larger r.

  10. PEGylated PAMAM dendrimer-doxorubicin conjugate-hybridized gold nanorod for combined photothermal-chemotherapy.

    PubMed

    Li, Xiaojie; Takashima, Munenobu; Yuba, Eiji; Harada, Atsushi; Kono, Kenji

    2014-08-01

    We prepared pH-sensitive drug-dendrimer conjugate-hybridized gold nanorod as a promising platform for combined cancer photothermal-chemotherapy under in vitro and in vivo conditions. Poly(ethylene glycol)-attached PAMAM G4 dendrimers (PEG-PAMAM) were first covalently linked on the surface of mercaptohexadecanoic acid-functionalized gold nanorod (MHA-AuNR), with subsequent conjugation of anti-cancer drug doxorubicin (DOX) to dendrimer layer using an acid-labile-hydrazone linkage to afford PEG-DOX-PAMAM-AuNR particles. The particles with a high PEG-PAMAM dendrimer coverage density (0.28 per nm(2) AuNR) showed uniform sizes and excellent colloidal stability. In vitro drug release studies demonstrated that DOX released from PEG-DOX-PAMAM-AuNR was negligible under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. The efficient intracellular acid-triggered DOX release inside of lysosomes was confirmed using confocal laser scanning microscopy analysis. Furthermore, the combined photothermal-chemo treatment of cancer cells using PEG-DOX-PAMAM-AuNR for synergistic hyperthermia ablation and chemotherapy was demonstrated both in vitro and in vivo to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of PEG-DOX-PAMAM-AuNR particles for cancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Enalapril maleate orally disintegrating tablets: tableting and in vivo evaluation in hypertensive rats.

    PubMed

    Tawfeek, Hesham M; Faisal, Waleed; Soliman, Ghareb M

    2018-06-01

    The aim of this study was to develop orally disintegrating tablets (ODTs) for enalapril maleate (EnM) to facilitate its administration to the elderly or other patients having dysphagia. Compatibility between EnM and various excipients was studied using differential scanning calorimetry. ODTs of EnM were prepared by direct compression of EnM mixtures with various superdisintegrants. The tablets were evaluated for physical properties including drug content, hardness, friability, disintegration time, wetting time, and drug release. The antihypertensive effect of the optimum EnM ODTs was evaluated in vivo in hypertensive rats and compared with commercial EnM formulation. EnM ODTs had satisfactory results in terms of drug content and friability. Tablet wetting and disintegration were fast and dependent on the used superdisintegrant where croscarmellose showed the fastest wetting and disintegration time of ∼7 s. EnM release from the tablets was rapid where complete release was obtained in 10-15 min. Selected EnM ODTs rapidly and efficiently reduced the rat's blood pressure to its normal value within 1 h, compared with 4 h for EnM commercial formulation. These results confirm that EnM ODTs could find application in the management of hypertension in the elderly or other patients having dysphagia.

  12. 19 CFR 351.403 - Sales used in calculating normal value; transactions between affiliated parties.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Sales used in calculating normal value... ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Calculation of Export Price, Constructed Export Price, Fair Value, and Normal Value § 351.403 Sales used in calculating normal value...

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

    Wolfe, R.R.; Peters, E.J.; Klein, S.

    In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion were determined. The rate of appearance (R/sub a/) of free fatty acids (FFA) and glycerol were quantified by infusion of (1- TC)palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H2 YO dilution. In normal volunteers, the basal R/sub a/more » FFA and R/sub a/ glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting.« less

  14. Enlightenment about the new Architect-i2000 estradiol (Abbott Laboratories) immunoassay during in vitro fertilization.

    PubMed

    Taieb, Joëlle; Mendez Lozano, Daniel H; Benattar, Clarisse; Messaoudi, Chérif; Poüs, Christian

    2007-12-01

    We assessed a new estradiol (E2) immunoassay on the Architect-i2000 (Abbott Laboratories) for monitoring ovulation stimulation for IVF-ET and re-establishing clinical cut-off points. The method has been modified to improve E2 measurements especially at normal and low concentrations. E2 was determined for 552 samples, from 83 women, presenting normal follicular status and undergoing 100 cycles of IVF treatment. We assessed the value of this assay for down-regulation of E2 concentration limit using gonadoliberin-releasing hormone agonist (GnRHa), and monitoring of the ovarian hyperstimulation, expected range of E2 per mature follicle prior to the administration of exogenous hCG and day 3 concentration limit. We compared results with our routine method (E2-6II Advia-Centaur; Siemens-Diagnostics) for which decision-making values were known. Considering E2 concentrations obtained with the new Architect-i2000 assay for patients treated with GnRHa for 2 weeks, the cutoff-point for ovarian down-regulation should be set down at 110 pmol/L to maintain 100% of sensitivity. Considering day 3 concentration limit determination, results were not significantly different from those obtained with our routine method. The mean E2 values per mature follicle fell into the range generally expected. E2 determination with the new E2 Architect-i2000 assay could be used to monitor ovulation, in patients undergoing IVF-ET, in combination with transvaginal ultrasound.

  15. Quantifying biomass consumption and carbon release from the California Rim fire by integrating airborne LiDAR and Landsat OLI data.

    PubMed

    Garcia, Mariano; Saatchi, Sassan; Casas, Angeles; Koltunov, Alexander; Ustin, Susan; Ramirez, Carlos; Garcia-Gutierrez, Jorge; Balzter, Heiko

    2017-02-01

    Quantifying biomass consumption and carbon release is critical to understanding the role of fires in the carbon cycle and air quality. We present a methodology to estimate the biomass consumed and the carbon released by the California Rim fire by integrating postfire airborne LiDAR and multitemporal Landsat Operational Land Imager (OLI) imagery. First, a support vector regression (SVR) model was trained to estimate the aboveground biomass (AGB) from LiDAR-derived metrics over the unburned area. The selected model estimated AGB with an R 2 of 0.82 and RMSE of 59.98 Mg/ha. Second, LiDAR-based biomass estimates were extrapolated to the entire area before and after the fire, using Landsat OLI reflectance bands, Normalized Difference Infrared Index, and the elevation derived from LiDAR data. The extrapolation was performed using SVR models that resulted in R 2 of 0.73 and 0.79 and RMSE of 87.18 (Mg/ha) and 75.43 (Mg/ha) for the postfire and prefire images, respectively. After removing bias from the AGB extrapolations using a linear relationship between estimated and observed values, we estimated the biomass consumption from postfire LiDAR and prefire Landsat maps to be 6.58 ± 0.03 Tg (10 12  g), which translate into 12.06 ± 0.06 Tg CO2 e released to the atmosphere, equivalent to the annual emissions of 2.57 million cars.

  16. Naltrexone-loaded poly[La-(Glc-Leu)] polymeric microspheres for the treatment of alcohol dependence: in vitro characterization and in vivo biocompatibility assessment.

    PubMed

    Pagar, Kunal P; Vavia, Pradeep R

    2014-06-01

    The poly[La-(Glc-Leu)] copolymer was applied in the present investigation as polymeric carrier to fabricate naltrexone (NTX)-loaded poly[La-(Glc-Leu)] microspheres in the single emulsion solvent evaporation technique for the long-term treatment of alcohol dependence. Newly synthesized poly[La-(Glc-Leu)] copolymer exhibited diminished crystallanity, good biocompatibility and favorable biodegradability to be explored for drug delivery application. Scanning Electron Microscopy study revealed smooth and spherical-shaped NTX-loaded polymeric microspheres with a mean size of 10-90 µm. Influence of various decisive formulation variables such as amount of polymer, stabilizer concentration, homogenization speed, homogenization time, drug loading and organic-to-aqueous phase ratio on particle size, and entrapment efficiency was studied. Differential scanning calorimeter and X-ray diffractometry study confirmed the drug entrapment within polymer matrix into the microsphere environment. In vitro drug release showed the sustained drug release of formulation for the period of 28 d giving biphasic release pattern. Histological examination of NTX-loaded poly[La-(Glc-Leu)] microspheres injected intramuscularly into the thigh muscle of Wistar rats showed minimal inflammatory reaction, demonstrating that NTX-loaded microspheres were biocompatible. Insignificant increase in the serum creatine phosphokinase level (p < 0.05) as compared with the normal value revealed good muscle compatibility of the poly[La-(Glc-Leu)] microsphere system. Biocompatible nature and sustained drug-release action of poly[La-(Glc-Leu)] microspheres may have potential application in depot therapy.

  17. Quantifying biomass consumption and carbon release from the California Rim fire by integrating airborne LiDAR and Landsat OLI data

    PubMed Central

    Saatchi, Sassan; Casas, Angeles; Koltunov, Alexander; Ustin, Susan; Ramirez, Carlos; Garcia‐Gutierrez, Jorge; Balzter, Heiko

    2017-01-01

    Abstract Quantifying biomass consumption and carbon release is critical to understanding the role of fires in the carbon cycle and air quality. We present a methodology to estimate the biomass consumed and the carbon released by the California Rim fire by integrating postfire airborne LiDAR and multitemporal Landsat Operational Land Imager (OLI) imagery. First, a support vector regression (SVR) model was trained to estimate the aboveground biomass (AGB) from LiDAR‐derived metrics over the unburned area. The selected model estimated AGB with an R 2 of 0.82 and RMSE of 59.98 Mg/ha. Second, LiDAR‐based biomass estimates were extrapolated to the entire area before and after the fire, using Landsat OLI reflectance bands, Normalized Difference Infrared Index, and the elevation derived from LiDAR data. The extrapolation was performed using SVR models that resulted in R 2 of 0.73 and 0.79 and RMSE of 87.18 (Mg/ha) and 75.43 (Mg/ha) for the postfire and prefire images, respectively. After removing bias from the AGB extrapolations using a linear relationship between estimated and observed values, we estimated the biomass consumption from postfire LiDAR and prefire Landsat maps to be 6.58 ± 0.03 Tg (1012 g), which translate into 12.06 ± 0.06 Tg CO2e released to the atmosphere, equivalent to the annual emissions of 2.57 million cars. PMID:28405539

  18. Numerical investigation of the effect of delaminations on fracture characteristics of glare

    NASA Astrophysics Data System (ADS)

    Bhat, Sunil; Narayanan, S.

    2013-10-01

    A finite element examination of the effect of delaminations on fracture characteristics of fibre metal laminate (Glare), by comparing energy release rates of normal cracks in laminates with and without delaminations, is presented in the paper. Glare comprising thin cracked 2024-T3 aerospace aluminum alloy layers alternately bonded with E-glass fibre based composite prepregs is considered for the analysis. Delaminations are modeled with interface cohesive elements. Energy release rates of normal cracks in laminates with delaminations are found to be higher than those in the laminates without delaminations.

  19. Prolonged cytotoxic effect of colchicine released from biodegradable microspheres.

    PubMed

    Muvaffak, Asli; Gurhan, Ismet; Hasirci, Nesrin

    2004-11-15

    One the main problems of cancer chemotherapy is the unwanted damage to normal cells caused by the high toxicities of anticancer drugs. Any system of controlled drug delivery that would reduce the total amount of drug required, and thus reduce the side effects, would potentially help to improve chemotherapy. In this respect, biodegradable gelatin microspheres were prepared by water/oil emulsion polymerization and by crosslinking with glutaraldehyde (GTA) as the drug-carrier system. Microspheres were loaded with colchicine, a model antimitotic drug, which was frequently used as an antimitotic agent in cancer research involving cell cultures. Microsphere sizes, swelling and degradation properties, drug-release kinetics, and cytotoxities were studied. Swelling characteristics of microspheres changed upon changing GTA concentration. A decrease in swelling values was recorded as GTA crosslink density was increased. In vitro drug release in PBS (0.01M, pH 7.4) showed rapid colchicine release up to approximately 83% (at t = 92 h) for microspheres with low GTA (0.05% v/v), whereas a slower release profile (only approximately 39%) was obtained for microspheres with high GTA (0.50% v/v) content, for the same period. Cytotoxicity tests with MCF-7, HeLa and H-82 cancer cell lines showed that free colchicine was very toxic, showing an approximately 100% lethal effect in both HeLa and H-82 cell lines and more than 50% decrease in viability in MCF-7 cells in 4 days. Indeed, entrapped colchicine indicated similar initial high toxic effect on cell viability in MCF-7 cell line and this effect became more dominant as colchicine continued to be released from microspheres in the same period. In conclusion, the control of the release rate of colchicine from gelatin microspheres was achieved under in vitro conditions by gelatin through the alteration of crosslinking conditions. Indeed, the results suggested the potential application of gelatin microspheres crosslinked with GTA as a sustained drug-delivery system for anticancer drugs for local chemotherapy administrations. (c) 2004 Wiley Periodicals, Inc.

  20. Physiological response of some economically important freshwater salmonids to catch-and-release fishing

    USGS Publications Warehouse

    Wedemeyer, G.A.; Wydoski, R.S.

    2008-01-01

    Catch-and-release fishing regulations are widely used by fishery resource managers to maintain both the quantity and quality of sport fish populations. We evaluated blood chemistry disturbances in wild brook trout Salvelinus fontinalis, brown trout Salmo trutta, cutthroat trout Oncorhynchus clarkii, and Arctic grayling Thymallus arcticus that had been hooked and played for 1-5 min in waters of the intermountain western United States. A hatchery stock of brown trout was included for comparison. To assess time needed for recovery, additional test groups were played for 5 min and then released into net-pens, where they were held for up to 72 h. The osmoregulatory and metabolic disturbances associated with catch-and-release fishing under the conditions we tested were minimal and judged to be well within normal physiological tolerance limits. In fish that were held for recovery, the blood chemistry alterations that did occur appeared to be related to stress from confinement in the net-pens. Our results confirm the results of previous studies, showing that prerelease air exposure and handling cause more physiological stress than does either hooking per se or playing time. Fishery managers must be aware of the differences in the perceptions, attitudes, and values of different societal groups, some of which feel that catch-and-release fishing should be banned because it is cruel to the animals. On the basis of brain anatomy, it seems highly unlikely that fish experience pain in the same manner as humans experience it, because fish lack a neocortex, the brain structure that enables the sensation of pain in higher vertebrates. However, independent of the neurobiological argument, our results indicate that under conditions similar to those tested, fish subjected to catch and release are neither suffering nor particularly stressed. Improved education programs about the relatively benign physiological effects of catch-and-release fishing as a fishery management practice would be beneficial to anglers and the nonfishing public alike.

  1. Restitution of defective glucose-stimulated insulin secretion in diabetic GK rat by acetylcholine uncovers paradoxical stimulatory effect of beta-cell muscarinic receptor activation on cAMP production.

    PubMed

    Dolz, Manuel; Bailbé, Danielle; Giroix, Marie-Hélène; Calderari, Sophie; Gangnerau, Marie-Noelle; Serradas, Patricia; Rickenbach, Katharina; Irminger, Jean-Claude; Portha, Bernard

    2005-11-01

    Because acetylcholine (ACh) is a recognized potentiator of glucose-stimulated insulin release in the normal beta-cell, we have studied ACh's effect on islets of the Goto-Kakizaki (GK) rat, a spontaneous model of type 2 diabetes. We first verified that ACh was able to restore the insulin secretory glucose competence of the GK beta-cell. Then, we demonstrated that in GK islets 1) ACh elicited a first-phase insulin release at low glucose, whereas it had no effect in Wistar; 2) total phospholipase C activity, ACh-induced inositol phosphate production, and intracellular free calcium concentration ([Ca2+]i) elevation were normal; 3) ACh triggered insulin release, even in the presence of thapsigargin, which induced a reduction of the ACh-induced [Ca2+]i response (suggesting that ACh produces amplification signals that augment the efficacy of elevated [Ca2+]i on GK exocytosis); 4) inhibition of protein kinase C did not affect [Ca2+]i nor the insulin release responses to ACh; and 5) inhibition of cAMP-dependent protein kinases (PKAs), adenylyl cyclases, or cAMP generation, while not affecting the [Ca2+]i response, significantly lowered the insulinotropic response to ACh (at low and high glucose). In conclusion, ACh acts mainly through activation of the cAMP/PKA pathway to potently enhance Ca2+-stimulated insulin release in the GK beta-cell and, in doing so, normalizes its defective glucose responsiveness.

  2. A systematic investigation into b values prior to coming large earthquakes

    NASA Astrophysics Data System (ADS)

    Nanjo, K.; Yoshida, A.

    2017-12-01

    The Gutenberg-Richter law for frequency-magnitude distribution of earthquakes is now well established in seismology. The b value, the slope of the distribution, is supposed to reflect heterogeneity of seismogenic region (e.g. Mogi 1962) and development of interplate coupling in subduction zone (e.g. Nanjo et al., 2012; Tormann et al. 2015). In the laboratory as well as in the Earth's crust, the b value is known to be inversely dependent on differential stresses (Scholz 1968, 2015). In this context, the b value could serve as a stress meter to help locate asperities, the highly-stressed patches, in fault planes where large rupture energy is released (e.g. Schorlemmer & Wiemer 2005). However, it still remains uncertain whether the b values of events prior to coming large earthquakes are always low significantly. To clarify this issue, we conducted a systematic investigation into b values prior to large earthquakes in the Japanese Mainland. Since no physical definition of mainshock, foreshock, and aftershock is known, we simply investigated b values of the events with magnitudes larger than the lower-cutoff magnitude, Mc, prior to earthquakes equal to or larger than a threshold magnitude, Mth, where Mth>Mc. Schorlemmer et al. (2005) showed that the b value for different fault types differs significantly, which is supposed to reflect the feature that the fracture stress depends on fault types. Therefore, we classified fault motions into normal, strike-slip, and thrust types based on the mechanism solution of earthquakes, and computed b values of events associated with each fault motion separately. We found that the target events (M≥Mth) and the events that occurred prior to the target events both show a common systematic change in b: normal faulting events have the highest b values, thrust events the lowest and strike-slip events intermediate values. Moreover, we found that the b values for the prior events (M≥Mc) are significantly lower than the b values for the target events (M≥Mth), though their b values change somewhat depending on the choice of the parameter values to define the target events (M≥Mth) and the prior events (M≥Mc). This finding indicates that the b value could be used as an effective index for foreseeing occurrence of large earthquakes, if the parameter values are well-tuned.

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

    Pirhonen, P.

    Life-cycle assessment is usually based on regular discharges that occur at a more or less constant rate. Nevertheless, the more factors that are taken into account in the LCA the better picture it gives on the environmental aspects of a product. In this study an approach to incorporate accidental releases into a products` life-cycle assessment was developed. In this approach accidental releases are divided into two categories. The first category consists of those unplanned releases which occur with a predicted level and frequency. Due to the high frequency and small release size at a time, these accidental releases can bemore » compared to continuous emissions. Their global impacts are studied in this approach. Accidental releases of the second category are sudden, unplanned releases caused by exceptional situations, e.g. technical failure, action error or disturbances in process conditions. These releases have a singular character and local impacts are typical of them. As far as the accidental releases of the second category are concerned, the approach introduced in this study results in a risk value for every stage of a life-cycle, the sum of which is a risk value for the whole life-cycle. Risk value is based on occurrence frequencies of incidents and potential environmental damage caused by releases. Risk value illustrates the level of potential damage caused by accidental releases related to the system under study and is meant to be used for comparison of these levels of two different products. It can also be used to compare the risk levels of different stages of the life-cycle. An approach was illustrated using petrol as an example product. The whole life-cycle of petrol from crude oil production to the consumption of petrol was studied.« less

  4. UNCLASSIFIED TPBAR RELEASES, INCLUDING TRITIUM TTQP-1-091 Rev 14

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

    Gruel, Robert L.; Love, Edward F.; Thornhill, Cheryl K.

    This document provides a listing of unclassified tritium release values that should be assumed for unclassified analysis. Much of the information is brought forth from the related documents listed in Section 5.0 to provide a single-source listing of unclassified release values. This information has been updated based on current design analysis and available experimental data.

  5. Puberty, statural growth, and growth hormone release in children with cerebral palsy

    PubMed Central

    Kuperminc, Michelle N.; Gurka, Matthew J.; Houlihan, Christine M.; Henderson, Richard C.; Roemmich, James N.; Rogol, Alan D.

    2010-01-01

    Objective Children with cerebral palsy (CP) are smaller than normally growing children.. The association between the growth hormone (GH) axis and growth in children with CP during puberty is unknown. We compared growth and markers of the GH axis in pre-pubertal and pubertal children with moderate to severe CP and without CP over a three-year period. Study design Twenty children with CP, ages 6–18, Gross Motor Function Classification System levels III–V, were compared to a group of sixty-three normally growing children of similar age. Anthropometry, Tanner stage, bone age, and laboratory analyses were performed every six months for three years. Laboratory values included spontaneous overnight GH release, fasting IGF-1 and IGFBP-3. Repeated measures models were used to evaluate interactions among Tanner stage and group (children with CP vs. reference children), taking into account gender, age, and nutritional status. Results Children with CP grew more slowly than those without CP at all Tanner stages (p<0.01). Patterns of IGF-1 and GH secretion in children with CP were similar to those of the reference group; however, the concentrations of IGF-1 (p<0.01) and GH (p<0.01) were lower in girls with CP, with a similar trend for boys (p=0.10 and 0.14, respectively). Conclusions Diminished circulating IGF-1 and GH concentrations may explain the differences in growth between the two groups. PMID:20216931

  6. Mechanisms behind Post-Thyroidectomy Hypocalcemia: Interplay of Calcitonin, Parathormone, and Albumin-A Prospective Study.

    PubMed

    Chisthi, Meer M; Nair, Rakhi S; Kuttanchettiyar, Krishnakumar G; Yadev, Induprabha

    2017-08-01

    Hypocalcemia after thyroidectomy is attributed to injury or ischemia to parathyroid glands. Transient hypocalcemia in thyroidectomy when parathyroids are preserved is not adequately explained. Release of calcitonin and hypoalbuminemia are two proposed reasons. Primary objective of this study was to find the change in calcitonin in the postoperative period after total thyroidectomy. Secondarily, hypocalcemia and its correlation with calcitonin, albumin, and parathormone were also studied. This Cohort study was carried out at the general surgical department of a tertiary level teaching institution from April 2015 to December 2015. One hundred adult patients undergoing total thyroidectomy, with at least three parathyroids being preserved were included. Changes in calcium, calcitonin, albumin, and parathormone were studied based on preoperative levels and the values at 1, 6, 24, and 48 hr after surgery. Calcitonin increased at one hour after thyroidectomy and fell below preoperative levels subsequently. Parathormone showed a mild rise at one hour and normalized subsequently. Total calcium, corrected calcium, and albumin showed decline at one hour and recovered gradually over the next two days. At preoperative level, calcium had significant correlation with parathormone alone. Calcium levels at one hour had significant correlation with calcitonin. All post-operative calcium levels had significant correlation with parathormone and the number of parathyroids preserved in situ without auto-transplantation. There is significant hypocalcemia within the first 24 hr after thyroidectomy, caused by calcitonin release and hypoalbuminemia. Preservation of maximum number of parathyroids in-situ can counter and normalize this hypocalcemia.

  7. Research on a Sudden Explosion and its Environmental Impact

    NASA Astrophysics Data System (ADS)

    Ye, Maosheng; Ma, Hui; Ni, Qingwei

    2017-12-01

    A sudden blast was chosen as the studied topic. Also, one computer based virtual experimentation was used to estimate the dimensional impact of initial pollutant plume from blasts. Self-made method using Mathcad code was used to generate the output for the period of the first tenth of a second (1deci-second) to 1minute (60s) of the blast at the point source. It also depicted long-range air pollution travel within the first 1 to 10 minutes. In the case study, it assumed an average directional diffusivity of 1720 m2s-1 which is about 25 per cent of the average generated speed of common explosives. The newly developed model revealed a plume cloud impact of 6.8×107µgm-3 in the first 1millisecond (0.01s) which decayed suddenly to a value of 1.7×107µgm-3 in the first 1decisecond (0.1s). The impact concentration at the point source by the end of the first second (1.0s) was 3.2×105µgm-3 which implied a 99.5% sudden decay when compared to 0.01s concentration value at the emission point source. Computerized experiments observed that air pollutants release from explosives/blasts were dispersed into the atmosphere in the first few seconds by forceful injection instead of by gradual dispersion as is the case with normal air pollutants plume releases.

  8. Long-term physiological effects of enhanced O/sub 2/ release by inositol hexaphosphate-loaded erythrocytes

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

    Teisseire, B.; Ropars, C.; Villereal, M.C.

    1987-10-01

    A continuous lysing and resealing procedure with erythrocytes permitted incorporation in these cells of inositol hexaphosphate (InsP/sub 6/), a strong allosteric effector of Hb. This leads to significant rightward shifts of the HbO/sub 2/ dissociation curves with in vitro P/sub 50/, values increasing from 32.2 +/- 1.8 torr for control erythrocytes to 86 +/- 60 torr. The shape of the dissociation curve was still sigmoidal, although the Hill coefficient was decreased. The life span of InsP/sub 6/-loaded erythrocytes equaled that of control erythrocytes. Erythrocyte-survival studies were done using /sub 51/Cr labeling of cells. The long-term physiological effects of the InsP/submore » 6/-loaded erythrocytes on piglets were increased O/sub 2/ release and reduced cardiac output. The reduced O/sub 2/ affinity of the InsP/sub 6/-loaded erythrocytes was still effective 20 days after transfusion in awake piglets. The electrolyte concentration appeared stable over the 5-day observation period except for a transient, but significant, hyperkalemia immediately after transfusion. The reductions in the O/sub 2/ affinity of Hb reported here are large compared with previously reported values. Introduction of InsP/sub 6/ into viable erythrocytes improves tissue oxygenation when, for any reason, normal blood flow is impaired.« less

  9. Mechanical energy storage device for hip disarticulation

    NASA Technical Reports Server (NTRS)

    Vallotton, W. C. (Inventor)

    1977-01-01

    An artificial leg including a trunk socket, a thigh section hingedly coupled to the trunk socket, a leg section hingedly coupled to the thigh section and a foot section hingedly coupled to the leg section is outlined. A mechanical energy storage device is operatively associated with the artificial leg for storage and release of energy during the normal walking stride of the user. Energy is stored in the mechanical energy storage device during a weight-bearing phase of the walking stride when the user's weight is on the artificial leg. Energy is released during a phase of the normal walking stride, when the user's weight is removed from the artificial leg. The stored energy is released from the energy storage device to pivot the thigh section forwardly about the hinged coupling to the trunk socket.

  10. The sensory features of a food cue influence its ability to act as an incentive stimulus and evoke dopamine release in the nucleus accumbens core

    PubMed Central

    Bryan, Myranda A.; Popov, Pavlo; Scarff, Raymond; Carter, Cody; Wright, Erin; Aragona, Brandon J.; Robinson, Terry E.

    2016-01-01

    The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual information, resulting in CRs that vary both within and between individuals. For example, CRs include approach to the lever-CS itself (rats that “sign-track”; ST), approach to the location of reward delivery (rats that “goal-track”; GT), or an “intermediate” combination of these behaviors. We found that the multimodal sensory features of the lever-CS were important to the development and expression of sign-tracking. When the lever-CS was covered, and thus could only be heard moving, STs not only continued to approach the lever location but also started to approach the food cup during the CS period. While still predictive of reward, the auditory component of the lever-CS was a much weaker conditioned reinforcer than the visible lever-CS. This plasticity in behavioral responding observed in STs closely resembled behaviors normally seen in rats classified as “intermediates.” Furthermore, the ability of both the lever-CS and the reward-delivery to evoke dopamine release in the nucleus accumbens was also altered by covering the lever—dopamine signaling in STs resembled neurotransmission observed in rats that normally only GT. These data suggest that while the visible lever-CS was attractive, wanted, and had incentive value for STs, when presented in isolation, the auditory component of the cue was simply predictive of reward, lacking incentive salience. Therefore, the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility. PMID:27918279

  11. Hepatotoxicity associated with metformin therapy in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease.

    PubMed

    Cone, Catherine J; Bachyrycz, Amy M; Murata, Glen H

    2010-10-01

    To report a case of idiosyncratic hepatotoxicity associated with metformin in the treatment of type 2 diabetes with nonalcoholic fatty liver disease (NAFLD). A 61-year-old obese man presented with jaundice, nausea, fatigue, and an unintentional weight loss 2 weeks following initiation of metformin. Laboratory findings revealed aminotransferase values 10-15 times the upper limit of normal. Potential causative agents, including metformin, simvastatin, and Niaspan (extended-release niacin), were discontinued. Two months later, the patient's signs and symptoms had resolved and aminotransferase values returned to normal. An objective causality assessment revealed that the adverse reaction was probably associated with metformin. Since numerous medications and disease states can cause abnormalities in liver enzymes, it is important for providers to be able to distinguish the cause(s) and take appropriate actions. This can take a great deal of time and effort in patients with multiple medications and comorbidities. In this patient's case, viral hepatitis, worsening NAFLD, and the concomitant drugs were highly suspected. As hydroxymethylglutaryl coenzyme A reductase inhibitors offer substantial cardiovascular benefits and as metformin is a first-line agent in helping to lower blood glucose concentrations and to normalize the metabolic profile in type 2 diabetes, reintroduction of metformin and simvastatin would likely be beneficial. This is a case report of metformin-induced hepatotoxicity. As the prevalence of type 2 diabetes and subsequent metabolic effects increases in the US, metformin use will likewise increase. As potential for increased idiosyncratic hepatotoxicity associated with metformin use is likely to occur, clinicians should be vigilant.

  12. Unexpectedly increased anorexigenic postprandial responses of PYY and GLP-1 to fast ice cream consumption in adult patients with Prader-Willi syndrome.

    PubMed

    Rigamonti, A E; Bini, S; Grugni, G; Agosti, F; De Col, A; Mallone, M; Cella, S G; Sartorio, A

    2014-10-01

    The effect of eating rate on the release of anorexigenic gut peptides in Prader-Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far. Postprandial PYY and GLP-1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age-matched patients with simple obesity and normal-weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety. Fast ice cream consumption stimulated GLP-1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP-1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP-1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding. Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age-matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions. © 2013 John Wiley & Sons Ltd.

  13. Characteristics of CO2 release from forest soil in the mountains near Beijing.

    PubMed

    Sun, Xiang Yang; Gao, Cheng Da; Zhang, Lin; Li, Su Yan; Qiao, Yong

    2011-04-01

    CO2 release from forest soil is a key driver of carbon cycling between the soil and atmosphere ecosystem. The rate of CO2 released from soil was measured in three forest stands (in the mountainous region near Beijing, China) by the alkaline absorption method from 2004 to 2006. The rate of CO2 released did not differ among the three stands. The CO2 release rate ranged from - 341 to 1,193 mg m(-2) h(-1), and the mean value over all three forests and sampling times was 286 mg m(-2) h(-1). CO2 release was positively correlated with soil water content and the soil temperature. Diurnally, CO2 release was higher in the day than at night. Seasonally, CO2 release was highest in early autumn and lowest in winter; in winter, negative values of CO2 release suggested that CO2 was absorbed by soil.

  14. Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

    PubMed

    Bodel, P; Ralph, P; Wenc, K; Long, J C

    1980-02-01

    Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous pyrogen from the two cell lines was similar and closely resembled that produced by normal human monocytes in antigenic properties as well as heat and pronase sensitivity. The Hodgkin's disease and histiocytic lymphoma cell lines do not require specific stimulation for the production of endogenous pyrogen suggesting that the mechanism of pyrogen release by neoplastic macrophage-related cells differs from that of normal phagocytic cells. The tumor-associated fever in some patients with malignant lymphoma may be caused by a release of endogenous pyrogen by proliferating neoplastic cells.

  15. Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

    PubMed Central

    Bodel, P; Ralph, P; Wenc, K; Long, J C

    1980-01-01

    Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous pyrogen from the two cell lines was similar and closely resembled that produced by normal human monocytes in antigenic properties as well as heat and pronase sensitivity. The Hodgkin's disease and histiocytic lymphoma cell lines do not require specific stimulation for the production of endogenous pyrogen suggesting that the mechanism of pyrogen release by neoplastic macrophage-related cells differs from that of normal phagocytic cells. The tumor-associated fever in some patients with malignant lymphoma may be caused by a release of endogenous pyrogen by proliferating neoplastic cells. PMID:6985918

  16. 19 CFR 351.406 - Calculation of normal value if sales are made at less than cost of production.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Calculation of normal value if sales are made at less than cost of production. 351.406 Section 351.406 Customs Duties INTERNATIONAL TRADE ADMINISTRATION... Price, Fair Value, and Normal Value § 351.406 Calculation of normal value if sales are made at less than...

  17. Estimation of value at risk and conditional value at risk using normal mixture distributions model

    NASA Astrophysics Data System (ADS)

    Kamaruzzaman, Zetty Ain; Isa, Zaidi

    2013-04-01

    Normal mixture distributions model has been successfully applied in financial time series analysis. In this paper, we estimate the return distribution, value at risk (VaR) and conditional value at risk (CVaR) for monthly and weekly rates of returns for FTSE Bursa Malaysia Kuala Lumpur Composite Index (FBMKLCI) from July 1990 until July 2010 using the two component univariate normal mixture distributions model. First, we present the application of normal mixture distributions model in empirical finance where we fit our real data. Second, we present the application of normal mixture distributions model in risk analysis where we apply the normal mixture distributions model to evaluate the value at risk (VaR) and conditional value at risk (CVaR) with model validation for both risk measures. The empirical results provide evidence that using the two components normal mixture distributions model can fit the data well and can perform better in estimating value at risk (VaR) and conditional value at risk (CVaR) where it can capture the stylized facts of non-normality and leptokurtosis in returns distribution.

  18. Reintroduction medicine: whooping cranes in Wisconsin.

    PubMed

    Keller, Dominique L; Hartup, Barry K

    2013-01-01

    This paper presents veterinary management strategies and diagnostic findings in the reintroduction of the endangered whooping crane (Grus americana). Between 2005 and 2010, 63 (27 male, 36 female) hatchling whooping cranes were assigned to a reintroduction project involving autumn release of costume-reared chicks in Wisconsin. Veterinary care included preventive measures and comprehensive pre-release evaluations to improve fitness and reduce translocation of potential disease agents to native habitats. A total of 44 clinically normal birds were released (70% of assigned individuals). Cases of morbidity were classified according to primary body system affected. Musculoskeletal disorders were described in 57 birds (90%); five birds were removed from the project prior to release (8%), all for abnormalities that prevented normal function. Fourteen birds died or were euthanized prior to release (22%); pre-release mortality was attributed to developmental abnormality, predation, trauma or infectious disease. Chronic respiratory aspergillosis, diagnosed in seven birds (11%), was the most common infectious disease of concern. Predation and trauma were primary causes of post-release mortality; no evidence of infectious disease of captive origin was detected in the study population by the end of 2010. The assessment of data accumulated by this project helped to outline successful health management strategies, as well as identify and mitigate ongoing risks to captive whooping cranes that impede reintroduction efforts and achieving management goals for species recovery. © 2013 Wiley Periodicals, Inc.

  19. Mice Lacking Pannexin 1 Release ATP and Respond Normally to All Taste Qualities.

    PubMed

    Vandenbeuch, Aurelie; Anderson, Catherine B; Kinnamon, Sue C

    2015-09-01

    Adenosine triphosphate (ATP) is required for the transmission of all taste qualities from taste cells to afferent nerve fibers. ATP is released from Type II taste cells by a nonvesicular mechanism and activates purinergic receptors containing P2X2 and P2X3 on nerve fibers. Several ATP release channels are expressed in taste cells including CALHM1, Pannexin 1, Connexin 30, and Connexin 43, but whether all are involved in ATP release is not clear. We have used a global Pannexin 1 knock out (Panx1 KO) mouse in a series of in vitro and in vivo experiments. Our results confirm that Panx1 channels are absent in taste buds of the knockout mice and that other known ATP release channels are not upregulated. Using a luciferin/luciferase assay, we show that circumvallate taste buds from Panx1 KO mice normally release ATP upon taste stimulation compared with wild type (WT) mice. Gustatory nerve recordings in response to various tastants applied to the tongue and brief-access behavioral testing with SC45647 also show no difference between Panx1 KO and WT. These results confirm that Panx1 is not required for the taste evoked release of ATP or for neural and behavioral responses to taste stimuli. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Serum pro-gastrin-releasing peptide (31-98) in benign prostatic hyperplasia and prostatic carcinoma.

    PubMed

    Nagakawa, Osamu; Furuya, Yuzo; Fujiuchi, Yasuyoshi; Fuse, Hideki

    2002-09-01

    To clarify whether serum levels of pro-gastrin-releasing peptide (ProGRP) (31-98) could be a useful marker in patients with prostatic carcinoma. GRP is produced and secreted by prostatic neuroendocrine cells. Serum levels of ProGRP(31-98) were measured by enzyme-linked immunosorbent assay in 20 patients with benign prostatic hyperplasia and 107 patients with prostatic carcinoma. The mean serum levels of ProGRP(31-98) in patients with distant metastasis and hormone-resistant prostate cancer were significantly elevated compared with those in patients with organ-confined disease. Significantly elevated levels of ProGRP(31-98) were detected in 9 patients with prostatic carcinoma before any treatment. During hormone-resistant prostate cancer progression, ProGRP(31-98) levels were elevated in 9 patients (23%). Of the 9 patients with Stage D3 and elevated serum ProGRP, 4 had a normal serum prostate-specific antigen level. ProGRP may be a potential tumor marker for prostate cancer. Additional studies in large groups of patients are needed to define the clinical value of ProGRP.

  1. The interaction between tropomyosin-related kinase B receptors and presynaptic muscarinic receptors modulates transmitter release in adult rodent motor nerve terminals.

    PubMed

    Garcia, Neus; Tomàs, Marta; Santafé, Manel M; Besalduch, Nuria; Lanuza, Maria A; Tomàs, Josep

    2010-12-08

    The neurotrophin brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and the receptors tropomyosin-related kinase B (trkB) and p75(NTR) are present in the nerve terminals on the neuromuscular junctions (NMJs) of the levator auris longus muscle of the adult mouse. Exogenously added BDNF or NT-4 increased evoked ACh release after 3 h. This presynaptic effect (the size of the spontaneous potentials is not affected) is specific because it is not produced by neurotrophin-3 (NT-3) and is prevented by preincubation with trkB-IgG chimera or by pharmacological block of trkB [K-252a (C₂₇H₂₁N₃O₅)] or p75(NTR) [Pep5 (C₈₆H₁₁₁N₂₅O₁₉S₂] signaling. The effect of BDNF depends on the M₁ and M₂ muscarinic acetylcholine autoreceptors (mAChRs) because it is prevented by atropine, pirenzepine and methoctramine. We found that K-252a incubation reduces ACh release (~50%) in a short time (1 h), but the p75(NTR) signaling inhibitor Pep5 does not have this effect. The specificity of the K-252a blocking effect on trkB was confirmed with the anti-trkB antibody 47/trkB, which reduces evoked ACh release, like K-252a, whereas the nonpermeant tyrosine kinase blocker K-252b does not. Neither does incubation with the fusion protein trkB-IgG (to chelate endogenous BDNF/NT-4), anti-BDNF or anti-NT-4 change ACh release. Thus, the trkB receptor normally seems to be coupled to ACh release when there is no short-term local effect of neurotrophins at the NMJ. The normal function of the mAChR mechanism is a permissive prerequisite for the trkB pathway to couple to ACh release. Reciprocally, the normal function of trkB modulates M₁- and M₂-subtype muscarinic pathways.

  2. Early Recovery of an Eastern Sierra Nevada Riparian System After 40 Years of Stream Diversion

    Treesearch

    Julie C. Stromberg; Duncan T. Patten

    1989-01-01

    Rush Creek, which feeds Mono Lake, has been diverted below Grant Lake, totally or in part, for over 40 years. In the early 1980's, because of above normal snow packs, runoff was released into the creek. Minimum flow releases have also been established. The riparian vegetation has responded to these releases. In a few areas, riparian trees and shrubs (e.g., black...

  3. Kinetics of Germination of Individual Spores of Geobacillus stearothermophilus as Measured by Raman Spectroscopy and Differential Interference Contrast Microscopy

    PubMed Central

    Zhou, Tingting; Dong, Zhiyang; Setlow, Peter; Li, Yong-qing

    2013-01-01

    Geobacillus stearothermophilus is a gram-positive, thermophilic bacterium, spores of which are very heat resistant. Raman spectroscopy and differential interference contrast microscopy were used to monitor the kinetics of germination of individual spores of G. stearothermophilus at different temperatures, and major conclusions from this work were as follows. 1) The CaDPA level of individual G. stearothermophilus spores was similar to that of Bacillus spores. However, the Raman spectra of protein amide bands suggested there are differences in protein structure in spores of G. stearothermophilus and Bacillus species. 2) During nutrient germination of G. stearothermophilus spores, CaDPA was released beginning after a lag time (T lag) between addition of nutrient germinants and initiation of CaDPA release. CaDPA release was complete at T release, and ΔT release (T release – T lag) was 1–2 min. 3) Activation by heat or sodium nitrite was essential for efficient nutrient germination of G. stearothermophilus spores, primarily by decreasing T lag values. 4) Values of T lag and T release were heterogeneous among individual spores, but ΔT release values were relatively constant. 5) Temperature had major effects on nutrient germination of G. stearothermophilus spores, as at temperatures below 65°C, average T lag values increased significantly. 6) G. stearothermophilus spore germination with exogenous CaDPA or dodecylamine was fastest at 65°C, with longer Tlag values at lower temperatures. 7) Decoating of G. stearothermophilus spores slowed nutrient germination slightly and CaDPA germination significantly, but increased dodecylamine germination markedly. These results indicate that the dynamics and heterogeneity of the germination of individual G. stearothermophilus spores are generally similar to that of Bacillus species. PMID:24058645

  4. An Exclusion Zone for Ca2+ Channels around Docked Vesicles Explains Release Control by Multiple Channels at a CNS Synapse

    PubMed Central

    Keller, Daniel; Babai, Norbert; Kochubey, Olexiy; Han, Yunyun; Markram, Henry; Schürmann, Felix; Schneggenburger, Ralf

    2015-01-01

    The spatial arrangement of Ca2+ channels and vesicles remains unknown for most CNS synapses, despite of the crucial importance of this geometrical parameter for the Ca2+ control of transmitter release. At a large model synapse, the calyx of Held, transmitter release is controlled by several Ca2+ channels in a "domain overlap" mode, at least in young animals. To study the geometrical constraints of Ca2+ channel placement in domain overlap control of release, we used stochastic MCell modelling, at active zones for which the position of docked vesicles was derived from electron microscopy (EM). We found that random placement of Ca2+ channels was unable to produce high slope values between release and presynaptic Ca2+ entry, a hallmark of domain overlap, and yielded excessively large release probabilities. The simple assumption that Ca2+ channels can be located anywhere at active zones, except below a critical distance of ~ 30 nm away from docked vesicles ("exclusion zone"), rescued high slope values and low release probabilities. Alternatively, high slope values can also be obtained by placing all Ca2+ channels into a single supercluster, which however results in significantly higher heterogeneity of release probabilities. We also show experimentally that high slope values, and the sensitivity to the slow Ca2+ chelator EGTA-AM, are maintained with developmental maturation of the calyx synapse. Taken together, domain overlap control of release represents a highly organized active zone architecture in which Ca2+ channels must obey a certain distance to docked vesicles. Furthermore, domain overlap can be employed by near-mature, fast-releasing synapses. PMID:25951120

  5. Conceptuation, formulation and evaluation of sustained release floating tablets of captopril compression coated with gastric dispersible hydrochlorothiazide using 23 factorial design

    PubMed Central

    Sirisha, Pathuri Lakshmi; Babu, Govada Kishore; Babu, Puttagunta Srinivasa

    2014-01-01

    Ambulatory blood pressure monitoring is regarded as the gold standard for hypertensive therapy in non-dipping hypertension patients. A novel compression coated formulation of captopril and hydrochlorothiazide (HCTZ) was developed in order to improve the efficacy of antihypertensive therapy considering the half-life of both drugs. The synergistic action using combination therapy can be effectively achieved by sustained release captopril (t1/2= 2.5 h) and fast releasing HCTZ (average t1/2= 9.5 h). The sustained release floating tablets of captopril were prepared by using 23 factorial design by employing three polymers i.e., ethyl cellulose (EC), carbopol and xanthan gum at two levels. The formulations (CF1-CF8) were optimized using analysis of variance for two response variables, buoyancy and T50%. Among the three polymers employed, the coefficients and P values for the response variable buoyancy and T50% using EC were found to be 3.824, 0.028 and 0.0196, 0.046 respectively. From the coefficients and P values for the two response variables, formulation CF2 was optimized, which contains EC polymer alone at a high level. The CF2 formulation was further compression coated with optimized gastric dispersible HCTZ layer (HF9). The compression coated tablet was further evaluated using drug release kinetics. The Q value of HCTZ layer is achieved within 20 min following first order release whereas the Q value of captopril was obtained at 6.5 h following Higuchi model, from which it is proved that rapid release HCTZ and slow release of captopril is achieved. The mechanism of drug release was analyzed using Peppas equation, which showed an n >0.90 confirming case II transportation mechanism for drug release. PMID:25006552

  6. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

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

    Romshe, C.A.; Zipf, W.B.; Miser, A.

    1984-02-01

    We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significantmore » differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.« less

  7. A Demonstration of Sympathetic Cotransmission

    ERIC Educational Resources Information Center

    Johnson, Christopher D.

    2010-01-01

    Currently, most undergraduate textbooks that cover the autonomic nervous system retain the concept that autonomic nerves release either acetylcholine or norepinephrine. However, in recent years, a large volume of research has superseded this concept with one in which autonomic nerves normally release at least one cotransmitter along with a…

  8. Time analysis for optimization of radiology workflow in conventional radiology during RIS-PACS-integration

    NASA Astrophysics Data System (ADS)

    Falkensammer, Peter; Soegner, Peter I.; zur Nedden, Dieter

    2002-05-01

    The integration of RIS-PACS systems in radiology units are intended to reduce time consumption in radiology workflow and thus to increase radiologist productivity. Along with the RIS-PACS integration at the University Hospital Innsbruck we analyzed workflow from patient admission to release of final reports before implementation. The follow up study after six months of the implementation is currently in work. In this study we compared chest to skeletal x-ray examinations in 969 patients before the implementation. Drawing the admission-to-release-of-final-report period showed a two-peak diagram with the first peak corresponding to a release of final results on the same day and the second peak to a release on the following day. In the chest x-ray group, 57% were released the same day (mean value 4:02 hours) and 43% the next day (mean value 21:47 hours). Looking at the skeletal x-rays 40% were released the same day (mean value 3:58 hours) and 60% were released the next day (mean value 21:05 hours). Summarizing the results we should say, that the average chest x-ray requires less time than an skeletal x-ray, due to the fact that a greater percentage of reports is released the same day. The most important result is, that the most time consuming workstep is the exchange of data media between radiologist and secretary with at least 5 hours.

  9. Nuclear reactor control apparatus

    DOEpatents

    Sridhar, Bettadapur N.

    1983-11-01

    Nuclear reactor core safety rod release apparatus comprises a control rod having a detent notch in the form of an annular peripheral recess at its upper end, a control rod support tube for raising and lowering the control rod under normal conditions, latches pivotally mounted on the control support tube with free ends thereof normally disposed in the recess in the control rod, and cam means for pivoting the latches out of the recess in the control rod when a scram condition occurs. One embodiment of the invention comprises an additional magnetically-operated latch for releasing the control rod under two different conditions, one involving seismic shock.

  10. How microglia kill neurons.

    PubMed

    Brown, Guy C; Vilalta, Anna

    2015-12-02

    Microglia are resident brain macrophages that become inflammatory activated in most brain pathologies. Microglia normally protect neurons, but may accidentally kill neurons when attempting to limit infections or damage, and this may be more common with degenerative disease as there was no significant selection pressure on the aged brain in the past. A number of mechanisms by which activated microglia kill neurons have been identified, including: (i) stimulation of the phagocyte NADPH oxidase (PHOX) to produce superoxide and derivative oxidants, (ii) expression of inducible nitric oxide synthase (iNOS) producing NO and derivative oxidants, (iii) release of glutamate and glutaminase, (iv) release of TNFα, (v) release of cathepsin B, (vi) phagocytosis of stressed neurons, and (vii) decreased release of nutritive BDNF and IGF-1. PHOX stimulation contributes to microglial activation, but is not directly neurotoxic unless NO is present. NO is normally neuroprotective, but can react with superoxide to produce neurotoxic peroxynitrite, or in the presence of hypoxia inhibit mitochondrial respiration. Glutamate can be released by glia or neurons, but is neurotoxic only if the neurons are depolarised, for example as a result of mitochondrial inhibition. TNFα is normally neuroprotective, but can become toxic if caspase-8 or NF-κB activation are inhibited. If the above mechanisms do not kill neurons, they may still stress the neurons sufficiently to make them susceptible to phagocytosis by activated microglia. We review here whether microglial killing of neurons is an artefact, makes evolutionary sense or contributes in common neuropathologies and by what mechanisms. This article is part of a Special Issue entitled SI: Neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Notice of Changes to the Weekly Natural Gas Storage Report

    EIA Publications

    2015-01-01

    On November 19, 2015, EIA will release the Weekly Natural Gas Storage Report (WNGSR) with new data breakouts for five regions of the Lower 48 states, converting from the current three-region structure. On Monday, November 16, 2015, EIA will re-release the data that will be published on Friday, November 13 (for the week ending Friday, November 6) in the new five-region format. The release will be conducted through the same timed countdown procedures used for normal releases on the same WNGSR web page: http://ir.eia.gov/ngs/ngs.html.

  12. Influence of enteric-coated lactose on the release profile of 4-aminopyridine from HPMC matrix tablets.

    PubMed

    Martínez-González, Ilona; Villafuerte-Robles, Leopoldo

    2004-01-01

    A weakly basic experimental drug, 4-aminopyridine, was taken as a model to study the influence of enteric-coated lactose (EL) on the release profile from hydroxypropyl methylcellulose matrices. Powder mixtures were wet-granulated with water. The dried granulation was compressed with a hydraulic press at 85 MPa. Dissolution studies were made using HCl 0.1 N and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf) = k*t(N). A trend toward increasing exponent (n) and decreasing release constant (k) values is observed with increasing EL concentrations up to 9%; this is attributed to an increasing obstruction of the diffusion path by isolated EL particles that are insoluble in HCl and are surrounded by a water-filled space. After a critical EL concentration, the water-filled spaces surrounding EL particles percolate, producing the opposite effect, increasing the release constant and decreasing the exponent (n) values as the EL proportion increases from 10% to 50%. EL particles (2% to 9%) decrease the drug and water transport in matrices dissolving in HCl. Thereafter, at pH 7.4, the pores formed by dissolution of EL particles produce the opposite. Both processes contribute to flattening the release profile. Release profiles with decreasing release constant values show a logarithmic trend toward increasing values of the exponent (n), changing from diffusion toward relaxation-erosion-controlled processes.

  13. Neuropeptides linking the control of appetite with reproductive function in domestic animals

    USDA-ARS?s Scientific Manuscript database

    The occurrence of puberty and maintenance of normal reproductive cycles are regulated by secretion of gonadotropin hormones from the pituitary gland, which is dependent upon the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. It is well established that secretion of...

  14. Biophysical and Biochemical Mechanisms in Synaptic Transmitter Release.

    DTIC Science & Technology

    1992-01-31

    vesicle is normally released per active zone Sci USA 83. 3032 (1986) pared (15, 19, 20). In fact, in squid, the quantum 8 0 Shimomura 8 Musicki. V Kisni...8217, AND R. LLINAS• *Instituto de Biologia Celular Facultad de Medicina. Universidad de Buenos Aires. Paraguay 2155. Buenos Aires 1121. Argentina: and

  15. 21 CFR 1.360 - What are the record retention requirements?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... release the food all required records for any food having a significant risk of spoilage, loss of value... required records for any food for which a significant risk of spoilage, loss of value, or loss of... release the food all required records for any food for which a significant risk of spoilage, loss of value...

  16. Identification of the release history of a groundwater contaminant in non-uniform flow field through the minimum relative entropy method

    NASA Astrophysics Data System (ADS)

    Cupola, F.; Tanda, M. G.; Zanini, A.

    2014-12-01

    The interest in approaches that allow the estimation of pollutant source release in groundwater has increased exponentially over the last decades. This is due to the large number of groundwater reclamation procedures that have been carried out: the remediation is expensive and the costs can be easily shared among the different actors if the release history is known. Moreover, a reliable release history can be a useful tool for predicting the plume evolution and for minimizing the harmful effects of the contamination. In this framework, Woodbury and Ulrych (1993, 1996) adopted and improved the minimum relative entropy (MRE) method to solve linear inverse problems for the recovery of the pollutant release history in an aquifer. In this work, the MRE method has been improved to detect the source release history in 2-D aquifer characterized by a non-uniform flow-field. The approach has been tested on two cases: a 2-D homogeneous conductivity field and a strong heterogeneous one (the hydraulic conductivity presents three orders of magnitude in terms of variability). In the latter case the transfer function could not be described with an analytical formulation, thus, the transfer functions were estimated by means of the method developed by Butera et al. (2006). In order to demonstrate its scope, this method was applied with two different datasets: observations collected at the same time at 20 different monitoring points, and observations collected at 2 monitoring points at different times (15-25 monitoring points). The data observed were considered affected by a random error. These study cases have been carried out considering a Boxcar and a Gaussian function as expected value of the prior distribution of the release history. The agreement between the true and the estimated release history has been evaluated through the calculation of the normalized Root Mean Square (nRMSE) error: this has shown the ability of the method of recovering the release history even in the most severe cases. Finally, the forward simulation has been carried out by using the estimated release history in order to compare the true data with the estimated one: the best agreement has been obtained in the homogeneous case, even if also in the heterogenous one the nRMSE is acceptable.

  17. Calcium release and its voltage dependence in frog cut muscle fibers equilibrated with 20 mM EGTA

    PubMed Central

    1995-01-01

    Sarcoplasmic reticulum (SR) Ca release was studied at 13-16 degrees C in cut fibers (sarcomere length, 3.4-3.9 microns) mounted in a double Vaseline-gap chamber. The amplitude and duration of the action- potential stimulated free [Ca] transient were reduced by equilibration with end-pool solutions that contained 20 mM EGTA with 1.76 mM Ca and 0.63 mM phenol red, a maneuver that appeared to markedly reduce the amount of Ca complexed by troponin. A theoretical analysis shows that, under these conditions, the increase in myoplasmic free [Ca] is expected to be restricted to within a few hundred nanometers of the SR Ca release sites and to have a time course that essentially matches that of release. Furthermore, almost all of the Ca that is released from the SR is expected to be rapidly bound by EGTA and exchanged for protons with a 1:2 stoichiometry. Consequently, the time course of SR Ca release can be estimated by scaling the delta pH signal measured with phenol red by -beta/2. The value of beta, the buffering power of myoplasm, was determined in fibers equilibrated with a combination of EGTA, phenol red, and fura-2; its mean value was 22 mM/pH unit. The Ca content of the SR (expressed as myoplasmic concentration) was estimated from the total amount of Ca released by either a train of action potentials or a depleting voltage step; its mean value was 2,685 microM in the action-potential experiments and 2,544 microM in the voltage- clamp experiments. An action potential released, on average, 0.14 of the SR Ca content with a peak rate of release of approximately 5%/ms. A second action potential, elicited 20 ms later, released only 0.6 times as much Ca (expressed as a fraction of the SR content), probably because Ca inactivation of Ca release was produced by the first action potential. During a depolarizing voltage step to 60 mV, the rate of Ca release rapidly increased to a peak value of approximately 3%/ms and then decreased to a quasi-steady level that was only 0.6 times as large; this decrease was also probably due to Ca inactivation of Ca release. SR Ca release was studied with small step depolarizations that open no more than one SR Ca channel in 7,000 and increase the value of spatially averaged myoplasmic free [Ca] by only 0.2 nM. PMID:8537818

  18. Water Potential in Excised Leaf Tissue

    PubMed Central

    Nelsen, Charles E.; Safir, Gene R.; Hanson, Andrew D.

    1978-01-01

    Leaf water potential (Ψleaf) determinations were made on excised leaf samples using a commercial dew point hygrometer (Wescor Inc., Logan, Utah) and a thermocouple psychrometer operated in the isopiestic mode. With soybean leaves (Glycine max L.), there was good agreement between instruments; equilibration times were 2 to 3 hours. With cereals (Triticum aestivum L. and Hordeum vulgare L.), agreement between instruments was poor for moderately wilted leaves when 7-mm-diameter punches were used in the hygrometer and 20-mm slices were used in the psychrometer, because the Ψleaf values from the dew point hygrometer were too high. Agreement was improved by replacing the 7-mm punch samples in the hygrometer by 13-mm slices, which had a lower cut edge to volume ratio. Equilibration times for cereals were normally 6 to 8 hours. Spuriously high Ψleaf values obtained with 7-mm leaf punches may be associated with the ion release and reabsorption that occur upon tissue excision; such errors evidently depend both on the species and on tissue water status. PMID:16660227

  19. Combined effect of matrix cracking and stress-free edge on delamination

    NASA Technical Reports Server (NTRS)

    Salpekar, S. A.; Obrien, T. K.

    1990-01-01

    The effect of the stress-free edge on the growth of local delaminations initiating from a matrix crack in (0 sub 2/90 sub 4) sub s and (+ or - 45.90 sub 4) sub s glass epoxy laminates is investigated using 3-D finite element analysis. The presence of high interlaminar normal stresses at the intersection (corner) of the matrix crack with the stress-free edge, suggests that a mode I delamination may initiate at the corners. The strain energy release rates (G) were calculated by modeling a uniform through-width delamination and two inclined delaminations at 10.6 deg and 45 deg to the matrix crack. All components of G have high values near the free edges. The mode I component of G is high at small delamination length and becomes zero for a delamination length of one-ply thickness. The total G values near the free edge agreed well with previously derived closed form solution. The quasi-3D solutions agreed well with the 3-D interior solutions.

  20. Combined effect of matrix cracking and stress-free edge on delamination

    NASA Technical Reports Server (NTRS)

    Salpekar, Satish A.; O'Brien, T. K.

    1991-01-01

    The effect of the stress-free edge on the growth of local delaminations initiating from a matrix crack in (O sub 2/90 sub 4) sub s and (+/- 45.90 sub 4) sub s glass epoxy laminates is investigated using 3D finite element analysis. The presence of high interlaminar normal stresses at the intersection (corner) of the matrix crack with the stress-free edge, suggests that a mode I delamination may initiate at the corners. The strain energy release rates (G) were calculated by modeling a uniform through-width delamination and two inclined delaminations at 10.6 deg and 45 deg to the matrix crack. All components of G have high values near the free edges. The mode I component of G is high at small delamination length and becomes zero for a delamination length of one-ply thickness. The total G values near the free edge agreed well with previously derived closed form solution. The quasi-3D solutions agreed well with the 3D interior solutions.

  1. Toxicity of marine pollutants on the ascidian oocyte physiology: an electrophysiological approach.

    PubMed

    Gallo, Alessandra

    2018-02-01

    In marine animals with external fertilization, gametes are released into seawater where fertilization and embryo development occur. Consequently, pollutants introduced into the marine environment by human activities may affect gametes and embryos. These xenobiotics can alter cell physiology with consequent reduction of fertilization success. Here the adverse effects on the reproductive processes of the marine invertebrate Ciona intestinalis (ascidian) of different xenobiotics: lead, zinc, an organic tin compound and a phenylurea herbicide were evaluated. By using the electrophysiological technique of whole-cell voltage clamping, the effects of these compounds on the mature oocyte plasma membrane electrical properties and the electrical events of fertilization were tested by calculating the concentration that induced 50% normal larval formation (EC50). The results demonstrated that sodium currents in mature oocytes were reduced in a concentration-dependent manner by all tested xenobiotics, with the lowest EC50 value for lead. In contrast, fertilization current frequencies were differently affected by zinc and organic tin compound. Toxicity tests on gametes demonstrated that sperm fertilizing capability and fertilization oocyte competence were not altered by xenobiotics, whereas fertilization was inhibited in zinc solution and underwent a reduction in organic tin compound solution (EC50 value of 1.7 µM). Furthermore, fertilized oocytes resulted in a low percentage of normal larvae with an EC50 value of 0.90 µM. This study shows that reproductive processes of ascidians are highly sensitive to xenobiotics suggesting that they may be considered a reliable biomarker and that ascidians are suitable model organisms to assess marine environmental quality.

  2. Environmental quality of the operating theaters in Campania Region: long lasting monitoring results.

    PubMed

    Triassi, M; Novi, C; Nardone, A; Russo, I; Montuori, P

    2015-01-01

    The health risk level in the operating theaters is directly correlated to the safety level offered by the healthcare facilities. This is the reason why the national Authorities released several regulations in order to monitor better environmental conditions of the operating theaters, to prevent occupational injuries and disease and to optimize working conditions. For the monitoring of environmental quality of the operating theaters following parameters are considered: quantity of supplied gases, anesthetics concentration, operating theatres volume measurement, air change rate, air conditioning system and air filtration. The objective is to minimize the risks in the operating theaters and to provide the optimal environmental working conditions. This paper reports the environmental conditions of operating rooms performed for several years in the public hospitals of the Campania Region. Investigation of environmental conditions of 162 operating theaters in Campania Region from January 2012 till July 2014 was conducted. Monitoring and analysis of physical and chemical parameters was done. The analysis of the results has been made considering specific standards suggested by national and international regulations. The study showed that 75% of the operating theaters presented normal values for microclimatic monitoring, while the 25% of the operating theaters had at least one parameter outside the limits. The monitoring of the anesthetics gases showed that in 9% of measurements of nitrous oxides and 4% of measurements of halogenated was not within the normal values.

  3. Increased Urinary Adenosine Triphosphate in Patients With Bladder Outlet Obstruction Due to Benign Prostate Hyperplasia.

    PubMed

    Silva-Ramos, Miguel; Silva, Isabel; Oliveira, José Carlos; Correia-de-Sá, Paulo

    2016-11-01

    Diagnosis of bladder outflow obstruction (BOO) in patients with lower urinary tract (LUT) symptoms is challenging without using invasive urodynamic tests. Recently, we showed in vitro that urothelial strips from patients with benign prostatic hyperplasia (BPH) release more ATP than controls. Here, we tested whether urinary ATP can be used as a wall tension transducer non-invasive biomarker to detect BOO in patients with BPH. 79 male patients with BOO and 22 asymptomatic controls were recruited prospectively. Patients were asked to complete the International Prostate Symptom Score (IPSS) questionnaire and to void at normal desire into a urinary flowmeter; the postvoid residual volume was determined by suprapubic ultrasonography. Urine samples from all individuals were examined for ATP, creatinine, and lactate dehydrogenase. BOO patients had significantly higher (P < 0.001) urinary ATP normalized by the voided volume (456 ± 36 nmol) than age-matched controls (209 ± 35 nmol). Urinary ATP amounts increased with the voided volume, but the slope of this rise was higher in BOO patients than in controls. A negative correlation was detected between urinary ATP and flow rate parameters, namely maximal flow rate (r = -0.310, P = 0.005), Siroky flow-volume normalization (r = -0.324, P = 0.004), and volume-normalized flow rate index (r = -0.320, P = 0.012). We found no correlation with LUT symptoms IPSS score. Areas under the receiver operator characteristics (ROC) curves were 0.91 (95%CI 0.86-0.96, P < 0.001) for ATP alone and 0.88 (95%CI 0.81-0.94, P < 0,001) when adjusted to urinary creatinine. Patients with BOO release higher amounts of ATP into the urine than the control group. The high area under the ROC curve suggests that urinary ATP can be a high-sensitive non-invasive biomarker of BOO, which may have a discriminative value of detrusor competence when comparing BPH patients with low urinary flow rates. Prostate 76:1353-1363, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Capsaicin-evoked iCGRP release from human dental pulp: a model system for the study of peripheral neuropeptide secretion in normal healthy tissue

    PubMed Central

    Fehrenbacher, Jill C.; Sun, Xiaoling X.; Locke, Erin E.; Henry, Michael A.; Hargreaves, Kenneth M.

    2009-01-01

    The mechanisms underlying trigeminal pain conditions are incompletely understood. In vitro animal studies have elucidated various targets for pharmacological intervention; however, a lack of clinical models that allow evaluation of viable innervated human tissue has impeded successful translation of many preclinical findings into clinical therapeutics. Therefore, we developed and characterized an in vitro method that evaluates the responsiveness of isolated human nociceptors by measuring basal and stimulated release of neuropeptides from collected dental pulp biopsies. Informed consent was obtained from patients presenting for extraction of normal wisdom teeth. Patients were anesthetized using nerve block injection, teeth were extracted and bisected, and pulp was removed and superfused in vitro. Basal and capsaicin-evoked peripheral release of immunoreactive calcitonin gene-related peptide (iCGRP) was analyzed by enzyme immunoassay. The presence of nociceptive markers within neurons of the dental pulp was characterized using confocal microscopy. Capsaicin increased the release of iCGRP from dental pulp biopsies in a concentration-dependent manner. Stimulated release was dependent on extracellular calcium, reversed by a TRPV1 receptor antagonist, and desensitized acutely (tachyphylaxis) and pharmacologically by pretreatment with capsaicin. Superfusion with phorbol 12-myristate 13-acetate (PMA) increased basal and stimulated release, whereas PGE2 augmented only basal release. Compared with vehicle treatment, pretreatment with PGE2 induced competence for DAMGO to inhibit capsaicin-stimulated iCGRP release, similar to observations in animal models where inflammatory mediators induce competence for opioid inhibition. These results indicate the release of iCGRP from human dental pulp provides a novel tool to determine the effects of pharmacological compounds on human nociceptor sensitivity. PMID:19428185

  5. Atmospheric modeling of Mars CH4 subsurface clathrates releases mimicking SAM and 2003 Earth-based detections

    NASA Astrophysics Data System (ADS)

    Pla-Garcia, Jorge

    2017-10-01

    The aim of this work is to establish the amount of mixing during all martian seasons to test whether CH4 releases inside or outside of Gale crater are consistent with MSL-SAM observations. Several modeling scenarios were configured, including instantaneous and steady releases, both inside and outside the crater. A simulation to mimic the 2003 Earth-based detections (Mumma et al. 2009 or M09) was also performed. In the instantaneous release inside Gale experiments, Ls270 was shown to be the faster mixing season when air within and outside the crater was well mixed: all tracer mass inside the crater is diluted after just 8 hours. The mixing of near surface crater air with the external environment in the rest of the year is potentially rapid but slower than Ls270. In the instantaneous release outside Gale (NW) experiment, in just 12 hours the CH4 that makes it to the MSL landing location is diluted by six orders of magnitude. The timescale of mixing in the model is on the order of 1 sol regardless of season. The duration of the CH4 peak observed by SAM is 100 sols. Therefore there is a steady release inside the crater, or there is a large magnitude steady release outside the crater. In the steady release Gale experiments, CH4 flux rate from ground is 1.8 kg m-2 s-1 (Gloesener et al. 2017) and it is not predictive. In these experiments, ~200 times lower CH4 values detected by SAM are modeled around MSL location. There are CH4 concentration variations of orders of magnitude depending on the hour, so timing of SAM measurements is important. With a larger (but further away) outside crater release area compared to inside, similar CH4 values around MSL are modeled, so distance to source is important. In the steady experiments mimicking M09 detection release area, only 12 times lower CH4 values detected by SAM are modeled around MSL. The highest value in the M09 modeled scenario (0.6 ppbv) is reached in Ls270. This value is the highest of all modeled experiments. With our initial conditions, SAM should not be able to detect CH4, but if we multiply flux by 12, increase the release area or move it closer to MSL (or all of above), it may be possible to get CH4 values that SAM could detect regardless where it comes from.

  6. Turbulence-flame interactions in DNS of a laboratory high Karlovitz premixed turbulent jet flame

    NASA Astrophysics Data System (ADS)

    Wang, Haiou; Hawkes, Evatt R.; Chen, Jacqueline H.

    2016-09-01

    In the present work, direct numerical simulation (DNS) of a laboratory premixed turbulent jet flame was performed to study turbulence-flame interactions. The turbulent flame features moderate Reynolds number and high Karlovitz number (Ka). The orientations of the flame normal vector n, the vorticity vector ω and the principal strain rate eigenvectors ei are examined. The in-plane and out-of-plane angles are introduced to quantify the vector orientations, which also measure the flame geometry and the vortical structures. A general observation is that the distributions of these angles are more isotropic downstream as the flame and the flow become more developed. The out-of-plane angle of the flame normal vector, β, is a key parameter in developing the correction of 2D measurements to estimate the corresponding 3D quantities. The DNS results show that the correction factor is unity at the inlet and approaches its theoretical value of an isotropic distribution downstream. The alignment characteristics of n, ω and ei, which reflect the interactions of turbulence and flame, are also studied. Similar to a passive scalar gradient in non-reacting flows, the flame normal has a tendency to align with the most compressive strain rate, e3, in the flame, indicating that turbulence contributes to the production of scalar gradient. The vorticity dynamics are examined via the vortex stretching term, which was found to be the predominant source of vorticity generation balanced by dissipation, in the enstrophy transport equation. It is found that although the vorticity preferentially aligns with the intermediate strain rate, e2, the contribution of the most extensive strain rate, e1, to vortex stretching is comparable with that of the intermediate strain rate, e2. This is because the eigenvalue of the most extensive strain rate, λ1, is always large and positive. It is confirmed that the vorticity vector is preferentially positioned along the flame tangential plane, contributing to the dominance of cylindrical curvature of the flame front. Finally, the effect of heat release on the turbulence-flame interactions is examined. It is found that heat release has only limited impact on the statistics due to the minor role played by the strain rate induced by heat release rate in the current high Ka flame.

  7. Tibiofemoral contact mechanics following posterior root of medial meniscus tear, repair, meniscectomy, and allograft transplantation.

    PubMed

    Kim, Jin Goo; Lee, Yong Seuk; Bae, Tae Soo; Ha, Jeong Ku; Lee, Dong Hoon; Kim, Young Jae; Ra, Ho Jong

    2013-09-01

    The purposes of this study were to evaluate the effect on tibiofemoral contact mechanics of repair of the posterior root of the medial meniscus and the effect of meniscal allograft transplantation (MAT) with medial collateral ligament (MCL) release at different flexion angles. Ten fresh-frozen human cadaveric knees (five pairs) were used. A digital pressure sensor was inserted by capsulotomy, and experiments were performed serially under the following six conditions, that is, with an intact medial meniscus (normal controls), with a root tear, after root repair, after total meniscectomy, after MAT, and after MAT plus MCL release. During each experiment, knees were positioned at 0°, 30°, 60°, and 90° of flexion, and peak pressure (kPa) and contact area (cm2) were measured. At 0° of flexion, contact pressure did not differ among the six experimental settings. However, at 30° and 60° of flexion, contact pressure differed significantly between root tear and root repair specimens (p = 0.04 and 0.03, respectively), and between total meniscectomy and MAT specimens (p = 0.02 and 0.03, respectively). On the other hand, mean contact pressures were different between normal (476.7 ± 473.1 and 573.3 ± 479.1 kPa) and root repair (575.7 ± 357.8 and 598.6 ± 415.8), and between normal and MAT (635.7 ± 437.4 and 674.3 ± 533.2). At 0°, 30°, 60°, and 90° of flexion, contact areas differed significantly between normal and total meniscectomy specimens (p = 0.02, 0.01, 0.02, and 0.02, respectively), and between MAT and total meniscectomy specimens (p = 0.03, 0.02, 0.02, and 0.03, respectively). Contact areas differed significantly between root tear and root repair specimens at 60° of flexion (p = 0.04), and between normal control and root repair specimens at 60° and 90° of flexion (p = 0.03 and 0.04, respectively). The effects of MAT plus MCL release on contact mechanics were not different from the effects of MAT alone (n.s.). Both meniscal root repair and transplantation of meniscus improved contact mechanics, but it did not appear that repair of the meniscal root or transplantation of meniscus restores the biomechanical function back to normal level. The MAT plus MCL release was similar to those after MAT alone. Therefore, it is better to preserve meniscus and MCL release could be done during the MAT.

  8. [The effects of various factors on the in vitro velocity of drug release from repository tablets. Part 4: Isoniazid (Rimicid) respository tablets (author's transl)].

    PubMed

    Tomassini, L; Michailova, D; Naplatanova, D; Slavtschev, P

    1979-12-01

    The authors investigated the release of isoniazid from repository tablets as related to form, processing technology, strength constant and storage for 5 years. On determining the diffusion coefficient (D), the initial dissolution rate (Vo) and the time required for the diffusion of the releasing medium to the middle of the tablet (t1/2), it was found that the difference in release rate between the flat and the biconvex tablets is small. Furthermore, it was stated that the three-layer tablets have very high D and Vo values and very low t1/2 values, for what reason they are unsuited for repository tablets of the composition under investigation. Moreover, it was found that an increase of the strength constant does not affect the D, t1/2 and Vo values, and that the release of isoniazid is retarded only in flat tablets with the highest strength constant. Storage exerts no effect on the drug release from these tablets. The industrial production of these tablets is under way.

  9. A velocity-dependent shortening depression in the development of the force-velocity relation in frog muscle fibres.

    PubMed Central

    Colomo, F; Lombardi, V; Piazzesi, G

    1986-01-01

    During the onset of activation in isolated frog muscle fibres the development of the force-velocity (T-V) relation was determined by imposing single and double ramp releases. The experiments were performed at 3.5-6 degrees C or 19-22 degrees C and at a starting sarcomere length of about 2.25 micron. A velocity- and time-dependent shortening deactivation was shown to exist during the development of contraction. It was found that, early during the tetanus rise, at submaximal levels of activation, the values of T (the steady force exerted by the muscle fibres at any velocity of shortening V lower than V0) were significantly affected by previous conditioning shortening. Conditioning shortening at lower speeds led to potentiation of T and, at higher speeds, to depression. Both these effects were independent of the amount of shortening and, in addition, were not present at the tetanus plateau. At each given time or isometric tension throughout the tetanus rise the values of T. normalized for those determined at the same velocities at the tetanus plateau, were found to be inversely correlated with the actual velocities of shortening. The slope of this relation (a measure of the velocity-dependent shortening deactivation) decreased exponentially with time, attaining, in six fibres at low temperature, 10% of its initial value within 26-73 ms. The results may be explained in terms of a cross-bridge model of contraction by assuming that the rate of development of activation is controlled by the rate of release of the Ca2+ as well as by the velocity at which the muscle fibres are allowed to shorten and in turn by the actual number of attached cross-bridges. PMID:3497263

  10. Pituitary response to thyrotropin releasing hormone in children with overweight and obesity.

    PubMed

    Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

    2016-08-03

    Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.

  11. Pituitary response to thyrotropin releasing hormone in children with overweight and obesity

    PubMed Central

    Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

    2016-01-01

    Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9–5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r2 = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r2 = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies. PMID:27485208

  12. Astressin B, a corticotropin-releasing hormone receptor antagonist, accelerates the return to normal luteal function after an inflammatory-like stress challenge in the rhesus monkey.

    PubMed

    Xiao, Ennian; Xia-Zhang, Linna; Vulliemoz, Nicolas; Rivier, Jean; Ferin, Michel

    2007-02-01

    Endogenous release of CRH in stress has been associated with a dysfunctional reproductive endocrine axis. In the rhesus monkey, an inflammatory-like stress challenge in the luteal phase decreases luteal secretory function. Here, we tested the effectiveness of astressin B, a nonspecific CRH receptor antagonist, in constraining the deleterious impact of a 10-d lipopolysaccharide (LPS) challenge on the menstrual cycle. Two protocols were carried out in nine animals. In the first, the animals, after showing two normal consecutive control cycles, were injected daily for 10 days with LPS (75-125 mug/d) during the luteal phase of the cycle. The animals were followed through the two postchallenge cycles. The second protocol, carried out in the following year, was identical with protocol 1, except that the animals were treated with astressin B (0.45 mg/kg) 1 h before each daily LPS challenge during the luteal phase. Blood samples were obtained daily to document cyclic hormones levels. The LPS challenge significantly decreased luteal progesterone and LH release during the challenge cycle. Inhibition of luteal progesterone extended to the two successive postchallenge cycles. Astressin B treatment prevented luteal LH but not luteal progesterone decrease during the treatment cycle and restored normal progesterone secretion during the two posttreatment cycles. We conclude that the deleterious impact of a short-term inflammatory stress challenge on luteal function is far longer than the stress period itself. Systemic administration of astressin B accelerates the return to normal luteal function, presumably by restoring normal neuroendocrine regulation of gonadotropin secretion.

  13. Disease-responsive drug delivery: the next generation of smart delivery devices.

    PubMed

    Wanakule, Prinda; Roy, Krishnendu

    2012-01-01

    With the advent of highly potent and cytotoxic drugs, it is increasingly critical that they be targeted and released only in cells of diseased tissues, while sparing physiologically normal neighbors. Simple ligand-based targeting of drug carriers, although promising, cannot always provide the required specificity to achieve this since often normal cells also express significant levels of the targeted receptors. Therefore, stimuli-responsive delivery systems are being explored to allow drug release from nano- and microcarriers and implantable devices, primarily in the presence of physiological or disease-specific pathophysiological signals. Designing smart biomaterials that respond to temperature or pH changes, protein and ligand binding, disease-specific degradation, e.g. enzymatic cleavage, has become an integral part of this approach. These strategies are used in combination with nano- and microparticle systems to improve delivery efficiency through several routes of administration, and with injectable or implantable systems for long term controlled release. This review focuses on recent developments in stimuli-responsive systems, their physicochemical properties, release profiles, efficacy, safety and biocompatibility, as well as future perspectives.

  14. Renal glucose metabolism in normal physiological conditions and in diabetes.

    PubMed

    Alsahli, Mazen; Gerich, John E

    2017-11-01

    The kidney plays an important role in glucose homeostasis via gluconeogenesis, glucose utilization, and glucose reabsorption from the renal glomerular filtrate. After an overnight fast, 20-25% of glucose released into the circulation originates from the kidneys through gluconeogenesis. In this post-absorptive state, the kidneys utilize about 10% of all glucose utilized by the body. After glucose ingestion, renal gluconeogenesis increases and accounts for approximately 60% of endogenous glucose release in the postprandial period. Each day, the kidneys filter approximately 180g of glucose and virtually all of this is reabsorbed into the circulation. Hormones (most importantly insulin and catecholamines), substrates, enzymes, and glucose transporters are some of the various factors influencing the kidney's role. Patients with type 2 diabetes have an increased renal glucose uptake and release in the fasting and the post-prandial states. Additionally, glucosuria in these patients does not occur at plasma glucose levels that would normally produce glucosuria in healthy individuals. The major abnormality of renal glucose metabolism in type 1 diabetes appears to be impaired renal glucose release during hypoglycemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Functional central hypothyroidism in the elderly.

    PubMed

    Sell, Maren A; Schott, Matthias; Tharandt, Lutz; Cissewski, Klaus; Scherbaum, Werner A; Willenberg, Holger S

    2008-06-01

    Previous studies have shown that blood concentrations of free thyroxin and basal thyroid-stimulating hormone (TSH) decrease during adult life. Suggested mechanisms include reduced thyroid activity resulting from decreased serum TSH concentrations, impairment of peripheral 5'-deiodinase, and an increase in reverse 3,5,3'-triiodothyronine due to non-thyroidal illness. However, testing of pituitary reserves leads to contradictory results and has infrequently been evaluated in studies. We investigated whether the response of TSH to thyrotropin-releasing hormone (TRH) is preserved during aging. This was tested in a cohort of 387 subjects aged 13 to 100 years in whom thyroid disease was excluded by normal thyroid ultrasound, normal values for free thyroxin, free triiodothyronin, TSH, and negative thyroid peroxidase antibodies. Serum concentrations of free thyroxin remained almost unchanged, whereas free triiodothyronin and TSH levels were lower in older subjects. In addition, the TSH response to TRH was blunted in older subjects, especially in male individuals. There is evidence that the decreased thyroid hormone levels observed in aging are due to lower TSH concentrations, and that lower TSH concentrations may be linked to an impaired pituitary activity.

  16. Analysis of Interface Properties of Hybrid Pre-stressed Strengthening RC Beams with Crack

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

    Xie Zhihong; Huang Peiyan; Guo Yongchang

    2010-05-21

    A finite element (FE) analysis model of interface layer is established for the pre-stressed CFS-GFS hybrid strengthened beams. An elastic solution for the interfacial stress in the adhesive layer of the retrofitted beams is developed as well. The analytical results were compared with the FE results of interfacial stresses in the beams with different thickness of the adhesive and the fibre sheet. Different heights of Cracks in the interfacial layer of the concrete beam are considered in FE Model. Analysis results show the strengthening pattern is of excellent interface performance and the strength of the fiber sheet can be effectivelymore » utilized. The results also indicate the shear and normal stresses in the interfacial layer of the concrete beam release at the locations of the cracks and reach the maximal value before the concrete cracked. The shear and normal stresses in the adhesive layer increase abruptly, and the cracks in the adhesive layer then appear. The axial stresses of hybrid fiber sheet near the cracks decrease locally at the sites of the concrete cracks.« less

  17. Oral cancer detection based on fluorescence polarization of blood plasma at excitation wavelength 405 nm

    NASA Astrophysics Data System (ADS)

    Pachaiappan, Rekha; Prakasarao, Aruna; Manoharan, Yuvaraj; Dornadula, Koteeswaran; Singaravelu, Ganesan

    2017-02-01

    During metabolism the metabolites such as hormones, proteins and enzymes were released in to the blood stream by the cells. These metabolites reflect any change that occurs due to any disturbances in normal metabolic function of the human system. This was well observed with the altered spectral signatures observed with fluorescence spectroscopic technique. Previously many have reported on the significance of native fluorescence spectroscopic method in the diagnosis of cancer. As fluorescence spectroscopy is sensitive and simple, it has complementary techniques such as excitation-emission matrix, synchronous and polarization. The fluorescence polarization measurement provides details about any association or binding reactions and denaturing effects that occurs due to change in the micro environment of cells and tissues. In this study, we have made an attempt in the diagnosis of oral cancer at 405 nm excitation using fluorescence polarization measurement. The fluorescence anisotropic values calculated from polarized fluorescence spectral data of normal and oral cancer subjects yielded a good accuracy when analyzed with linear discriminant analysis based artificial neural network. The results will be discussed in detail.

  18. Altered K+ fluxes and insulin release in pancreatic islets from omega3 fatty acid-depleted rats.

    PubMed

    Sener, Abdullah; Zhang, Ying; Louchami, Karim; Oguzhan, Berrin; Courtois, Philippe; Portois, Laurence; Chardigny, Jean-Michel; Carpentier, Yvon A; Malaisse, Willy J

    2006-10-01

    A low intake of long-chain polyunsaturated omega3 fatty acid often prevails in Western populations. Its consequences in terms of the control of fuel homeostasis led us to explore functional events in pancreatic islets isolated from either normal or omega3-depleted rats (second generation). In the latter rats, the inflow of K+ by both ouabain-sensitive and ouabain-resistant modalities was decreased, this coinciding with an impaired insulin secretory response to ouabain. The intravenous injection of a medium-chain triglyceride:fish oil emulsion to omega3-depleted rats 2 h before sacrifice restored a normal value for the inflow of K+ by the ouabainsensitive modality, i.e., that linked to the activity of the Na,K-ATPase, but failed to correct the entry of K+ by the ouabain-resistant modality and the defect of the insulin secretory response to ouabain. In conclusion, an impaired activity of the Na,K-ATPase in insulin-producing cells apparently represents a key determinant of altered islet function in omega3-depleted rats.

  19. The relationship between functional sciatic nerve block duration and the rate of release of lidocaine from a controlled-release matrix.

    PubMed

    Gerner, Peter; Wang, Chi-Fei; Lee, Byung-Sang; Suzuki, Suzuko; Degirolami, Umberto; Gandhi, Ankur; Knaack, David; Strichartz, Gary

    2010-07-01

    Nerve blocks of long duration are often desirable in perioperative and postoperative situations. The relationship between the duration of such blocks and the rate at which a local anesthetic is released is important to know for developing a localized drug delivery system that will optimize block duration. Lidocaine concentration was varied in 1 series of formulations (OSB-L) containing a constant amount of release rate modifier. In another series (OST-R), the release rate modifier was varied while the lidocaine content was held constant. Release kinetics were measured in vitro and correlated to the in vivo duration of antinociceptive and motor block effects when the formulation was implanted next to the rat sciatic nerve. In parallel studies, rats receiving different formulations of slow-release lidocaine were fixed by intracardiac perfusion with 4% paraformaldehyde and nerve-muscle tissue taken for histopathological analysis. In this study, we have demonstrated that the most important variable for effecting functional nerve block, i.e., the blockade of impulses in the relevant fibers of the sciatic nerve, is the rate of lidocaine release at that time. For the OSB-L formulations (lidocaine concentrations of 1.875%, 3.75%, 7.5%, and 15% at a constant release rate modifier of 5%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 0.91 +/- 0.28 and 1.75 +/- 0.61 mg/h, respectively. For the OST-R formulations (16% lidocaine with release rate modifier concentrations of 1.875%, 3.75%, 7.5%, and 15%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 2.33 +/- 1.39 and 4.34 +/- 1.09 mg/h, respectively. The OSB-L formulations showed a dose-dependent increase in block duration proportional to an increase in initial lidocaine concentration, whereas the OST-R formulations showed a nonmonotonic relationship between release rate modifier concentration and block duration. The histopathological studies at 24 hours, 3, 5, or 7 days, and 4 weeks after the implantation revealed inflammatory reactions with degrees correlated with lidocaine content, but limited to the connective tissue and muscle immediately surrounding the implanted material. Despite these observed inflammatory reactions, nociceptive and motor block function returned to normal, preimplantation values in all animals. Increasing initial lidocaine content proportionately increased the duration of functional sciatic nerve block. However, decreasing the release rate per se does not give a proportional increase in block duration. Instead, there seems to be an optimal, intermediate release rate for achieving the maximum duration of block.

  20. Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.

    PubMed Central

    Grainick, H R; Williams, S B; McKeown, L P; Rick, M E; Maisonneuve, P; Jenneau, C; Sultan, Y

    1985-01-01

    We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin-induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia. The platelet-rich plasma of these patients aggregates spontaneously without the addition of any agonists. When isolated normal platelets are resuspended in patient plasma spontaneous aggregation occurs; however, the patients' plasmas did not induce platelet aggregation of normal washed formalinized platelets. When the patients' platelets are suspended in normal plasma, spontaneous aggregation is not observed. The spontaneous platelet aggregation (SPA) is associated with dense granule secretion as measured by ATP release and alpha granule release as measured by beta-thromboglobulin and platelet factor 4 release. The SPA is totally inhibited by 5 mM EDTA, prostaglandin I2, and dibutryl cyclic AMP, while it is only partially inhibited by 1 mM EDTA, acetylsalicylic acid, or apyrase. A monoclonal antibody directed against glycoprotein Ib (GPIb) and/or a monoclonal antibody against the glycoprotein IIb/IIIa (GPIIb/IIIa) complex totally inhibits the SPA. The vWf was isolated from the plasma of one of these patients. The purified vWf induced platelet aggregation of normal platelets resuspended in either normal or severe vWd plasma, but the vWf did not induce platelet aggregation of normal platelets resuspended in afibrinognemic plasma. Sialic acid and galactose quantification of the patient's vWf revealed approximately a 50% reduction compared with normal vWf. These studies indicate that a form of vWd exists, which is characterized by SPA that is induced by the abnormal plasma vWf. The SPA is dependent on the presence of plasma fibrinogen, and the availability of the GPIb and the GPIIb/IIIa complex. In this variant form of vWd the abnormal vWf causes enhanced RIPA, SPA, and thrombocytopenia. Images PMID:2932469

  1. Size-amplified acoustofluidic separation of circulating tumor cells with removable microbeads

    NASA Astrophysics Data System (ADS)

    Liu, Huiqin; Ao, Zheng; Cai, Bo; Shu, Xi; Chen, Keke; Rao, Lang; Luo, Changliang; Wang, Fu-Bin; Liu, Wei; Bondesson, Maria; Guo, Shishang; Guo, Feng

    2018-06-01

    Isolation and analysis of rare circulating tumor cells (CTCs) is of great interest in cancer diagnosis, prognosis, and treatment efficacy evaluation. Acoustofluidic cell separation becomes an attractive method due to its contactless, noninvasive, simple, and versatile features. However, the indistinctive physical difference between CTCs and normal blood cells limits the purity of CTCs using current acoustic methods. Herein, we demonstrate a size-amplified acoustic separation and release of CTCs with removable microbeads. CTCs selectively bound to size-amplifiers (40 μm-diameter anti-EpCAM/gelatin-coated SiO2 microbeads) have significant physical differences (size and mechanics) compared to normal blood cells, resulting in an amplification of acoustic radiation force approximately a hundredfold over that of bare CTCs or normal blood cells. Therefore, CTCs can be efficiently sorted out with size-amplifiers in a traveling surface acoustic wave microfluidic device and released from size-amplifiers by enzymatic degradation for further purification or downstream analysis. We demonstrate a cell separation from blood samples with a total efficiency (E total) of ∼ 77%, purity (P) of ∼ 96%, and viability (V) of ∼83% after releasing cells from size-amplifiers. Our method substantially improves the emerging application of rare cell purification for translational medicine.

  2. Cytotoxic effects of Mangifera indica L. kernel extract on human breast cancer (MCF-7 and MDA-MB-231 cell lines) and bioactive constituents in the crude extract.

    PubMed

    Abdullah, Al-Shwyeh Hussah; Mohammed, Abdulkarim Sabo; Abdullah, Rasedee; Mirghani, Mohamed Elwathig Saeed; Al-Qubaisi, Mothanna

    2014-06-25

    Waterlily Mango (Mangifera indica L.) is thought to be antioxidant-rich, conferred by its functional phytochemicals. The potential anticancer effects of the ethanolic kernel extract on breast cancer cells (MDA-MB-231 and MCF-7) using MTT, anti-proliferation, neutral red (NR) uptake and lactate dehydrogenase (LDH) release assays were evaluated. Cytological studies on the breast cancer cells were also conducted, and phytochemical analyses of the extract were carried out to determine the likely bioactive compounds responsible for such effects. Results showed the extract induced cytotoxicity in MDA-MB-231 cells and MCF-7 cells with IC50 values of 30 and 15 μg/mL, respectively. The extract showed significant toxicity towards both cell lines, with low toxicity to normal breast cells (MCF-10A). The cytotoxic effects on the cells were further confirmed by the NR uptake, antiproliferative and LDH release assays. Bioactive analyses revealed that many bioactives were present in the extract although butylated hydroxytoluene, a potent antioxidant, was the most abundant with 44.65%. M. indica extract appears to be more cytoxic to both estrogen positive and negative breast cancer cell lines than to normal breast cells. Synergistic effects of its antioxidant bioactives could have contributed to the cytotoxic effects of the extract. The extract of M. indica, therefore, has potential anticancer activity against breast cancer cells. This potential is worth studying further, and could have implications on future studies and eventually management of human breast cancers.

  3. Cytotoxic effects of Mangifera indica L. kernel extract on human breast cancer (MCF-7 and MDA-MB-231 cell lines) and bioactive constituents in the crude extract

    PubMed Central

    2014-01-01

    Background Waterlily Mango (Mangifera indica L.) is thought to be antioxidant-rich, conferred by its functional phytochemicals. Methods The potential anticancer effects of the ethanolic kernel extract on breast cancer cells (MDA-MB-231 and MCF-7) using MTT, anti-proliferation, neutral red (NR) uptake and lactate dehydrogenase (LDH) release assays were evaluated. Cytological studies on the breast cancer cells were also conducted, and phytochemical analyses of the extract were carried out to determine the likely bioactive compounds responsible for such effects. Results Results showed the extract induced cytotoxicity in MDA-MB-231 cells and MCF-7 cells with IC50 values of 30 and 15 μg/mL, respectively. The extract showed significant toxicity towards both cell lines, with low toxicity to normal breast cells (MCF-10A). The cytotoxic effects on the cells were further confirmed by the NR uptake, antiproliferative and LDH release assays. Bioactive analyses revealed that many bioactives were present in the extract although butylated hydroxytoluene, a potent antioxidant, was the most abundant with 44.65%. Conclusions M. indica extract appears to be more cytoxic to both estrogen positive and negative breast cancer cell lines than to normal breast cells. Synergistic effects of its antioxidant bioactives could have contributed to the cytotoxic effects of the extract. The extract of M. indica, therefore, has potential anticancer activity against breast cancer cells. This potential is worth studying further, and could have implications on future studies and eventually management of human breast cancers. PMID:24962691

  4. Spatial Release From Masking in 2-Year-Olds With Normal Hearing and With Bilateral Cochlear Implants

    PubMed Central

    Hess, Christi L.; Misurelli, Sara M.; Litovsky, Ruth Y.

    2018-01-01

    This study evaluated spatial release from masking (SRM) in 2- to 3-year-old children who are deaf and were implanted with bilateral cochlear implants (BiCIs), and in age-matched normal-hearing (NH) toddlers. Here, we examined whether early activation of bilateral hearing has the potential to promote SRM that is similar to age-matched NH children. Listeners were 13 NH toddlers and 13 toddlers with BiCIs, ages 27 to 36 months. Speech reception thresholds (SRTs) were measured for target speech in front (0°) and for competitors that were either Colocated in front (0°) or Separated toward the right (+90°). SRM was computed as the difference between SRTs in the front versus in the asymmetrical condition. Results show that SRTs were higher in the BiCI than NH group in all conditions. Both groups had higher SRTs in the Colocated and Separated conditions compared with Quiet, indicating masking. SRM was significant only in the NH group. In the BiCI group, the group effect of SRM was not significant, likely limited by the small sample size; however, all but two children had SRM values within the NH range. This work shows that to some extent, the ability to use spatial cues for source segregation develops by age 2 to 3 in NH children and is attainable in most of the children in the BiCI group. There is potential for the paradigm used here to be used in clinical settings to evaluate outcomes of bilateral hearing in very young children. PMID:29761735

  5. Atmospheric modeling of Mars CH4 subsurface clathrates releases mimicking SAM and 2003 Earth-based detections

    NASA Astrophysics Data System (ADS)

    Pla-García, J.; Rafkin, S. C.

    2017-12-01

    The aim of this work is to establish the amount of mixing during all martian seasons to test whether CH4 releases inside or outside of Gale crater are consistent with MSL-SAM observations. Several modeling scenarios were configured, including instantaneous and steady releases, both inside and outside the crater. A simulation to mimic the 2003 Earth-based detections (Mumma et al. 2009 or M09) was also performed. In the instantaneous release inside Gale experiments, Ls270 was shown to be the faster mixing season when air within and outside the crater was well mixed: all tracer mass inside the crater is diluted after just 8 hours. The mixing of near surface crater air with the external environment in the rest of the year is potentially rapid but slower than Ls270.In the instantaneous release outside Gale (NW) experiment, in just 12 hours the CH4 that makes it to the MSL landing location is diluted by six orders of magnitude. The timescale of mixing in MRAMS experiments is on the order of 1 sol regardless of season. The duration of the CH4 peak observed by SAM is 100 sols. Therefore there is a steady release inside the crater, or there is a very large magnitude steady release outside the crater. In the steady release Gale experiments, CH4 flux rate from ground is 1.8 kg m-2 s-1 (derived from Gloesener et al. 2017 clathrates fluxes) and it is not predictive. In these experiments, 200 times lower CH4 values detected by SAM are modeled around MSL location. There are CH4 concentration variations of orders of magnitude depending on the hour, so timing of SAM measurements is important. With a larger (but further away) outside crater release area compared to inside, similar CH4 values around MSL are modeled, so distance to source is important. In the steady experiments mimicking M09 detection release area, only 12 times lower CH4 values detected by SAM are modeled around MSL. The highest value in the M09 modeled scenario (0.6 ppbv) is reached in Ls270. This value is the highest of all modeled experiments. With our initial conditions (flux rates, release area size and distance to MSL), SAM should not be able (or very difficult) to detect CH4, but if we multiply flux by 12, increase the release area or move it closer to MSL (or all of above), it may be possible to get CH4 values that SAM could detect regardless where it comes from: inside, outside (close to) or far away from Gale.

  6. Proinflammatory cytokine activities, matrix metalloproteinase-3 activity, and sulfated glycosaminoglycan content in synovial fluid of dogs with naturally acquired cranial cruciate ligament rupture.

    PubMed

    Fujita, Yukihiro; Hara, Yasushi; Nezu, Yoshinori; Schulz, Kurt S; Tagawa, Masahiro

    2006-06-01

    To measure and compare activities of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinase-3 (MMP-3); as well as sulfated glycosaminoglycan (S-GAG) content in synovial fluid from dogs with cranial cruciate ligament rupture (CCLR) and dogs with clinically normal stifles. To determine whether correlations exist between demographic and disease-related variables and these synovial markers. Prospective clinical study. Dogs with CCLR (n=23) and Beagles with normal stifle joints (n=21). Synovial fluid activities of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) were determined by bioassay. MMP-3 activity was measured using fluorogenic substrate. S-GAG contents were determined by dimethylmethylene blue dye-binding assay. Mann-Whitney U-test was used to compare results from CCLR joints with normal controls. Spearman's rank correlation test was used to evaluate associations between demographic and disease-related markers and synovial markers. Mean values for synovial markers were significantly higher in CCLR joints compared with controls. IL-1beta and MMP-3 were positively correlated with lameness duration. Activities of proinflammatory cytokines, MMP-3 activity and S-GAG contents were significantly elevated in synovial fluid from canine stifle joints with naturally acquired CCLR. These results indicate that there is joint inflammation and increased release of GAGs into synovial fluid, suggesting that these inflammatory changes are associated with depletion of proteoglycan from articular cartilage. Medical and surgical treatments designed to decrease joint inflammation and breakdown of proteoglycans may be of value in the management of CCLR in the dog.

  7. Regulation of insulin secretion from islets of Langerhans rendered permeable by electric discharge

    PubMed Central

    Yaseen, M. Adel; Pedley, Kevin C.; Howell, Simon L.

    1982-01-01

    1. High-voltage electric discharge has been used to increase the permeability of B-cells of isolated islets of Langerhans to facilitate studies of the effects of normally impermeable substances on insulin secretion. 2. The application of an intense electric field increased the [14C]sucrose space of the islets from 37.8±3.1% to 86.2±5.2% of their total volume as assessed by 3H2O content. The cells remained permeable for at least 40min. 3. Ultrastructural studies showed no deleterious changes in the structure of the B-cells after discharge. 4. Insulin secretion from normal islets was unaffected by increasing the medium [Ca2+] from 10nm to 10μm. In the islets that had been rendered permeable by discharge, insulin secretion was significantly increased under these conditions, without any alteration in the release of lactate dehydrogenase, a cytoplasmic marker enzyme. 5. Studies of the dynamics of insulin release during perifusion showed that the response to increased (10μm) Ca2+ concentration was rapid and sustained over a period of at least 13min. 6. Secretion responses to Ca2+ in perifusion established that maximum release in permeabilized islets occurs at approx. 1μm-Ca2+ and half-maximum release occurs at approx. 0.6μm-Ca2+. 7. The study of the effect of agents that interfere with the microtubular microfilamentous system in B-cells using a perifusion system revealed that cytochalasin B caused a considerable increase, whereas vinblastine sulphate caused a significant inhibition, in insulin release in response to 1μm-Ca2+. 8. This technique should facilitate the study of the role of normally impermeable ions and metabolic intermediates in the regulation of insulin secretion. ImagesPLATE 1 PMID:6751326

  8. Mechanical properties of the human hand digits: Age-related differences

    PubMed Central

    Park, Jaebum; Pazin, Nemanja; Friedman, Jason; Zatsiorsky, Vladimir M.; Latash, Mark L.

    2014-01-01

    Background Mechanical properties of human digits may have significant implications for the hand function. We quantified several mechanical characteristics of individual digits in young and older adults. Methods Digit tip friction was measured at several normal force values using a method of induced relative motion between the digit tip and the object surface. A modified quick-release paradigm was used to estimate digit apparent stiffness, damping, and inertial parameters. The subjects grasped a vertical handle instrumented with force/moment sensors using a prismatic grasp with four digits; the handle was fixed to the table. Unexpectedly, one of the sensors yielded leading to a quick displacement of the corresponding digit. A second-order, linear model was used to fit the force/displacement data. Findings Friction of the digit pads was significantly lower in older adults. The apparent stiffness coefficient values were higher while the damping coefficients were lower in older adults leading to lower damping ratio. The damping ratio was above unity for most data in young adults and below unity for older adults. Quick release of a digit led to force changes in other digits of the hand, likely due to inertial hand properties. These phenomena of “mechanical enslaving” were smaller in older adults although no significant difference was found in the inertial parameter in the two groups. Interpretations The decreased friction and damping ratio present challenges for the control of everyday prehensile tasks. They may lead to excessive digit forces and low stability of the grasped object. PMID:24355703

  9. Factors affecting speech understanding in gated interference: Cochlear implant users and normal-hearing listeners

    NASA Astrophysics Data System (ADS)

    Nelson, Peggy B.; Jin, Su-Hyun

    2004-05-01

    Previous work [Nelson, Jin, Carney, and Nelson (2003), J. Acoust. Soc. Am 113, 961-968] suggested that cochlear implant users do not benefit from masking release when listening in modulated noise. The previous findings indicated that implant users experience little to no release from masking when identifying sentences in speech-shaped noise, regardless of the modulation frequency applied to the noise. The lack of masking release occurred for all implant subjects who were using three different devices and speech processing strategies. In the present study, possible causes of this reduced masking release in implant listeners were investigated. Normal-hearing listeners, implant users, and normal-hearing listeners presented with a four-band simulation of a cochlear implant were tested for their understanding of sentences in gated noise (1-32 Hz gate frequencies) when the duty cycle of the noise was varied from 25% to 75%. No systematic effect of noise duty cycle on implant and simulation listeners' performance was noted, indicating that the masking caused by gated noise is not only energetic masking. Masking release significantly increased when the number of spectral channels was increased from 4 to 12 for simulation listeners, suggesting that spectral resolution is important for masking release. Listeners were also tested for their understanding of gated sentences (sentences in quiet interrupted by periods of silence ranging from 1 to 32 Hz as a measure of auditory fusion, or the ability to integrate speech across temporal gaps. Implant and simulation listeners had significant difficulty understanding gated sentences at every gate frequency. When the number of spectral channels was increased for simulation listeners, their ability to understand gated sentences improved significantly. Findings suggest that implant listeners' difficulty understanding speech in modulated conditions is related to at least two (possibly related) factors: degraded spectral information and limitations in auditory fusion across temporal gaps.

  10. Spent fuel radionuclide source-term model for assessing spent fuel performance in geological disposal. Part I: Assessment of the instant release fraction

    NASA Astrophysics Data System (ADS)

    Johnson, Lawrence; Ferry, Cécile; Poinssot, Christophe; Lovera, Patrick

    2005-11-01

    A source-term model for the short-term release of radionuclides from spent nuclear fuel (SNF) has been developed. It provides quantitative estimates of the fraction of various radionuclides that are expected to be released rapidly (the instant release fraction, or IRF) when water contacts the UO 2 or MOX fuel after container breaching in a geological repository. The estimates are based on correlation of leaching data for radionuclides with fuel burnup and fission gas release. Extrapolation of the data to higher fuel burnup values is based on examination of data on fuel restructuring, such as rim development, and on fission gas release data, which permits bounding IRF values to be estimated assuming that radionuclide releases will be less than fission gas release. The consideration of long-term solid-state changes influencing the IRF prior to canister breaching is addressed by evaluating alpha self-irradiation enhanced diffusion, which may gradually increase the accumulation of fission products at grain boundaries.

  11. Can hi-jacking hypoxia inhibit extracellular vesicles in cancer?

    PubMed

    Lowry, Michelle C; O'Driscoll, Lorraine

    2018-06-01

    Increasing evidence indicates that extracellular vesicles (EVs) are key players in undesirable cell-cell communication in cancer. However, the release of EVs is not unique to cancer cells; normal cells release EVs to perform physiological roles. Thus, selective inhibition of EV release from cancer cells is desirable. Hypoxia contributes to tumour development and aggressiveness. EV quantities and thus undesirable communications are substantially increased in hypoxia. Targeting hypoxia could selectively inhibit EV release from tumour cells without disturbing physiologically relevant EVs. The unfavourable association between hypoxia and EV release is evident in multiple tumour types; therefore, targeting hypoxia could have a broad therapeutic benefit. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

    PubMed

    Balasch, J; Vidal, E; Peñarrubia, J; Casamitjana, R; Carmona, F; Creus, M; Fábregues, F; Vanrell, J A

    2001-08-01

    It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values. Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation.

  13. STEADY STATE FLAMMABLE GAS RELEASE RATE CALCULATION AND LOWER FLAMMABILITY LEVEL EVALUATION FOR HANFORD TANK WASTE

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

    HU TA

    2009-10-26

    Assess the steady-state flammability level at normal and off-normal ventilation conditions. The hydrogen generation rate was calculated for 177 tanks using the rate equation model. Flammability calculations based on hydrogen, ammonia, and methane were performed for 177 tanks for various scenarios.

  14. Prediction of the efficacy of immunotherapy by measuring the integrity of cell-free DNA in plasma in colorectal cancer.

    PubMed

    Kitahara, Masahiro; Hazama, Shoichi; Tsunedomi, Ryouichi; Takenouchi, Hiroko; Kanekiyo, Shinsuke; Inoue, Yuka; Nakajima, Masao; Tomochika, Shinobu; Tokuhisa, Yoshihiro; Iida, Michihisa; Sakamoto, Kazuhiko; Suzuki, Nobuaki; Takeda, Shigeru; Ueno, Tomio; Yamamoto, Shigeru; Yoshino, Shigefumi; Nagano, Hiroaki

    2016-12-01

    We previously reported a phase II study of a cancer vaccine using five novel peptides recognized by HLA-A*2402-restricted CTL in combination with oxaliplatin-containing chemotherapy (FXV study) as first-line therapy for patients with metastatic colorectal cancer and demonstrated the safety and promising potential of our five-peptide cocktail. The objective of this analysis was to identify predictive biomarkers for identifying patients who are likely to receive a clinical benefit from immunochemotherapy. Circulating cell-free DNA (cfDNA) in plasma has been reported to be a candidate molecular biomarker for the efficacy of anticancer therapy. Unlike uniformly truncated small-sized DNA released from apoptotic normal cells, DNA released from necrotic cancer cells varies in size. The integrity of plasma cfDNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cfDNA), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cfDNA levels and integrity were analyzed by semi-quantitative real-time PCR. Progression-free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value (P = 0.0027). Surprisingly, in the HLA-A*2402-matched group, patients with a low plasma cfDNA integrity value had significantly better progression-free survival than those with a high value (P = 0.0015). This difference was not observed in the HLA-A*2402-unmatched group. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  15. Controlled release of isoproturon, imidacloprid, and cyromazine from alginate-bentonite-activated carbon formulations.

    PubMed

    Garrido-Herrera, F J; Gonzalez-Pradas, E; Fernandez-Pérez, M

    2006-12-27

    Different alginate-based systems of isoproturon, imidacloprid, and cyromazine have been investigated in order to obtain controlled release (CR) properties. The basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was modified using different amounts of bentonite and activated carbon. The higher values of encapsulation efficiency corresponded to those formulations prepared with higher percentages of activated carbon, showing higher encapsulation efficiency values for isoproturon and imidacloprid than for cyromazine, which has a higher water solubility. The kinetic experiments of imidacloprid/isoproturon release in water have shown us that the release rate is higher in imidacloprid systems than in those prepared with isoproturon. Moreover, it can be deduced that the use of bentonite and/or activated carbon sorbents reduces the release rate of the isoproturon and imidacloprid in comparison with the technical product and with alginate formulation without modifying agents. The highest decrease in release rate corresponds to the formulations prepared with the highest percentage of activated carbon. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T50, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the pesticide release data, the release of isoproturon and imidacloprid from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents and the permeability of the formulations were the most important factors modulating pesticide release. Finally, a linear correlation of the T50 values and the content of activated carbon in formulations were obtained.

  16. Chemosterilization of the sea lamprey (Petromyzon marinus)

    USGS Publications Warehouse

    Hanson, Lee H.; Manion, Patrick J.

    1978-01-01

    The chemical, P,P-bis(1-aziridinyl)-N-methylphosphinothioic amide (bisazir), was found in laboratory studies to be an effective sterilant for both sexes of adult sea lampreys (Petromyzon marinus) when given intraperitoneally at a dosage of 100 mg per kilogram of body weight. A total of 300 normal spawning-run sea lampreys and 300 injected with bisazir were released into the Big Garlic River, Marquette County, Michigan, (a small stream divided into five sections by natural barriers), to determine the effect of bisazir on the nesting and spawning behavior of the adults and on the production of larvae. The lampreys constructed and spawned in 95 nests. Sterile adults showed no abnormal nest building or spawning behavior. Sterile males competed effectively with normal males for females. Egg samples taken from nests indicated that eggs in nests where sterile males spawned with sterile or normal females did not hatch, although some embryonic development occurred. Extensive surveys with electric shockers produced no larvae in stream sections where sterile males spawned, but yielded numerous larvae in sections where normal males spawned with normal females. These findings suggest that the release of sterile males may be an effective tool in an integrated approach to control of sea lampreys in the Great Lakes.

  17. Smart drug release systems based on stimuli-responsive polymers.

    PubMed

    Qing, Guangyan; Li, Minmin; Deng, Lijing; Lv, Ziyu; Ding, Peng; Sun, Taolei

    2013-07-01

    Stimuli-responsive polymers could respond to external stimuli, such as temperature, pH, photo-irradiation, electric field, biomolecules in solution, etc., which further induce reversible transformations in the structures and conformations of polymers, providing an excellent platform for controllable drug release, while the accuracy of drug delivery could obtain obvious improvement in this system. In this review, recent progresses in the drug release systems based on stimuli-responsive polymers are summarized, in which drugs can be released in an intelligent mode with high accuracy and efficiency, while potential damages to normal cells and tissues can also be effectively prevented owing to the unique characteristics of materials. Moreover, we introduce some smart nanoparticles-polymers conjugates and drug release devices, which are especially suitable for the long-term sustained drug release.

  18. The effect of diphenylhydantoin on metabolic and growth hormone changes during and after exercise.

    PubMed Central

    Chalmers, R J; Johnson, R H

    1983-01-01

    Metabolic and human growth hormone responses to exercise were investigated in six normal healthy subjects on two occasions with and without an oral dose of diphenylhydantoin (500 mg). Serum diphenylhydantoin concentrations were similar in all subjects and were just below the accepted therapeutic range for epileptic patients. There was no significant difference in blood lactate, pyruvate or glucose concentrations with diphenylhydantoin. Plasma free fatty acids, and blood glycerol and total ketone concentrations were greater after exercise following diphenylhydantoin. Significantly greater concentrations of human growth hormone occurred during exercise with diphenylhydantoin. Further investigation of the mechanisms by which diphenylhydantoin alters lipolysis and human growth hormone release would be of value as these metabolic and hormonal effects could influence exercise tolerance in athletics and other pursuits. PMID:6886706

  19. Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

    PubMed Central

    Zorov, Dmitry B.; Juhaszova, Magdalena; Sollott, Steven J.

    2014-01-01

    Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo. PMID:24987008

  20. Partial hypopituitarism and Langerhans cell histiocytosis

    PubMed Central

    Balaguruswamy, S; Chattington, P D

    2011-01-01

    A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

  1. Pseudotumour Cerebri Presentation in a Child Under the Gonadotropin-Releasing Hormone Agonist Treatment

    PubMed Central

    Gül, Ülkü; Kaçar Bayram, Ayşe; Kendirci, Mustafa; Hatipoğlu, Nihal; Okdemir, Deniz; Gümüş, Hakan; Kurtoğlu, Selim

    2016-01-01

    Gonadotropin-releasing hormone analogues are common treatment option in central precocious puberty in childhood as well as in endometriosis, infertility, and prostate cancer in adults. Pseudotumor cerebri is a rare side effect observed in adults. We present the case of a girl with precocious puberty treated with triptorelin acetate who developed pseudotumor cerebri after the 4th dose. She had headaches, and her blood pressure was detected to be above the 99 percentile. There were no causes underlying of hypertension such as cardiac, renal, or endocrine. Neurological examination was normal except bilateral papilledema. Cranial magnetic resonance imaging was normal. Cerebrospinal fluid (CSF) opening pressure was elevated. Triptorelin therapy was ceased and acetazolamide was applied; CSF pressure returned to normal. We observed pseudotumor cerebri after precocious puberty treatment, a finding for the first time ever seen in childhood. PMID:27087351

  2. Investigations of magnesium, histamine and immunoglobulins dynamics in acute urticaria.

    PubMed

    Mureşan, D; Oană, A; Nicolae, I; Alecu, M; Moşescu, L; Benea, V; Flueraş, M

    1990-01-01

    In 42 urticaria patients, magnesium, histamine and IgE were dosed. Magnesium, IgE and histamine variations were followed in urticaria evolution, during acute phase and clinical remission. We noticed magnesium, histamine, IgE values variations depending on disease evolution and applied therapeutic scheme. Therefore: At disease starting point, histamine presented 3.5 times higher values than the normal ones. The value decreases following a curve which tends to reach normal values during clinical remission. At disease starting point, magnesium presented values under the inferior limit of the normal, 0.5 m mol/L respectively, as a mean. The value increases towards the normal limit during clinical remission. Immunoglobulins E follow a similar curve to histamine one, presenting 1,250 U/L values at the starting point, that, under medication, influence decrease between normal limits (800 U/L), during clinical remission. Analyzing the variations of biochemical parameters, the authors emphasize magnesium substitution treatment in urticaria.

  3. 19 CFR 351.408 - Calculation of normal value of merchandise from nonmarket economy countries.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Calculation of normal value of merchandise from nonmarket economy countries. 351.408 Section 351.408 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Calculation of Export Price, Constructed Export Price, Fair Value, and Normal Value §...

  4. 7 CFR 4287.113 - Release of collateral.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Loans § 4287.113 Release of collateral. (a) All releases of collateral with a value exceeding $100,000... loan. The Agency may, at its discretion, require an appraisal of the remaining collateral in cases... (a) of this section, lenders may, over the life of the loan, release collateral (other than personal...

  5. 19 CFR 162.44 - Release on payment of appraised value.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Release on payment of appraised value. 162.44 Section 162.44 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Treatment of Seized Merchandise § 162...

  6. Acoustical study of the development of stop consonants in children

    NASA Astrophysics Data System (ADS)

    Imbrie, Annika K.

    2003-10-01

    This study focuses on the acoustic patterns of stop consonants and adjacent vowels as they develop in young children (ages 26-33) over a six month period. The acoustic properties that are being measured for stop consonants include spectra of bursts, frication noise and aspiration noise, and formant movements. Additionally, acoustic landmarks are labeled for measurements of durations of events determined by these landmarks. These acoustic measurements are being interpreted in terms of the supraglottal, laryngeal, and respiratory actions that give rise to them. Preliminary data show that some details of the child's gestures are still far from achieving the adult pattern. The burst of frication noise at the release tends to be shorter than adult values, and often consists of multiple bursts. From the burst spectrum, the place of articulation appears to be normal. Finally, coordination of closure of the glottis and release of the primary articulator is still quite variable, as is apparent from a large standard deviation in VOT. Analysis of longitudinal data on young children will result in better models of the development of the coordination of articulation, phonation, and respiration for motor speech production. [Work supported by NIH Grants Nos. DC00038 and DC00075.

  7. Acoustical study of the development of stop consonants in children

    NASA Astrophysics Data System (ADS)

    Imbrie, Annika K.

    2004-05-01

    This study focuses on the acoustic patterns of stop consonants and adjacent vowels as they develop in young children (ages 2.6-3.3) over a 6-month period. The acoustic properties that are being measured for stop consonants include spectra of bursts, frication noise and aspiration noise, and formant movements. Additionally, acoustic landmarks are labeled for measurements of durations of events determined by these landmarks. These acoustic measurements are being interpreted in terms of the supraglottal, laryngeal, and respiratory actions that give rise to them. Preliminary data show that some details of the child's gestures are still far from achieving the adult pattern. The burst of frication noise at the release tends to be shorter than adult values, and often consists of multiple bursts, possibly due to greater compliance of the active articulator. From the burst spectrum, the place of articulation appears to be normal. Finally, coordination of closure of the glottis and release of the primary articulator is still quite variable, as is apparent from a large standard deviation in VOT. Analysis of longitudinal data on young children will result in better models of the development of motor speech production. [Work supported by NIH Grants DC00038 and DC00075.

  8. Biomarkers for wound healing and their evaluation.

    PubMed

    Patel, S; Maheshwari, A; Chandra, A

    2016-01-01

    A biological marker (biomarker) is a substance used as an indicator of biological state. Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Research has identified several cellular events and mediators associated with wound healing that can serve as biomarkers. Macrophages, neutrophils, fibroblasts and platelets release cytokines molecules including TNF-α, interleukins (ILs) and growth factors, of which platelet-derived growth factor (PDGF) holds the greatest importance. As a result, various white cells and connective tissue cells release both matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Studies have demonstrated that IL-1, IL-6, and MMPs, levels above normal, and an abnormally high MMP/TIMP ratio are often present in non-healing wounds. Clinical examination of wounds for these mediators could predict which wounds will heal and which will not, suggesting use of these chemicals as biomarkers of wound healing. There is also evidence that the application of growth factors like PDGF will alleviate the recuperating process of chronic, non-healing wounds. Finding a specific biomarker for wound healing status would be a breakthrough in this field and helping treat impaired wound healing.

  9. Preparation and characteristics of thermoresponsive gel of minocycline hydrochloride and evaluation of its effect on experimental periodontitis models.

    PubMed

    Ruan, Hong; Yu, Youcheng; Liu, Yun; Ding, Xiaojun; Guo, Xuehua; Jiang, Qian

    2016-01-01

    In this study, a thermoresponsive gel for minocycline (MCL) with chitosan/β-glycerophosphate (C/β-GP) was formulated and its characterization, in vitro release, stability, toxicity and pharmacodynamics were investigated. The formulation containing MCL was prepared by pouring the chitosan solution directly onto the sterilized drug powder and stirring before mixing with the β-glycerophosphate (β-GP) solution. The final preparations contained 0.5% (w/v) chitosan, 1.8% (w/v) β-GP and 2% (w/v) MCL. The drug content of prepared gels was in the range of 92-99%, and the pH value of the optimized formulation was found to be 5.6-6.2. The gelation temperature of the prepared C/β-GP thermogelling solutions was 37 °C. Color, consistency, pH, viscosity and drug content of the in situ gels were found to be consistent, and no signs of separation and deterioration were observed over a period of 90 d. In vivo studies showed that rats' liver and kidney tissue sections were normal, with no structural damage. The constituents of the in situ gels formulation had a well-sustained release efficacy on the animal model of periodontitis.

  10. Problems associated with the use of immediately dangerous to life and health (IDLH) values for estimating the hazard of accidental chemical releases.

    PubMed

    Alexeeff, G V; Lipsett, M J; Kizer, K W

    1989-11-01

    The possibility of accidental industrial chemical releases has generated considerable recent attention. One area requiring research for emergency planning is the development of safe exposure concentrations for the public in the event of an inadvertent release. The United States Environmental Protection Agency (EPA) has established a list of extremely hazardous substances and suggested that the toxicity ranking for 92 hazardous materials could be based on the "immediately dangerous to life or health" (IDLH) values developed by the National Institute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration (OSHA). Eighty-four compounds with IDLH values for which published toxicologic data were available were reviewed to assess the appropriateness of applying such values to accidental release situations. When compared with 30-min animal median lethal concentrations (LC50s), 18 of the IDLHs reviewed were in the same range as lethal levels for animals. For 45 compounds the IDLH values were comparable to concentrations producing severe toxic effects (specifically, unconsciousness, incapacitation, or intolerable irritation). Where available, emergency planning guidelines for the military were compared to IDLHs, and in all 31 cases, the IDLHs exceeded the military exposure guidelines. Twenty compounds also were found to pose a potential cancer risk according to common regulatory guidelines, even under the assumption of a single, 30-min exposure at the IDLH concentration. In addition, the high degree of variability (four orders of magnitude) in the relationship of IDLH values to outcomes of lethality or severe toxicity suggests that the use of IDLH values as emergency planning guidelines for accidental releases is questionable.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Calcium released by photolysis of DM-nitrophen stimulates transmitter release at squid giant synapse.

    PubMed

    Delaney, K R; Zucker, R S

    1990-07-01

    1. Transmitter release at the squid giant synapse was stimulated by photolytic release of Ca2+ from the 'caged' Ca2+ compound DM-nitrophen (Kaplan & Ellis-Davies, 1988) inserted into presynaptic terminals. 2. Competing binding reactions cause the amount of Ca2+ released by DM-nitrophen photolysis to depend on the concentrations of DM-nitrophen, total Ca2+, Mg+, ATP and native cytoplasmic Ca2+ buffer. Measurements of presynaptic [Ca2+] changes by co-injection of the fluorescent indicator dye Fura-2 show that DM-nitrophen photolysis causes a transient rise in Ca2+ followed by decay within about 150 ms to an increased steady-state level. 3. Rapid photolysis of Ca2(+)-loaded nitrophen within the presynaptic terminal was followed in less than a millisecond by depolarization of the postsynaptic membrane. As with action potential-evoked excitatory postsynaptic potentials (EPSPs), the light-evoked response was partially and reversibly blocked by 1-3 mM-kainic acid which desensitizes postsynaptic glutamate receptors. 4. Release was similar in magnitude and rate to normal action potential-mediated EPSPs. 5. The release of transmitter by photolysis of Ca2(+)-loaded DM-nitrophen was not affected by removal of Ca2+ from the saline or addition of tetrodotoxin. Photolysis of DM-nitrophen injected into presynaptic terminals without added Ca2+ did not stimulate release of transmitter nor did it interfere with normal action potential-mediated release. 6. Stimulation of presynaptic action potentials in Ca2(+)-free saline during the light-evoked response did not elicit increased release of transmitter if the ganglion was bathed in Ca2(+)-free saline, i.e. in the absence of Ca2+ influx. Increasing the intensity of the light or stimulating presynaptic action potentials in Ca2(+)-containing saline increased the release of transmitter. Therefore the failure of presynaptic voltage change to increase transmitter release resulting from release of caged Ca2+ was not due to saturation or inhibition of the release mechanism by light-released Ca2+. 7. Decreasing the temperature of the preparation increased the delay to onset of the light-evoked response and reduced its amplitude and rate of rise to an extent similar to that observed for action potential-evoked EPSPs.

  12. Dynamic Divisive Normalization Predicts Time-Varying Value Coding in Decision-Related Circuits

    PubMed Central

    LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W.

    2014-01-01

    Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding. PMID:25429145

  13. Comparison of diffusion-weighted MRI acquisition techniques for normal pancreas at 3.0 Tesla.

    PubMed

    Yao, Xiu-Zhong; Kuang, Tiantao; Wu, Li; Feng, Hao; Liu, Hao; Cheng, Wei-Zhong; Rao, Sheng-Xiang; Wang, He; Zeng, Meng-Su

    2014-01-01

    We aimed to optimize diffusion-weighted imaging (DWI) acquisitions for normal pancreas at 3.0 Tesla. Thirty healthy volunteers were examined using four DWI acquisition techniques with b values of 0 and 600 s/mm2 at 3.0 Tesla, including breath-hold DWI, respiratory-triggered DWI, respiratory-triggered DWI with inversion recovery (IR), and free-breathing DWI with IR. Artifacts, signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) of normal pancreas were statistically evaluated among different DWI acquisitions. Statistical differences were noticed in artifacts, SNR, and ADC values of normal pancreas among different DWI acquisitions by ANOVA (P <0.001). Normal pancreas imaging had the lowest artifact in respiratory-triggered DWI with IR, the highest SNR in respiratory-triggered DWI, and the highest ADC value in free-breathing DWI with IR. The head, body, and tail of normal pancreas had statistically different ADC values on each DWI acquisition by ANOVA (P < 0.05). The highest image quality for normal pancreas was obtained using respiratory-triggered DWI with IR. Normal pancreas displayed inhomogeneous ADC values along the head, body, and tail structures.

  14. 28 CFR Appendix A to Part 79 - FVC and FEV-1 Lower Limits of Normal Values

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false FVC and FEV-1 Lower Limits of Normal... RADIATION EXPOSURE COMPENSATION ACT Pt. 79, App. A Appendix A to Part 79—FVC and FEV-1 Lower Limits of Normal Values Table 1—Caucasian Males FVC Lower Limit of Normal Values, Hankinson, et al. (1999...

  15. Optimization, in vitro release and bioavailability of gamma-oryzanol-loaded calcium pectinate microparticles reinforced with chitosan.

    PubMed

    Kim, Jong Soo; Lee, Ji-Soo; Chang, Pahn-Shick; Lee, Hyeon Gyu

    2010-09-30

    Response surface methodology was used to optimize coating conditions, including chitosan concentration (X(1)) and coating time (X(2)), for sustained release of chitosan-coated Ca-pectinate (CP) microparticles containing oryzanol (OZ). The optimized values of X(1) and X(2) were found to be 1.48% and 69.92 min, respectively. These optimized values agreed favorably with the predicted results, indicating the utility of predictive models for the release of OZ in simulated intestinal fluid. In vitro release studies revealed that the chitosan-coated CP microparticles were quite stable under acidic conditions, but swell and disintegrate under alkaline conditions. In vivo release study of OZ, physically entrapped within chitosan-coated CP microcapsules, demonstrated the sustained release of OZ and could be used to improve the bioavailability of OZ following oral administration. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Phosphatidylinositol 3-kinase inhibition restores Ca2+ release defects and prolongs survival in myotubularin-deficient mice

    PubMed Central

    Kutchukian, Candice; Lo Scrudato, Mirella; Tourneur, Yves; Poulard, Karine; Vignaud, Alban; Berthier, Christine; Allard, Bruno; Lawlor, Michael W.; Buj-Bello, Ana; Jacquemond, Vincent

    2016-01-01

    Mutations in the gene encoding the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for a pediatric disease of skeletal muscle named myotubular myopathy (XLMTM). Muscle fibers from MTM1-deficient mice present defects in excitation–contraction (EC) coupling likely responsible for the disease-associated fatal muscle weakness. However, the mechanism leading to EC coupling failure remains unclear. During normal skeletal muscle EC coupling, transverse (t) tubule depolarization triggers sarcoplasmic reticulum (SR) Ca2+ release through ryanodine receptor channels gated by conformational coupling with the t-tubule voltage-sensing dihydropyridine receptors. We report that MTM1 deficiency is associated with a 60% depression of global SR Ca2+ release over the full range of voltage sensitivity of EC coupling. SR Ca2+ release in the diseased fibers is also slower than in normal fibers, or delayed following voltage activation, consistent with the contribution of Ca2+-gated ryanodine receptors to EC coupling. In addition, we found that SR Ca2+ release is spatially heterogeneous within myotubularin-deficient muscle fibers, with focally defective areas recapitulating the global alterations. Importantly, we found that pharmacological inhibition of phosphatidylinositol 3-kinase (PtdIns 3-kinase) activity rescues the Ca2+ release defects in isolated muscle fibers and increases the lifespan and mobility of XLMTM mice, providing proof of concept for the use of PtdIns 3-kinase inhibitors in myotubular myopathy and suggesting that unbalanced PtdIns 3-kinase activity plays a critical role in the pathological process. PMID:27911767

  17. Contact Quotient of Female Singers Singing Four Pitches for Five Vowels in Normal and Pressed Phonations.

    PubMed

    Ong Tan, Kendrich Graemer

    2017-09-01

    The present study aimed to investigate the contact quotient (CQ) values of breathy, normal, and pressed phonation types in four different sections of the female singing range. Electroglottography (EGG) and acoustic signals were recorded from 10 female singing teachers. Five vowels were sung for 1-3 seconds each, in three phonation types-normal, breathy, and pressed, in four pitches representing registration change points in the singing range. CQ values were automatically generated from the EGG signal using VoceVista at 35% threshold level. Sound pressure levels were checked in Praat. Unianova and correlations were performed using an SPSS program. CQ values of female participants in the study yielded ranges of 0.25-0.62 in normal and 0.34-0.73 in pressed. Normal and pressed CQ differed significantly from each other at P < 0.00. Breathy samples were not viable for analysis. A concentration of CQ values from 0.5 to 0.6 of both pressed low and pressed break samples was noted, but CQ values across the pitch range showed no significant trend. Normal and pressed phonation CQ values beyond the speaking pitch varied among the subjects. Pressed phonation CQ values were mostly higher, but the values were only relative to the corresponding normal phonation on the same pitch. Other measurements may be more suitable for measuring vocal fold impact stress in higher frequencies, thus, distinguishing normal from pressed singing. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  18. Acute turpentine inflammation and kinin release in rat-paw thermic oedema.

    PubMed Central

    Limãos, E. A.; Borges, D. R.; Souza-Pinto, J. C.; Gordon, A. H.; Prado, J. L.

    1981-01-01

    Livers from rats at 2-3 days after s.c. injection of turpentine, when perfused, synthesized prekallikrein nearly 3 times faster than did livers from normal rats. On the other hand paw oedema, produced by heating to 46 degrees, in rats injured in this way was less marked. Likewise in such rats the amount of bradykinin release by 50 min. of coaxial perfusion of the paw was only 13.6 +/- 4.6 compared with 63.1 +/- 13.4 ng in normal rats. A possible explanation for the observed reduction in production of bradykinin may be inhibition of kallikrein due to an increased concentration of alpha 2-macroglobulin. PMID:6173056

  19. On the mechanism of tachyphylaxis to tyramine in the isolated rat heart

    PubMed Central

    Axelrod, J.; Gordon, Edna; Hertting, G.; Kopin, I. J.; Potter, L. T.

    1962-01-01

    Tyramine was shown to release [3H]-catecholamines from an isolated rat heart previously perfused with [3H]-noradrenaline. With successive injections of tyramine the amount of [3H]-catecholamine released fell progressively and there was a parallel decrease in the increment of amplitude and rate of contraction of the heart. Reserpinized hearts were shown to take up less [3H]-noradrenaline than normal hearts. Release of radioactivity and loss of responsiveness to tyramine occurred more rapidly in the reserpinized heart. In the same preparation the uptake of [14C]-tyramine exceeded the quantity of the noradrenaline released. ImagesFig. 4 PMID:13863453

  20. Versatile solid-state relay

    NASA Technical Reports Server (NTRS)

    Fox, D. A.

    1977-01-01

    Solid-state relay (SSR), containing multinode control logic, is operated as normally open, normally closed, or latched. Moreover several can be paralleled to form two-pole or double-throw relays. Versatile unit ends need to design custom control circuit for every relay application. Technique can be extended to incorporate selectable time delay, on operation or release, or pulsed output.

  1. Triggered intracellular calcium waves in dog and human left atrial myocytes from normal and failing hearts.

    PubMed

    Aistrup, Gary L; Arora, Rishi; Grubb, Søren; Yoo, Shin; Toren, Benjamin; Kumar, Manvinder; Kunamalla, Aaron; Marszalec, William; Motiwala, Tej; Tai, Shannon; Yamakawa, Sean; Yerrabolu, Satya; Alvarado, Francisco J; Valdivia, Hector H; Cordeiro, Jonathan M; Shiferaw, Yohannes; Wasserstrom, John Andrew

    2017-11-01

    Abnormal intracellular Ca2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca2+ waves in left atria from normal and failing dog hearts. Intracellular Ca2+ cycling was studied using confocal microscopy during rapid pacing of atrial myocytes (36 °C) isolated from normal and failing canine hearts (ventricular tachypacing model). In normal atrial myocytes (NAMs), Ca2+ waves developed during rapid pacing at rates ≥ 3.3 Hz and immediately disappeared upon cessation of pacing despite high sarcoplasmic reticulum (SR) load. In heart failure atrial myocytes (HFAMs), triggered Ca2+ waves (TCWs) developed at a higher incidence at slower rates. Because of their timing, TCW development relies upon action potential (AP)-evoked Ca2+ entry. The distribution of Ca2+ wave latencies indicated two populations of waves, with early events representing TCWs and late events representing conventional spontaneous Ca2+ waves. Latency analysis also demonstrated that TCWs arise after junctional Ca2+ release has occurred and spread to non-junctional (cell core) SR. TCWs also occurred in intact dog atrium and in myocytes from humans and pigs. β-adrenergic stimulation increased Ca2+ release and abolished TCWs in NAMs but was ineffective in HFAMs making this a potentially effective adaptive mechanism in normals but potentially arrhythmogenic in HF. Block of Ca-calmodulin kinase II also abolished TCWs, suggesting a role in TCW formation. Pharmacological manoeuvres that increased Ca2+ release suppressed TCWs as did interventions that decreased Ca2+ release but these also severely reduced excitation-contraction coupling. TCWs develop during the atrial AP and thus could affect AP duration, producing repolarization gradients and creating a substrate for reentry, particularly in HF where they develop at slower rates and a higher incidence. TCWs may represent a mechanism for the initiation of atrial fibrillation particularly in HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

  2. Widespread arsenic contamination of soils in residential areas and public spaces: an emerging regulatory or medical crisis?

    PubMed

    Belluck, D A; Benjamin, S L; Baveye, P; Sampson, J; Johnson, B

    2003-01-01

    A critical review finds government agencies allow, permit, license, or ignore arsenic releases to surface soils. Release rates are controlled or evaluated using risk-based soil contaminant numerical limits employing standardized risk algorithms, chemical-specific and default input values. United States arsenic residential soil limits, approximately 0.4- approximately 40 ppm, generally correspond to a one-in-one-million to a one-in-ten-thousand incremental cancer risk range via ingestion of or direct contact with contaminated residential soils. Background arsenic surface soil levels often exceed applicable limits. Arsenic releases to surface soils (via, e.g., air emissions, waste recycling, soil amendments, direct pesticide application, and chromated copper arsenic (CCA)-treated wood) can result in greatly elevated arsenic levels, sometimes one to two orders of magnitude greater than applicable numerical limits. CCA-treated wood, a heavily used infrastructure material at residences and public spaces, can release sufficient arsenic to result in surface soil concentrations that exceed numerical limits by one or two orders of magnitude. Although significant exceedence of arsenic surface soil numerical limits would normally result in regulatory actions at industrial or hazardous waste sites, no such pattern is seen at residential and public spaces. Given the current risk assessment paradigm, measured or expected elevated surface soil arsenic levels at residential and public spaces suggest that a regulatory health crisis of sizeable magnitude is imminent. In contrast, available literature and a survey of government agencies conducted for this paper finds no verified cases of human morbidity or mortality resulting from exposure to elevated levels of arsenic in surface soils. This concomitance of an emerging regulatory health crisis in the absence of a medical crisis is arguably partly attributable to inadequate government and private party attention to the issue.

  3. 19 CFR 351.408 - Calculation of normal value of merchandise from nonmarket economy countries.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... nonmarket economy countries. 351.408 Section 351.408 Customs Duties INTERNATIONAL TRADE ADMINISTRATION... economy countries. (a) Introduction. In identifying dumping from a nonmarket economy country, the Secretary normally will calculate normal value by valuing the nonmarket economy producers' factors of...

  4. 19 CFR 351.408 - Calculation of normal value of merchandise from nonmarket economy countries.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... nonmarket economy countries. 351.408 Section 351.408 Customs Duties INTERNATIONAL TRADE ADMINISTRATION... economy countries. (a) Introduction. In identifying dumping from a nonmarket economy country, the Secretary normally will calculate normal value by valuing the nonmarket economy producers' factors of...

  5. 19 CFR 351.408 - Calculation of normal value of merchandise from nonmarket economy countries.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... nonmarket economy countries. 351.408 Section 351.408 Customs Duties INTERNATIONAL TRADE ADMINISTRATION... economy countries. (a) Introduction. In identifying dumping from a nonmarket economy country, the Secretary normally will calculate normal value by valuing the nonmarket economy producers' factors of...

  6. 19 CFR 351.408 - Calculation of normal value of merchandise from nonmarket economy countries.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... nonmarket economy countries. 351.408 Section 351.408 Customs Duties INTERNATIONAL TRADE ADMINISTRATION... economy countries. (a) Introduction. In identifying dumping from a nonmarket economy country, the Secretary normally will calculate normal value by valuing the nonmarket economy producers' factors of...

  7. Enhancing the Therapeutic Efficacy of Tamoxifen Citrate Loaded Span-Based Nano-Vesicles on Human Breast Adenocarcinoma Cells.

    PubMed

    Kassem, Mohammed A; Megahed, Mohamed A; Abu Elyazid, Sherif K; Abd-Allah, Fathy I; Abdelghany, Tamer M; Al-Abd, Ahmed M; El-Say, Khalid M

    2018-05-01

    Serious adverse effects and low selectivity to cancer cells are the main obstacles of long term therapy with Tamoxifen (Tmx). This study aimed to develop Tmx-loaded span-based nano-vesicles for delivery to malignant tissues with maximum efficacy. The effect of three variables on vesicle size (Y 1 ), zeta potential (Y 2 ), entrapment efficiency (Y 3 ) and the cumulative percent release after 24 h (Y 4 ) were optimized using Box-Behnken design. The optimized formula was prepared and tested for its stability in different storage conditions. The observed values for the optimized formula were 310.2 nm, - 42.09 mV, 75.45 and 71.70% for Y 1 , Y 2 , Y 3 , and Y 4 , respectively. The examination using electron microscopy confirmed the formation of rounded vesicles with distinctive bilayer structure. Moreover, the cytotoxic activity of the optimized formula on both breast cancer cells (MCF-7) and normal cells (BHK) showed enhanced selectivity (9.4 folds) on cancerous cells with IC 50 values 4.7 ± 1.5 and 44.3 ± 1.3 μg/ml on cancer and normal cells, respectively. While, free Tmx exhibited lower selectivity (2.5 folds) than optimized nano-vesicles on cancer cells with IC 50 values of 9.0 ± 1.1 μg/ml and 22.5 ± 5.3 μg/ml on MCF-7 and BHK cells, respectively. The promising prepared vesicular system, with greater efficacy and selectivity, provides a marvelous tool to overcome breast cancer treatment challenges.

  8. Minimal functional β-cell mass in intraportal implants that reduces glycemic variability in type 1 diabetic recipients.

    PubMed

    Gillard, Pieter; Hilbrands, Robert; Van de Velde, Ursule; Ling, Zhidong; Lee, Da Hae; Weets, Ilse; Gorus, Frans; De Block, Christophe; Kaufman, Leonard; Mathieu, Chantal; Pipeleers, Daniel; Keymeulen, Bart

    2013-11-01

    Previous work has shown a correlation between β-cell number in cultured islet cell grafts and their ability to induce C-peptide secretion after intraportal implantation in C-peptide-negative type1 diabetic patients. In this cross-sectional study, we examined the minimal functional β-cell mass (FBM) in the implant that induces metabolic improvement. Glucose clamps assessed FBM in 42 recipients with established implants. C-peptide release during each phase was expressed as percentage of healthy control values. Its relative magnitude during a second hyperglycemic phase was most discriminative and therefore selected as a parameter to be correlated with metabolic effects. Recipients with functioning β-cell implants exhibited average FBM corresponding to 18% of that in normal control subjects (interquartile range 10-33%). Its relative magnitude negatively correlated with HbA1c levels (r = -0.47), daily insulin dose (r = -0.75), and coefficient of variation of fasting glycemia (CVfg) (r = -0.78, retained in multivariate analysis). A correlation between FBM and CVfg <25% appeared from the receiver operating characteristic curve (0.97 [95% CI 0.93-1.00]). All patients with FBM >37% exhibited CVfg <25% and a >50% reduction of their pretransplant CVfg; this occurred in none with FBM <5%. Implants with FBM >18% reduced CVfg from a median pretransplant value of 46 to <25%. Glucose clamping assesses the degree of restoration in FBM achieved by islet cell implants. Values >37% of normal control subjects appear needed to reduce glycemic variability in type 1 diabetic recipients. Further studies should examine whether the test can help guide decisions on additional islet cell transplants and on adjusting or stopping immunotherapy.

  9. 38 CFR 36.4277 - Release of security.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... payment of the indebtedness the holder shall not release a lien or other right in or to property held as..., the holder shall not release a lien under paragraph (a) of this section unless the consideration... released it shall be the holder's duty to acquire such lien on property of substantially equal value which...

  10. USDA National Nutrient Database for Standard Reference, Release 24

    USDA-ARS?s Scientific Manuscript database

    The USDA Nutrient Database for Standard Reference, Release 24 contains data for over 7,900 food items for up to 146 food components. It replaces the previous release, SR23, issued in September 2010. Data in SR24 supersede values in the printed Handbooks and previous electronic releases of the databa...

  11. A novel platform designed by Au core/inorganic shell structure conjugated onto MTX/LDH for chemo-photothermal therapy.

    PubMed

    Tian, De-Ying; Wang, Wei-Yuan; Li, Shu-Ping; Li, Xiao-Dong; Sha, Zhao-Lin

    2016-05-30

    A novel platform making up of methotrexate intercalated layered double hydroxide (MTX/LDH) hybrid doped with gold nanoparticles (NPs) may have great potential both in chemo-photothermal therapy and the simultaneous drug delivery. In this paper, a promising platform of Au@PDDA-MTX/LDH was developed for anti-tumor drug delivery and synergistic therapy. Firstly, Au NPs were coated using Layer-by-Layer (LbL) technology by alternate deposition of poly (diallyldimethylammonium chloride) (PDDA) and MTX molecules, and then the resulting core-shell structures (named as Au@PDDA-MTX) were directly conjugated onto the surface of MTX/LDH hybrid by electrostatic attraction to afford Au@PDDA-MTX/LDH NPs. Here MTX was used as both the agent for surface modification and the anti-tumor drug for chemotherapy. The platform of Au@PDDA-MTX/LDH NPs not only had a high drug-loading capacity, but also showed excellent colloidal stability and interesting pH-responsive release profile. In vitro drug release studies demonstrated that MTX released from Au@PDDA-MTX/LDH was relatively slow under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. Furthermore, the combined treatment of cancer cells by using Au@PDDA-MTX/LDH for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of the platform for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Flare Energy Release: Internal Conflict, Contradiction with High Resolution Observations, Possible Solutions

    NASA Astrophysics Data System (ADS)

    Pustilnik, L.

    2017-06-01

    All accepted paradigm of solar and stellar flares energy release based on 2 whales: 1. Source of energy is free energy of non-potential force free magnetic field in atmosphere above active region; 2. Process of ultrafast dissipation of magnetic fields is Reconnection in Thin Turbulent Current Sheet (RTTCS). Progress in observational techniques in last years provided ultra-high spatial resolution and in physics of turbulent plasma showed that real situation is much more complicated and standard approach is in contradiction both with observations and with problem of RTTCS stability. We present critical analysis of classic models of pre-flare energy accumulation and its dissipation during flare energy release from pioneer works Giovanelli (1939, 1947) up to topological reconnection. We show that all accepted description of global force-free fields as source of future flare cannot be agreed with discovered in last years fine and ultra-fine current-magnetic structure included numerouse arcs-threads with diameters up to 100 km with constant sequence from photosphere to corona. This magnetic skeleton of thin current magnetic threads with strong interaction between them is main source of reserved magnetic energy insolar atmosphere. Its dynamics will be controlled by percolation of magnetic stresses through network of current-magnetic threads with transition to flare state caused by critical value of global current. We show that thin turbulent current sheet is absolutely unstable configuration both caused by splitting to numerous linear currents by dissipative modes like to tearing, and as sequence of suppress of plasma turbulence caused by anomalous heating of turbulent plasma. In result of these factors primary RTTCS will be disrupted in numerous turbulent and normal plasma domains like to resistors network. Current propagation through this network will have percolation character with all accompanied properties of percolated systems: self-organization with formation power spectrum of distribution of flares and micro-flares, and possibility of phase transition to flare energy release with huge increasing of energy release.

  13. Dynamic measurement of the calcium buffering properties of the sarcoplasmic reticulum in mouse skeletal muscle.

    PubMed

    Manno, Carlo; Sztretye, Monika; Figueroa, Lourdes; Allen, Paul D; Ríos, Eduardo

    2013-01-15

    The buffering power, B, of the sarcoplasmic reticulum (SR), ratio of the changes in total and free [Ca(2+)], was determined in fast-twitch mouse muscle cells subjected to depleting membrane depolarization. Changes in total SR [Ca(2+)] were measured integrating Ca(2+) release flux, determined with a cytosolic [Ca(2+)] monitor. Free [Ca(2+)](SR) was measured using the cameleon D4cpv-Casq1. In 34 wild-type (WT) cells average B during the depolarization (ON phase) was 157 (SEM 26), implying that of 157 ions released, 156 were bound inside the SR. B was significantly greater when BAPTA, which increases release flux, was present in the cytosol. B was greater early in the pulse - when flux was greatest - than at its end, and greater in the ON than in the OFF. In 29 Casq1-null cells, B was 40 (3.6). The difference suggests that 75% of the releasable calcium is normally bound to calsequestrin. In the nulls the difference in B between ON and OFF was less than in the WT but still significant. This difference and the associated decay in B during the ON were not artifacts of a slow SR monitor, as they were also found in the WT when [Ca(2+)](SR) was tracked with the fast dye fluo-5N. The calcium buffering power, binding capacity and non-linear binding properties of the SR measured here could be accounted for by calsequestrin at the concentration present in mammalian muscle, provided that its properties were substantially different from those found in solution. Its affinity should be higher, or K(D) lower than the conventionally accepted 1 mm; its cooperativity (n in a Hill fit) should be higher and the stoichiometry of binding should be at the higher end of the values derived in solution. The reduction in B during release might reflect changes in calsequestrin conformation upon calcium loss.

  14. Regional ADC values of the normal brain: differences due to age, gender, and laterality.

    PubMed

    Naganawa, Shinji; Sato, Kimihide; Katagiri, Toshio; Mimura, Takeo; Ishigaki, Takeo

    2003-01-01

    The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean+/-standard deviation 2.3+/-1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference.

  15. Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats.

    PubMed

    Imai, Hisanori; Misra, Gauri P; Wu, Linfeng; Janagam, Dileep R; Gardner, Thomas W; Lowe, Tao L

    2015-12-01

    Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia.

  16. Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats

    PubMed Central

    Imai, Hisanori; Misra, Gauri P.; Wu, Linfeng; Janagam, Dileep R.; Gardner, Thomas W.; Lowe, Tao L.

    2015-01-01

    Purpose Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. Methods The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. Results The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. Conclusions The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia. PMID:26658505

  17. Neonatal hydrocortisone therapy does not have a serious suppressive effect on the later function of the hypothalamus-pituitary-adrenal axis.

    PubMed

    Takayanagi, Toshimitsu; Matsuo, Koji; Egashira, Tomoko; Mizukami, Tomoko

    2015-05-01

    This study investigated whether providing extremely low birthweight (ELBW) infants with a large amount of hydrocortisone had a serious suppressive effect on the later function of the hypothalamus-pituitary-adrenal (HPA) axis. We evaluated the function of the HPA axis in 58 ELBW infants receiving 9.0 ± 7.2 mg/kg of intravenous and 68.1 ± 34.1 mg/kg of oral hydrocortisone using a human corticotropin-releasing hormone stimulation test. The mean age at investigation was 12.0 ± 5.2 months. The response was judged to be normal when the maximum to minimum ratio of the plasma adrenocorticotropic hormone (ACTH) concentration was >2, the peak value of the serum cortisol concentration was >552 nmol/L, or the increment was >193 nmol/L than baseline concentration. Of the 58 infants studied, 51 (88%) displayed a normal response to both the ACTH and cortisol secretion and seven infants (12%) who were judged to be poor responders exhibited a peak cortisol value of >386 nmol/L without any episode of adrenal insufficiency. Providing ELBW infants with a daily low dose of long-term hydrocortisone therapy should not lead to a serious suppressive effect on the later function of the HPA axis, regardless of the administration method. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  18. Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism.

    PubMed

    Giustina, A; Schettino, M; Bussi, A R; Legati, F; Licini, M; Zuccato, F; Wehrenberg, W B

    1992-01-01

    Patients with hyperthyroidism have reduced GH responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of arginine on GH secretion has been suggested to depend on a decrease in hypothalamic somatostatin tone. The aim of our study was to evaluate the effects of arginine on the GH-releasing hormone (GHRH)-stimulated GH secretion in patients with hyperthyroidism. Six hyperthyroid patients with recent diagnosis of Graves' disease [mean age +/- SEM, 39.2 +/- 1.4 years; body mass index (BMI) 22 +/- 0.4 kg/m2] and 6 healthy nonobese volunteers (4 males, 2 females; mean age +/- SEM, 35 +/- 3.5 years) underwent two experimental trials at no less than 7-day intervals: GHRH (100 micrograms, i.v.)-induced GH secretion was evaluated after 30 min i.v. infusion of saline (100 ml) or arginine (30 g) in 100 ml of saline. Hyperthyroid patients showed blunted GH peaks after GHRH (13.2 +/- 2.9 micrograms/l) as compared with normal subjects (23.8 +/- 3.9 micrograms/l, p < 0.05). GH peaks after GHRH were only slightly enhanced by arginine in hyperthyroid subjects (17.6 +/- 2.9 micrograms/l), whereas, in normal subjects, the enhancement was clear cut (36.6 +/- 4.4 micrograms/l; p < 0.05). GH values after arginine + GHRH were still lower in hyperthyroid patients with respect to normal subjects. Our data demonstrate that arginine enhances but does not normalize the GH response to GHRH in patients with hyperthyroidism when compared with normal subjects. We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level.

  19. Percutaneous release of the plantar fascia. New surgical procedure.

    PubMed

    Oliva, Francesco; Piccirilli, Eleonora; Tarantino, Umberto; Maffulli, Nicola

    2017-01-01

    Plantar fasciopathy presents with pain at the plantar and medial aspect of the heel. If chronic, it can negatively impact on quality of life. Plantar fasciopathy is not always self-limiting, and can be debilitating. Surgical management involves different procedures. We describe a percutaneous plantar fascia release. A minimally invasive access to the plantar tuberosity of the calcaneus is performed, and a small scalpel blade is used to release the fascia. With this procedure, skin healing problems, nerve injuries, infection and prolonged recovery time are minimised, allowing early return to normal activities. V.

  20. Protein C

    MedlinePlus

    ... Normal Results Normal values are 60% to 150% inhibition. Normal value ranges may vary slightly among different ... Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us ...

  1. Protein S

    MedlinePlus

    ... Normal Results Normal values are 60% to 150% inhibition. Normal value ranges may vary slightly among different ... Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us ...

  2. Normal references of right ventricular strain values by two-dimensional strain echocardiography according to the age and gender.

    PubMed

    Park, Jae-Hyeong; Choi, Jin-Oh; Park, Seung Woo; Cho, Goo-Yeong; Oh, Jin Kyung; Lee, Jae-Hwan; Seong, In-Whan

    2018-02-01

    Right ventricular (RV) strain values by 2-dimensional strain echocardiography (STE) can be used as objective markers of RV systolic function. However, there is little data about normal reference RV strain values according to age and gender. We measured normal RV strain values by STE. RV strain values were analyzed from the digitally stored echocardiographic images from NORMAL (Normal echOcardiogRaphic diMensions and functions in KoreAn popuLation) study for the measurement of normal echocardiographic values performed in 23 Korean university hospitals. We enrolled total 1003 healthy persons in the NORMAL study. Of them, we analyzed 2-dimensional RV strain values in 493 subjects (261 females, mean 47 ± 15 years old) only with echocardiographic images by GE machines. Their LV systolic and diastolic functions were normal. RV fractional area change was 48 ± 6% and tricuspid annular plane systolic excursion was 23 ± 3 mm. Total RV global longitudinal peak systolic strain (RVGLS total ) was -21.5 ± 3.2%. Females had higher absolute RVGLS total (-22.3 ± 3.3 vs -20.7 ± 2.9%, p < 0.001) than males. Younger (<50 years old) females had higher absolute RVGLS total (-22.9 ± 3.2 vs -20.5 ± 2.8%, p < 0.001) than age matched males. RVGLS total in females gradually increased according to age (p for trend = 0.002) and becomes almost similar in age ≥50 years. However, this trend was not seen in males (p for trend = 0.287), and younger males had similar RVGLS total value to that of older males (age ≥50 years, -20.5 ± 2.8 vs -20.9 ± 3.1%, p = 0.224). We calculated normal RVGLS values in normal population. Females have higher absolute strain values than males, especially in younger age groups (<50 years old).

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

    Kicker, Dwayne Curtis; Herrick, Courtney G; Zeitler, Todd

    The numerical code DRSPALL (from direct release spallings) is written to calculate the volume of Waste Isolation Pilot Plant solid waste subject to material failure and transport to the surface (i.e., spallings) as a result of a hypothetical future inadvertent drilling intrusion into the repository. An error in the implementation of the DRSPALL finite difference equations was discovered and documented in a software problem report in accordance with the quality assurance procedure for software requirements. This paper describes the corrections to DRSPALL and documents the impact of the new spallings data from the modified DRSPALL on previous performance assessment calculations.more » Updated performance assessments result in more simulations with spallings, which generally translates to an increase in spallings releases to the accessible environment. Total normalized radionuclide releases using the modified DRSPALL data were determined by forming the summation of releases across each potential release pathway, namely borehole cuttings and cavings releases, spallings releases, direct brine releases, and transport releases. Because spallings releases are not a major contributor to the total releases, the updated performance assessment calculations of overall mean complementary cumulative distribution functions for total releases are virtually unchanged. Therefore, the corrections to the spallings volume calculation did not impact Waste Isolation Pilot Plant performance assessment calculation results.« less

  4. Effect of Mg2+ on the control of Ca2+ release in skeletal muscle fibres of the toad.

    PubMed Central

    Lamb, G D; Stephenson, D G

    1991-01-01

    1. The effect of myoplasmic Mg2+ on Ca2+ release was examined in mechanically skinned skeletal muscle fibres, in which the normal voltage-sensor control of Ca2+ release is preserved. The voltage sensors could be activated by depolarizing the transverse tubular (T-) system by lowering the [K+] in the bathing solution. 2. Fibres spontaneously contracted when the free [Mg2+] was decreased from 1 to 0.05 mM, with no depolarization or change of total ATP, [Ca2+] or pH (pCa 6.7, 50 microM-EGTA). After such a 'low-Mg2+ response' the sarcoplasmic reticulum (SR) was depleted of Ca2+ and neither depolarization nor caffeine (2 mM) could induce a response, unless the [Mg2+] was raised and the SR reloaded with Ca2+. Exposure to 0.05 mM-Mg2+ at low [Ca2+] (2 mM-free EGTA, pCa greater than 8.7) also induced Ca2+ release and depleted the SR. 3. The response to low [Mg2+] was unaffected by inactivation of the voltage sensors, but was completely blocked by 2 microM-Ruthenium Red indicating that it involved Ca2+ efflux through the normal Ca2+ release channels. 4. In the absence of ATP (and creatine phosphate), complete removal of Mg2+ (i.e. no added Mg2+ with 1 mM-EDTA) did not induce Ca2+ release. Depolarization in the absence of Mg2+ and ATP also did not induce Ca2+ release. 5. Depolarization in 10 mM-Mg2+ (pCa 6.7, 50 microM-EGTA, 8 mM-total ATP) did not produce any response. In the presence of 1 mM-EGTA to chelate most of the released Ca2+, depolarizations in 10 mM-Mg2+ did not noticeably deplete the SR of Ca2+, whereas a single depolarization in 1 mM-Mg2+ (and 1 mM-EGTA) resulted in marked depletion. Depolarization in the presence of D600 and 10 mM-Mg2+ produced use-dependent 'paralysis', indicating that depolarization in 10 mM-Mg2+ did indeed activate the voltage sensors. 6. Depolarization in the presence of 10 mM-Mg2+ and 25 microM-ryanodine neither interfered with the normal voltage control of Ca2+ release nor caused depletion of the Ca2+ in the SR even after returning to 1 mM-Mg2+ for 1 min, indicating that few if any of the release channels had been opened by the depolarization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1708823

  5. Does a normal foetus really have a future of value? A reply to Marquis.

    PubMed

    Lovering, Robert P

    2005-04-01

    The traditional approach to the abortion debate revolves around numerous issues, such as whether the foetus is a person, whether the foetus has rights, and more. Don Marquis suggests that this traditional approach leads to a standoff and that the abortion debate 'requires a different strategy.' Hence his 'future of value' strategy, which is summarized as follows: (1) A normal foetus has a future of value. (2) Depriving a normal foetus of a future of value imposes a misfortune on it. (3) Imposing a misfortune on a normal foetus is prima facie wrong. (4) Therefore, depriving a normal foetus of a future of value is prima facie wrong. (5) Killing a normal foetus deprives it of a future value. (6) Therefore, killing a normal foetus is prima facie wrong. In this paper, I argue that Marquis's strategy is not different since it involves the concept of person--a concept deeply rooted in the traditional approach. Specifically, I argue that futures are valuable insofar as they are not only dominated by goods of consciousness, but are experienced by psychologically continuous persons. Moreover, I argue that his strategy is not sound since premise (1) is false. Specifically, I argue that a normal foetus, at least during the first trimester, is not a person. Thus, during that stage of development it is not capable of experiencing its future as a psychologically continuous person and, hence, it does not have a future of value.

  6. The sensitivity of the human thirst response to changes in plasma osmolality: a systematic review.

    PubMed

    Hughes, Fintan; Mythen, Monty; Montgomery, Hugh

    2018-01-01

    Dehydration is highly prevalent and is associated with adverse cardiovascular and renal events. Clinical assessment of dehydration lacks sensitivity. Perhaps a patient's thirst can provide an accurate guide to fluid therapy. This systematic review examines the sensitivity of thirst in responding to changes in plasma osmolality in participants of any age with no condition directly effecting their sense of thirst. Medline and EMBASE were searched up to June 2017. Inclusion criteria were all studies reporting the plasma osmolality threshold for the sensation of thirst. A total of 12 trials were included that assessed thirst intensity on a visual analogue scale, as a function of plasma osmolality (pOsm), and employed linear regression to define the thirst threshold. This included 167 participants, both healthy controls and those with a range of pathologies, with a mean age of 41 (20-78) years.The value ±95% CI for the pOsm threshold for thirst sensation was found to be 285.23 ± 1.29 mOsm/kg. Above this threshold, thirst intensity as a function of pOsm had a mean ± SEM slope of 0.54 ± 0.07 cm/mOsm/kg. The mean ± 95% CI vasopressin release threshold was very similar to that of thirst, being 284.3 ± 0.71 mOsm/kg.Heterogeneity across studies can be accounted for by subtle variation in experimental protocol and data handling. The thresholds for thirst activation and vasopressin release lie in the middle of the normal range of plasma osmolality. Thirst increases linearly as pOsm rises. Thus, osmotically balanced fluid administered as per a patient's sensation of thirst should result in a plasma osmolality within the normal range. This work received no funding.

  7. Dynamic divisive normalization predicts time-varying value coding in decision-related circuits.

    PubMed

    Louie, Kenway; LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W

    2014-11-26

    Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding. Copyright © 2014 the authors 0270-6474/14/3416046-12$15.00/0.

  8. Chemical durability and leaching mechanism of Ce0.5Eu0.5PO4 ceramics: Effects of temperature and pH values

    NASA Astrophysics Data System (ADS)

    Zhao, Xiaofeng; Teng, Yuancheng; Wu, Lang; Huang, Yi; Ma, Jiyan; Wang, Guolong

    2015-11-01

    Ce0.5Eu0.5PO4 ceramics with high relative density were prepared by hot-press (HPS) and pressureless (PLS) sintering. The effects of temperature and pH values on the chemical durability of the ceramics were investigated. The results show that an increase of acidity significantly accelerated the corrosion of the samples. In alkaline leachates, further release elements were prevented by the newborn surface precipitation. The leach rate (Rn) of HPS sample was similar to that of PLS specimen in deionized water, but higher Rn for PLS sample was found in pH = 11 solution. Moreover, apparent activation energy of the dissolution of Eu (40 ± 4 kJ mol-1) is much higher than that of Ce (20 ± 1 kJ mol-1), leading to the higher normalized elemental leach rate of Eu. Both the Eu and Ce elements have low leach rates (10-12-10-9 m d-1) after 42 days in all the leachates studied in this work.

  9. Salivary cortisol and cortisone in the clinical setting.

    PubMed

    Blair, Joanne; Adaway, Jo; Keevil, Brian; Ross, Richard

    2017-06-01

    A resurgence of interest in salivary biomarkers has generated evidence for their value in assessing adrenal function. The advantages of salivary measurements include only free hormone is detected, samples can be collected during normal daily routines and stress-induced cortisol release is less likely to occur than during venepuncture. We review the use of salivary biomarkers to diagnose and monitor patients for conditions of cortisol excess and deficiency and discuss the value of measuring salivary cortisone versus salivary cortisol. Developments in laboratory techniques have enabled the measurement of salivary hormones with a high level of sensitivity and specificity. In states of altered cortisol binding, salivary biomarkers are more accurate measures of adrenal reserve than serum cortisol. Salivary cortisone is a superior marker of serum cortisol compared with salivary cortisol, specifically when serum cortisol is low and during hydrocortisone therapy when contamination of saliva may result in misleading salivary cortisol concentrations. Salivary cortisol and cortisone can be used to assess cortisol excess, deficiency and hydrocortisone replacement, with salivary cortisone having the advantage of detection when serum cortisol levels are low and there is no interference from oral hydrocortisone.

  10. Water potential in excised leaf tissue: comparison of a commercial dew point hygrometer and a thermocouple psychrometer on soybean, wheat, and barley.

    PubMed

    Nelsen, C E; Safir, G R; Hanson, A D

    1978-01-01

    Leaf water potential (Psi(leaf)) determinations were made on excised leaf samples using a commercial dew point hygrometer (Wescor Inc., Logan, Utah) and a thermocouple psychrometer operated in the isopiestic mode. With soybean leaves (Glycine max L.), there was good agreement between instruments; equilibration times were 2 to 3 hours. With cereals (Triticum aestivum L. and Hordeum vulgare L.), agreement between instruments was poor for moderately wilted leaves when 7-mm-diameter punches were used in the hygrometer and 20-mm slices were used in the psychrometer, because the Psi(leaf) values from the dew point hygrometer were too high. Agreement was improved by replacing the 7-mm punch samples in the hygrometer by 13-mm slices, which had a lower cut edge to volume ratio. Equilibration times for cereals were normally 6 to 8 hours. Spuriously high Psi(leaf) values obtained with 7-mm leaf punches may be associated with the ion release and reabsorption that occur upon tissue excision; such errors evidently depend both on the species and on tissue water status.

  11. Diffuse Reflectance Spectroscopy: Getting the Capillary Refill Test Under One's Thumb.

    PubMed

    Henricson, Joakim; Toll John, Rani; Anderson, Chris D; Björk Wilhelms, Daniel

    2017-12-02

    The capillary refill test was introduced in 1947 to help estimate circulatory status in critically ill patients. Guidelines commonly state that refill should occur within 2 s after releasing 5 s of firm pressure (e.g., by the physician's finger) in the normal healthy supine patient. A slower refill time indicates poor skin perfusion, which can be caused by conditions including sepsis, blood loss, hypoperfusion, and hypothermia. Since its introduction, the clinical usefulness of the test has been debated. Advocates point out its feasibility and simplicity and claim that it can indicate changes in vascular status earlier than changes in vital signs such as heart rate. Critics, on the other hand, stress that the lack of standardization in how the test is performed and the highly subjective nature of the naked eye assessment, as well as the test's susceptibility to ambient factors, markedly lowers the clinical value. The aim of the present work is to describe in detail the course of the refill event and to suggest potentially more objective and exact endpoint values for the capillary refill test using diffuse polarization spectroscopy.

  12. Microiontophoretic release of drugs from micropipettes

    PubMed Central

    Clarke, G.; Hill, R. G.; Simmonds, M. A.

    1973-01-01

    1. The use of 24Na+ of high specific activity allowed its iontophoretic release from multibarrelled glass micropipettes to be followed over short periods with low currents. 2. When a negative retaining current was passed to reduce diffusional efflux between the periods of positive current expulsion of 24Na+, the rate of release of 24Na+ during the expulsion period progressively increased during the first minute before becoming constant. 3. The currents employed were similar to those normally used to regulate the microiontophoretic release of potent drugs such as γ-aminobutyric acid. It is therefore concluded that, during the usual period of response to such drugs, the rate of release of drug is not constant but increasing. 4. The implications of these observations for the construction of microiontophoretic dose-response relationships is discussed. PMID:4724187

  13. Univariate normalization of bispectrum using Hölder's inequality.

    PubMed

    Shahbazi, Forooz; Ewald, Arne; Nolte, Guido

    2014-08-15

    Considering that many biological systems including the brain are complex non-linear systems, suitable methods capable of detecting these non-linearities are required to study the dynamical properties of these systems. One of these tools is the third order cummulant or cross-bispectrum, which is a measure of interfrequency interactions between three signals. For convenient interpretation, interaction measures are most commonly normalized to be independent of constant scales of the signals such that its absolute values are bounded by one, with this limit reflecting perfect coupling. Although many different normalization factors for cross-bispectra were suggested in the literature these either do not lead to bounded measures or are themselves dependent on the coupling and not only on the scale of the signals. In this paper we suggest a normalization factor which is univariate, i.e., dependent only on the amplitude of each signal and not on the interactions between signals. Using a generalization of Hölder's inequality it is proven that the absolute value of this univariate bicoherence is bounded by zero and one. We compared three widely used normalizations to the univariate normalization concerning the significance of bicoherence values gained from resampling tests. Bicoherence values are calculated from real EEG data recorded in an eyes closed experiment from 10 subjects. The results show slightly more significant values for the univariate normalization but in general, the differences are very small or even vanishing in some subjects. Therefore, we conclude that the normalization factor does not play an important role in the bicoherence values with regard to statistical power, although a univariate normalization is the only normalization factor which fulfills all the required conditions of a proper normalization. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ethers. III. Critical use of thermodynamic parameters of activation for modeling the water penetration and drug release processes.

    PubMed

    Ferrero, Carmen; Massuelle, Danielle; Jeannerat, Damien; Doelker, Eric

    2013-09-10

    The two main purposes of this work were: (i) to critically consider the use of thermodynamic parameters of activation for elucidating the drug release mechanism from hydroxypropyl methylcellulose (HPMC) matrices, and (ii) to examine the effect of neutral (pH 6) and acidic (pH 2) media on the release mechanism. For this, caffeine was chosen as model drug and various processes were investigated for the effect of temperature and pH: caffeine diffusion in solution and HPMC gels, and drug release from and water penetration into the HPMC tablets. Generally, the kinetics of the processes was not significantly affected by pH. As for the temperature dependence, the activation energy (E(a)) values calculated from caffeine diffusivities were in the range of Fickian transport (20-40 kJ mol⁻¹). Regarding caffeine release from HPMC matrices, fitting the profiles using the Korsmeyer-Peppas model would indicate anomalous transport. However, the low apparent E(a) values obtained were not compatible with a swelling-controlled mechanism and can be assigned to the dimensional change of the system during drug release. Unexpectedly, negative apparent E(a) values were calculated for the water uptake process, which can be ascribed to the exothermic dissolution of water into the initially dry HPMC, the expansion of the matrix and the polymer dissolution. Taking these contributions into account, the true E(a) would fall into the range valid for Fickian diffusion. Consequently, a relaxation-controlled release mechanism can be dismissed. The apparent anomalous drug release from HPMC matrices results from a coupled Fickian diffusion-erosion mechanism, both at pH 6 and 2. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Plasma secretin, plasma cholecystokinin, pancreaticobiliary secretion, and fat absorption: effect of duodenal osmolality and polysorbate 80.

    PubMed

    Olsen, O; Schaffalitzky de Muckadell, O B; Cantor, P

    1987-11-01

    In 20 normal persons we investigated the effects of duodenal osmolality on the release of secretin and cholecystokinin (CCK), pancreaticobiliary secretion, and fat absorption after intestinal infusion of emulsified oleic acid (pH 6.0). The release of CCK was found to be unaffected by the changes in osmolality, whereas the plasma levels of secretin were affected in parallel with volume and bicarbonate secretion. An inverse relation was found between fatty acid absorption and release of secretin and bicarbonate secretion but not between fatty acid absorption and release of CCK. It is suggested that the secretin and CCK cells respond differently to emulsified oleic acid.

  16. Launch Lock Assemblies with Reduced Preload and Spacecraft Isolation Systems Including the Same

    NASA Technical Reports Server (NTRS)

    Barber, Tim Daniel (Inventor); Young, Ken (Inventor); Hindle, Timothy (Inventor)

    2016-01-01

    Launch lock assemblies with reduced preload are provided. The launch lock assembly comprises first and second mount pieces, a releasable clamp device, and a pair of retracting assemblies. Each retracting assembly comprises a pair of toothed members having interacting toothed surfaces. The releasable clamp device normally maintains the first and second mount pieces in clamped engagement. When the releasable clamp device is actuated, the first and second mount pieces are released from clamped engagement and one toothed member of each retracting assembly moves in an opposite direction relative to the other one toothed member of the other retracting assembly to define an axial gap on each side of the first mount piece.

  17. CPTAC Releases Cancer Proteome Confirmatory Colon Study Data | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) announces the release of the cancer proteome confirmatory colon study data. The goal of the study is to analyze the proteomes of approximately 100 confirmatory colon tumor patients, which includes tumor and adjacent normal samples, with liquid chromatography-tandem mass spectrometry (LC-MS/MS) global proteomic and phosphoproteomic profiling.

  18. FASTGRASS: A mechanistic model for the prediction of Xe, I, Cs, Te, Ba, and Sr release from nuclear fuel under normal and severe-accident conditions

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

    Rest, J.; Zawadzki, S.A.

    The primary physical/chemical models that form the basis of the FASTGRASS mechanistic computer model for calculating fission-product release from nuclear fuel are described. Calculated results are compared with test data and the major mechanisms affecting the transport of fission products during steady-state and accident conditions are identified.

  19. 77 FR 26541 - Alabama Power Company; Notice of Application for Amendment of License Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-04

    ... (cfs), beginning immediately after Commission approval until December 31, 2012. Under normal operation Alabama Power is required to release 2,000 cfs from Jordan Dam July 1 through March 31 and release a continuous base flow of 4,000 cfs for 18 hours/day and an 8,000 cfs pulse flow for 6 hours/ day from April 1...

  20. Hardness of the subchondral bone of the patella in the normal state, in chondromalacia, and in osteoarthrosis.

    PubMed

    Björkström, S; Goldie, I F

    1982-06-01

    The hardness of bone is its property of withstanding the impact of a penetrating agent. It has been found that articular degenerative changes in, for example, the tibia (knee) are combined with a decrease in the hardness of the subchondral bone. In this investigation the hardness of subchondral bone in chondromalacia and osteoarthrosis of the patella has been analysed and compared with normal subchondral bone. Using an indentation method originally described by Brinell the hardness of the subchondral bone was evaluated in 7 normal patellae, in 20 with chondromalacia and in 33 with osteoarthrosis. A microscopic and microradiographic study of the subchondral bone was carried out simultaneously. Hardness was lowest in the normal material. The mean hardness value beneath the degenerated cartilage differed only slightly from that of the normal material, but the variation of values was increased. The hardness in bone in the chondromalacia area was lower than the hardness in bone covered by surrounding normal cartilage. The mean hardness value in bone beneath normal parts of cartilage in specimens with chondromalacia was higher than the mean hardness value of the normal material. In the microscopic and microradiographic examination it became evident that there was a relationship between trabecular structure and subchondral bone hardness; high values: coarse and solid structure; low values: slender and less regular structure.

  1. New evidence for chemical fractionation of radioactive xenon precursors in fission chains

    NASA Astrophysics Data System (ADS)

    Meshik, A. P.; Pravdivtseva, O. V.; Hohenberg, C. M.

    2016-04-01

    Mass-spectrometric analyses of Xe released from acid-treated U ore reveal that apparent Xe fission yields significantly deviate from the normal values. The anomalous Xe structure is attributed to chemically fractionated fission (CFF), previously observed only in materials experienced neutron bursts. The least retentive CFF-Xe isotopes, 136Xe and 134Xe, typically escape in 2:1 proportion. Xe retained in the sample is complimentarily depleted in these isotopes. This nucleochemical process allows understanding of unexplained Xe isotopic structures in several geophysical environments, which include well gasses, ancient anorthosite, some mantle rocks, as well as terrestrial atmosphere. CFF is likely responsible for the isotopic difference in Xe in the Earth's and Martian atmospheres and it is capable of explaining the relationship between two major solar system Xe carriers: the Sun and phase-Q, found in meteorites.

  2. Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium

    PubMed Central

    Rodriguez-Sinovas, Antonio; García-Dorado, David; Ruiz-Meana, Marisol; Soler-Soler, Jordi

    2004-01-01

    Transient inhibition of gap junction (GJ)-mediated communication with heptanol during myocardial reperfusion limits infarct size. However, inhibition of cell coupling in normal myocardium may be arrhythmogenic. The purpose of this study was to test the hypothesis that the consequences of GJ inhibition may be magnified in reperfused myocardium compared with normal tissue, thus allowing the inhibition of GJs in reperfused tissue while only minimally modifying overall macroscopic cell coupling in normal myocardium. Concentration–response curves were defined for the effects of heptanol, 18α-glycyrrhetinic acid, halothane, and palmitoleic acid on conduction velocity, tissue electrical impedance, developed tension and lactate dehydrogenase (LDH) release in normoxically perfused rat hearts (n = 17). Concentrations lacking significant effects on tissue impedance were added during the initial 15 min of reperfusion in hearts submitted to 60 min (n = 43) or 30 min (n = 35) of ischaemia. These concentrations markedly increased myocardial electrical impedance (resistivity and phase angle) in myocardium reperfused after either 30 or 60 min of ischaemia, and reduced reperfusion-induced LDH release after 1 h of ischaemia by 83.6, 57.9, 51.7 and 52.5% for heptanol, 18α-glycyrrhetinic acid, halothane and palmitoleic acid, respectively. LDH release was minimal in hearts submitted to 30 min of ischaemia, independently of group allocation. In conclusion, the present results strongly support the hypothesis that intercellular communication in postischaemic myocardium may be effectively reduced by concentrations of GJ inhibitors affecting only minimally overall electrical impedance in normal myocardium. Reduction of cell coupling during initial reperfusion was consistently associated with attenuated lethal reperfusion injury. PMID:15218064

  3. Lactose digestion by human jejunal biopsies: the relationship between hydrolysis and absorption.

    PubMed Central

    Dawson, D J; Lobley, R W; Burrows, P C; Miller, V; Holmes, R

    1986-01-01

    The relationship between lactose hydrolysis and absorption of released glucose was investigated by determining the kinetics of lactose digestion by jejunal biopsies incubated in vitro. Lactase activity in intact biopsies correlated with conventional assay of tissue homogenates (r = 0.85, p less than 0.001), and glucose uptake from 28 mM lactose was directly proportional to lactase activity (r = 0.95, p less than 0.001) in 21 subjects with normal lactase levels, six with hypolactasia (primary or secondary to coeliac disease) and two with lactose intolerance but normal lactase activity. Kinetic analysis at 0.56-56 mM lactose in five normal subjects showed saturable kinetics for hydrolysis (app Km = 33.9 +/- 2.2 mM; app Vmax = 26.5 +/- 1.1 nmol/min/mg dry weight) but glucose uptake could be fitted to a model either of saturable uptake (app Kt = 47.2 +/- 0.3 mM; app Jmax = 14.1 +/- 0.2 nmol/min/mg) or saturable uptake plus a linear component (app Kt = 21.3 +/- 1.15; app Jmax = 4.59 +/- 0.12; app Kd = 0.093 +/- 0.010 nmol/min/mg/mM). The proportion of glucose taken into the tissue did not significantly exceed 50% of the total released at any lactose concentration suggesting the lack of an efficient capture mechanism for the released glucose. The results suggest that lactose hydrolysis is the rate limiting step in the overall absorption of glucose from lactose in vitro, and that the relationship between hydrolysis and absorption is the same in normal subjects and in hypolactasic subjects. PMID:3084346

  4. Nanopore thin film enabled optical platform for drug loading and release.

    PubMed

    Song, Chao; Che, Xiangchen; Que, Long

    2017-08-07

    In this paper, a drug loading and release device fabricated using nanopore thin film and layer-by-layer (LbL) nanoassembly is reported. The nanopore thin film is a layer of anodic aluminum oxide (AAO), consisting of honeycomb-shape nanopores. Using the LbL nanoassembly process, the drug, using gentamicin sulfate (GS) as the model, can be loaded into the nanopores and the stacked layers on the nanopore thin film surface. The drug release from the device is achieved by immersing it into flowing DI water. Both the loading and release processes can be monitored optically. The effect of the nanopore size/volume on drug loading and release has also been evaluated. Further, the neuron cells have been cultured and can grow normally on the nanopore thin film, verifying its bio-compatibility. The successful fabrication of nanopore thin film device on silicon membrane render it as a potential implantable controlled drug release device.

  5. The effect of capsaicin application on mast cells in normal human skin.

    PubMed

    Bunker, C B; Cerio, R; Bull, H A; Evans, J; Dowd, P M; Foreman, J C

    1991-05-01

    Peptides released from sensory nerves during an axon reflex are thought to cause mast cell degranulation, histamine (Hi) release and Hi-induced vasodilatation leading to the flare of the triple response. Capsaicin stimulates peptide release from sensory neurones and causes flare in vivo but does not cause Hi release from mast cells in vitro. The effects of capsaicin on mast cell degranulation in human skin in vivo has been studied by histological examination of skin biopsies after topical capsicin (1%) treatment of stratum corneum-denuded forearm in four volunteers. The results show a significant reduction in the visible numbers of mast cells and the appearance of degranulated mast cells ghosts in the skin six hours after capsaicin application. Since capsaicin itself does not release Hi from mast cells, these data suggest that capsaicin-induced release of peptides from neurones could cause mast cell degranulation.

  6. Correlation of individual differences in schizotypal personality traits with amphetamine-induced dopamine release in striatal and extrastriatal brain regions.

    PubMed

    Woodward, Neil D; Cowan, Ronald L; Park, Sohee; Ansari, M Sib; Baldwin, Ronald M; Li, Rui; Doop, Mikisha; Kessler, Robert M; Zald, David H

    2011-04-01

    Schizotypal personality traits are associated with schizophrenia spectrum disorders, and individuals with schizophrenia spectrum disorders demonstrate increased dopamine transmission in the striatum. The authors sought to determine whether individual differences in normal variation in schizotypal traits are correlated with dopamine transmission in the striatum and in extrastriatal brain regions. Sixty-three healthy volunteers with no history of psychiatric illness completed the Schizotypal Personality Questionnaire and underwent positron emission tomography imaging with [(18)F]fallypride at baseline and after administration of oral d-amphetamine (0.43 mg/kg). Dopamine release, quantified by subtracting each participant's d-amphetamine scan from his or her baseline scan, was correlated with Schizotypal Personality Questionnaire total and factor scores using region-of-interest and voxel-wise analyses. Dopamine release in the striatum was positively correlated with overall schizotypal traits. The association was especially robust in the associative subdivision of the striatum. Voxel-wise analyses identified additional correlations between dopamine release and schizotypal traits in the left middle frontal gyrus and left supramarginal gyrus. Exploratory analyses of Schizotypal Personality Questionnaire factor scores revealed correlations between dopamine release and disorganized schizotypal traits in the striatum, thalamus, medial prefrontal cortex, temporal lobe, insula, and inferior frontal cortex. The association between dopamine signaling and psychosis phenotypes extends to individual differences in normal variation in schizotypal traits and involves dopamine transmission in both striatal and extrastriatal brain regions. Amphetamine-induced dopamine release may be a useful endophenotype for investigating the genetic basis of schizophrenia spectrum disorders.

  7. Self-assembling N-(9-Fluorenylmethoxycarbonyl)-l-Phenylalanine hydrogel as novel drug carrier.

    PubMed

    Snigdha, Kirti; Singh, Brijesh K; Mehta, Abijeet Singh; Tewari, R P; Dutta, P K

    2016-12-01

    Supramolecular hydrogel as a novel drug carrier was prepared from N-(9-Fluorenylmethoxycarbonyl) (Fmoc) modified l-phenylalanine. Its different properties like stability at different pH, temperature and rheology were evaluated in reference to salicylic acid (SA) as a model drug, entrapped in the supramolecular hydrogel network. The release behaviour of SA drug in supramolecular hydrogel was investigated by UV-vis spectroscopy. The influence of hydrogelator, pH values of the accepting media, temperature and concentration of SA drug on the release behaviour was investigated under static conditions. The results indicated that the release rate of SA in the supramolecular hydrogels was slightly retarded with an increase of the hydrogelator concentration. Also, the release rates of SA increased with an increase of temperature and its concentration. Furthermore, the release behaviour of SA was found to be different at various pH values in buffers. The study of the release kinetics indicated that the release behaviour of SA from the carrier was in accord with the Peppas model and the diffusion controlled mechanism involved in the Fickian model. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Superresolution Modeling of Calcium Release in the Heart

    PubMed Central

    Walker, Mark A.; Williams, George S.B.; Kohl, Tobias; Lehnart, Stephan E.; Jafri, M. Saleet; Greenstein, Joseph L.; Lederer, W.J.; Winslow, Raimond L.

    2014-01-01

    Stable calcium-induced calcium release (CICR) is critical for maintaining normal cellular contraction during cardiac excitation-contraction coupling. The fundamental element of CICR in the heart is the calcium (Ca2+) spark, which arises from a cluster of ryanodine receptors (RyR). Opening of these RyR clusters is triggered to produce a local, regenerative release of Ca2+ from the sarcoplasmic reticulum (SR). The Ca2+ leak out of the SR is an important process for cellular Ca2+ management, and it is critically influenced by spark fidelity, i.e., the probability that a spontaneous RyR opening triggers a Ca2+ spark. Here, we present a detailed, three-dimensional model of a cardiac Ca2+ release unit that incorporates diffusion, intracellular buffering systems, and stochastically gated ion channels. The model exhibits realistic Ca2+ sparks and robust Ca2+ spark termination across a wide range of geometries and conditions. Furthermore, the model captures the details of Ca2+ spark and nonspark-based SR Ca2+ leak, and it produces normal excitation-contraction coupling gain. We show that SR luminal Ca2+-dependent regulation of the RyR is not critical for spark termination, but it can explain the exponential rise in the SR Ca2+ leak-load relationship demonstrated in previous experimental work. Perturbations to subspace dimensions, which have been observed in experimental models of disease, strongly alter Ca2+ spark dynamics. In addition, we find that the structure of RyR clusters also influences Ca2+ release properties due to variations in inter-RyR coupling via local subspace Ca2+ concentration ([Ca2+]ss). These results are illustrated for RyR clusters based on super-resolution stimulated emission depletion microscopy. Finally, we present a believed-novel approach by which the spark fidelity of a RyR cluster can be predicted from structural information of the cluster using the maximum eigenvalue of its adjacency matrix. These results provide critical insights into CICR dynamics in heart, under normal and pathological conditions. PMID:25517166

  9. Assessment of menstrual blood loss in Belgian users of a new T-shaped levonorgestrel-releasing intrauterine system.

    PubMed

    Wildemeersch, Dirk; Rowe, Patrick J

    2005-06-01

    This study was conducted to evaluate the effect of a T-shaped levonorgestrel-releasing intrauterine system (Femilis, LNG IUS) on the amount of menstrual blood loss (MBL) in women with and without menorrhagia. The daily release of the LNG IUS was approximately 20 mug. In 60 Belgian women, less than 48 years of age at study enrollment, using the Femilis LNG IUS for 4 to more than 30 months, MBL was assessed with the visual assessment technique. Twenty-eight women had normal menstrual periods at baseline (menstrual score <185) and 32 women had idiopathic menorrhagia (menstrual score > or =185). Menstrual blood loss scores dropped significantly during the observation period in all women except one. The median menstrual score at baseline in women with normal menstrual bleeding was 140 (range 80-160) and dropped to a median score of 5 (range 0-150) at follow-up, a decrease of 96%. In the 32 women with menorrhagic bleeding at baseline, menstrual flow dropped from a median score of 232 (range 185-450) at baseline to a median score of 3 (range 0-50) at follow-up, a decrease of 99%. Twenty women developed amenorrhea (33%): 10 in the group of women with normal menstruation and 10 in those women with menorrhagia. Most of the remaining women had oligomenorrhea requiring the use of a few panty-liners only. In one woman, MBL did not decrease, thus requiring further evaluation. The impact on MBL of this new 20 mug/day LNG-releasing IUS confirms other studies with devices releasing the same or lower amounts of LNG. The strong endometrial suppression is the principal mechanism explaining the effect on MBL. The strong effect on MBL of this contraceptive method offers an important health benefit and improvement in quality of life, particularly in women with heavy bleeding and anemia, as other treatment modalities are less effective, more costly, more invasive or not readily available.

  10. Integrated Quantitative Transcriptome Maps of Human Trisomy 21 Tissues and Cells

    PubMed Central

    Pelleri, Maria Chiara; Cattani, Chiara; Vitale, Lorenza; Antonaros, Francesca; Strippoli, Pierluigi; Locatelli, Chiara; Cocchi, Guido; Piovesan, Allison; Caracausi, Maria

    2018-01-01

    Down syndrome (DS) is due to the presence of an extra full or partial chromosome 21 (Hsa21). The identification of genes contributing to DS pathogenesis could be the key to any rational therapy of the associated intellectual disability. We aim at generating quantitative transcriptome maps in DS integrating all gene expression profile datasets available for any cell type or tissue, to obtain a complete model of the transcriptome in terms of both expression values for each gene and segmental trend of gene expression along each chromosome. We used the TRAM (Transcriptome Mapper) software for this meta-analysis, comparing transcript expression levels and profiles between DS and normal brain, lymphoblastoid cell lines, blood cells, fibroblasts, thymus and induced pluripotent stem cells, respectively. TRAM combined, normalized, and integrated datasets from different sources and across diverse experimental platforms. The main output was a linear expression value that may be used as a reference for each of up to 37,181 mapped transcripts analyzed, related to both known genes and expression sequence tag (EST) clusters. An independent example in vitro validation of fibroblast transcriptome map data was performed through “Real-Time” reverse transcription polymerase chain reaction showing an excellent correlation coefficient (r = 0.93, p < 0.0001) with data obtained in silico. The availability of linear expression values for each gene allowed the testing of the gene dosage hypothesis of the expected 3:2 DS/normal ratio for Hsa21 as well as other human genes in DS, in addition to listing genes differentially expressed with statistical significance. Although a fraction of Hsa21 genes escapes dosage effects, Hsa21 genes are selectively over-expressed in DS samples compared to genes from other chromosomes, reflecting a decisive role in the pathogenesis of the syndrome. Finally, the analysis of chromosomal segments reveals a high prevalence of Hsa21 over-expressed segments over the other genomic regions, suggesting, in particular, a specific region on Hsa21 that appears to be frequently over-expressed (21q22). Our complete datasets are released as a new framework to investigate transcription in DS for individual genes as well as chromosomal segments in different cell types and tissues. PMID:29740474

  11. 19 CFR 351.405 - Calculation of normal value based on constructed value.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... value. 351.405 Section 351.405 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE... constructed value as the basis for normal value where: neither the home market nor a third country market is... a fictitious market are disregarded; no contemporaneous sales of comparable merchandise are...

  12. Application of a system for measuring foot plantar pressure for evaluation of human mobility

    NASA Astrophysics Data System (ADS)

    Klimiec, Ewa; Jasiewicz, Barbara; Zaraska, Krzysztof; Piekarski, Jacek; Guzdek, Piotr; Kołaszczyński, Grzegorz

    2016-11-01

    The paper presents evaluation of human mobility by gait analysis, carried out in natural conditions (outside laboratory). Foot plantar pressure is measured using a shoe insole with 8 sensors placed in different anatomical zones of the foot, and placed inside a sports footwear. Polarized PVDF foil is used as a sensor material. A wireless transmission system is used to transmit voltage values to the computer. Due to linear relationship between force and transducer voltage, energy released during walking in arbitrary units can be calculated as integral of the square of transducer voltage over time. Gait measurements have been done over the next few days on healthy person during normal walking and slow walking. Performed measurements allow determination of walking speed (number of steps per second), gait rhythm and manner of walking (applying force to inside versus outside part of the sole). It is found that switching from normal to slow walk increases gait energy by 25% while the pressure distribution across the anatomical regions of the foot remains unchanged. The results will be used for developing a programme for evaluation of patients with cardiac failure and future integration of actimetry with pulse and spirometry measurements.

  13. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism

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

    Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

    To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarlymore » decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism.« less

  14. A novel fibrinogen variant--Liberec: dysfibrinogenaemia associated with gamma Tyr262Cys substitution.

    PubMed

    Kotlín, Roman; Sobotková, Alzbeta; Suttnar, Jirí; Salaj, Peter; Walterová, Lenka; Riedel, Tomás; Reicheltová, Zuzana; Dyr, Jan Evangelista

    2008-08-01

    A 22-yr-old woman had abnormal preoperative coagulation test results and congenital dysfibrinogenaemia was suspected. The patient from Liberec (Czech Republic) had a low fibrinogen plasma level as determined by Clauss method, normal fibrinogen level as determined by immunoturbidimetrical method, and prolonged thrombin time. To identify the genetic mutation responsible for this dysfibrinogen, genomic DNA extracted from the blood was analysed. Fibrin polymerisation measurement, kinetics of fibrinopeptide release, fibrinogen clottability measurement and scanning electron microscopy were performed. DNA sequencing showed the heterozygous fibrinogen gamma Y262C mutation. Kinetics of fibrinopeptide release was normal, however fibrin polymerisation was impaired. Fibrinogen clottability measurement showed that only about 45% molecules of fibrinogen are involved in the clot formation. Scanning electron microscopy revealed thicker fibres, which were significantly different from the normal control. A case of dysfibrinogenaemia, found by routine coagulation testing, was genetically identified as a novel fibrinogen variant (gamma Y262C) that has been named Liberec.

  15. Markers of inflammation in alveolar cells exposed to fine particulate matter from prescribed fires and urban air.

    PubMed

    Myatt, Theodore A; Vincent, Michael S; Kobzik, Lester; Naeher, Luke P; MacIntosh, David L; Suh, Helen

    2011-10-01

    To assess the effect of fine particulate matter (PM(2.5)) from different particle sources on tumor necrosis factor- (TNF-) α, we measured TNF production from rat alveolar macrophages (AM) and human dendritic cells (DC) exposed to PM(2.5) from different sources. Fire-related PM(2.5) samples, rural ambient, and urban indoor and outdoor samples were collected in the Southeast United States. Tumor necrosis factor release was measured from rat AM and human DC following incubation with PM(2.5). Tumor necrosis factor release in AMs was greatest for fire-related PM(2.5) compared with other samples (TNF: P value = 0.005; mortality: P value = 0.005). Tumor necrosis factor releases from the DCs and AMs exposed to fire-associated PM(2.5) were strongly correlated (r = 0.87, P value < 0.0001). Particulate matter exposure produces TNF release consistent with pulmonary inflammation in rat AMs and human DCs, with the response in rat AMs differing by particle source.

  16. Effect of sodium tripolyphosphate concentration and simulated gastrointestinal fluids on release profile of paracetamol from chitosan microsphere

    NASA Astrophysics Data System (ADS)

    Mulia, Kamarza; Andrie; Krisanti, Elsa A.

    2018-03-01

    The problem to overcome in oral drug administration is the significant pH changes present in the human digestive system. In this study, ionotropic gelation method employing 2-8% (w/v) tripolyphosphate solutions were used to crosslink chitosan microspheres for a controlled release of paracetamol as a model drug. The release profiles of paracetamol from chitosan microspheres were determined using simulated gastrointestinal fluids having pH values of 1.2, 6.8, and 7.4. The results showed that the paracetamol loading and the encapsulation efficiency values increased with increasing concentration of tripolyphosphate solutions used in the preparation step. Paracetamol released at pH 1.2 and 6.8 buffer solutions was significantly higher than that at pH 7.4; also, more paracetamol was released in the presence of α-amylase and β-glucosidase enzymes. The release profiles showed zero-order release behaviour up to 8 hours where the highest drug release was 39% of the paracetamol loaded in the chitosan microspheres, indicating a strong crosslinking between chitosan and TPP anions. The relatively low accumulated drug release could be compensated by employing suitable enzymes, lower TPP solution concentration, and addition of other biodegradable polymer to reduce the TPP crosslink.

  17. Formulation effects on the mechanical and release properties of metronidazole suppositories.

    PubMed

    Adegboye, T A; Itiola, O A

    2003-09-01

    A study of the effects of Tween 20 and Tween 80 non-ionic surfactants, and witepsol H15 and polyethylene glycol (PEG) 2850 bases, on the mechanical and release properties of metronidazole suppositories was made. Mechanical strength was assessed by breaking strength values F. The values of F increased with increase in concentration of surfactant. The values of F for formulations containing Tween 20 were higher than those obtained for formulations containing Tween 80. Witepsol bases gave higher values of F than corresponding PEG bases. Release characteristics were assessed by the time for 80% drug release (t80), values of dissolution rate constants, k1 and k2 and the time of intersection, t1. The values of t80 decreased while those of k1 and k2 increased with increase in surfactant concentration. The values of t80 were lower, while those of k1 and k2 were higher, for formulations containing Tween 20 than for those formulations containing Tween 80. Witepsol bases gave lower t80 values and higher k1 and k2 values than their corresponding PEG bases. The concentration of surfactant, C, had the largest individual effect on the mechanical and release parameters while the nature of surfactant, S, had the lowest. The ranking for the individual effects of the variables on F and k1 was C > N > S, on t80 and k2 was C > N approximately = S, was on t1 was C = N = S. The interactions between S and C were largest for F, t80 and k2, and lowest for k1 and t1. The ranking of the interaction effects of the variables on F and k2 was S-C > N-C > N-S, on t80 was S-C > N-S approximately = N-C, on k1 was N-C > N-S > S-C, and on t1 was N-S = N-C > S-C. The results suggest that the individual and interaction effects of formulation variables would provide useful guides in optimizing metronidazole suppository formulations.

  18. Nitrous-acid-mediated synthesis of iron-nitrosyl-porphyrin: pH-dependent release of nitric oxide.

    PubMed

    Bhuyan, Jagannath; Sarkar, Sabyasachi

    2012-11-01

    Two iron-nitrosyl-porphyrins, nitrosyl[meso-tetrakis(3,4,5-trimethoxyphenylporphyrin]iron(II) acetic acid solvate (3) and nitrosyl[meso-tetrakis(4-methoxyphenylporphyrin]iron(II) CH(2)Cl(2) solvate (4), were synthesized in quantitative yield by using a modified procedure with nitrous acid, followed by oxygen-atom abstraction by triphenylphosphine under an argon atmosphere. These nitrosyl porphyrins are in the {FeNO}(7) class. Under an argon atmosphere, these compounds are relatively stable over a broad range of pH values (4-8) but, under aerobic conditions, they release nitric oxide faster at high pH values than that at low pH values. The generated nitric-oxide-free iron(III)-porphyrin can be re-nitrosylated by using nitrous acid and triphenylphosphine. The rapid release of NO from these Fe(II) complexes at high pH values seems to be similar to that in nitrophorin, a nitric-oxide-transport protein, which formally possesses Fe(III). However, because the release of NO occurs from ferrous-nitrosyl-porphyrin under aerobic conditions, these compounds are more closely related to nitrobindin, a recently discovered heme protein. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. 77 FR 47918 - Information Collection Activities (Released Rates)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... decision in Released Rates of Motor Common Carriers of Household Goods, Docket No. RR 999 (Amendment No. 5... loss or damage that occurs during interstate household-good moves. See Safe, Accountable, Flexible... elects anything other than full-value protection. See Released Rates of Motor Common Carriers of...

  20. Heat release effects in a turbulent, reacting shear layer

    NASA Astrophysics Data System (ADS)

    Hermanson, James Carl

    The effects of heat release were studied in a planar, gaseous reacting mixing layer formed between free streams containing hydrogen and fluorine in inert diluents. Sufficiently high concentrations of reactants were employed to produce adiabatic flame temperature rises of up to 940 K (1240 K absolute). The Reynolds number at the measuring station, based on velocity difference, 1% temperature thickness and cold kinematic viscosity was approximately 6x10^4. The temperature field was measured with cold wire resistance thermometers and thermocouples. Flow visualization was accomplished by schlieren spark and motion picture photography. Mean velocity information was extracted from mean pitot probe dynamic pressure measurements.Though the displacement thickness of the layer, for zero streamwise pressure gradient, increased with increasing heat release, the actual growth rate of the layer did not increase, but instead decreased slightly. The overall entrainment into the layer was seen to be substantially reduced as a consequence of heat release. Calculations showed that the decrease in layer growth rate can be accounted for by a corresponding reduction in turbulent shear stress.The mean temperature rise profiles, normalized by the adiabatic flame temperature rise, were not greatly changed in shape by heat release. A small decrease in normalized mean temperature rise with heat release was observed. Large scale coherent structures were observed to persist at all levels of heat release in this investigation. The mean structure spacing decreased with increasing temperature. This decrease exceeded the rate of layer growth rate reduction, and suggests that the mechanisms of vortex amalgamation were, to some extent, inhibited by heat release.Imposition of a favorable pressure gradient resulted in additional thinning of the layer, and caused a slight increase in the mixing and amount of chemical product formation. The change in layer growth rate can be shown to be related to a change in free stream velocity ratio induced by pressure gradient.

  1. Model of reticuloendothelial iron metabolism in humans: Abnormal behavior in idiopathic hemochromatosis and in inflammation

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

    Fillet, G.; Beguin, Y.; Baldelli, L.

    1989-08-01

    Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated frommore » the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin (P less than .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P less than .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores.« less

  2. Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

    PubMed Central

    Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

    2013-01-01

    Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

  3. 49 CFR 229.77 - Current collectors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Electrical System § 229... engineer's normal position in the cab. Pantographs that automatically rise when released shall have an...

  4. 49 CFR 229.77 - Current collectors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Electrical System § 229... engineer's normal position in the cab. Pantographs that automatically rise when released shall have an...

  5. 49 CFR 229.77 - Current collectors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Electrical System § 229... engineer's normal position in the cab. Pantographs that automatically rise when released shall have an...

  6. 49 CFR 229.77 - Current collectors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Electrical System § 229... engineer's normal position in the cab. Pantographs that automatically rise when released shall have an...

  7. 49 CFR 229.77 - Current collectors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Electrical System § 229... engineer's normal position in the cab. Pantographs that automatically rise when released shall have an...

  8. Are normal decision-makers sensitive to changes in value contrast under uncertainty? Evidence from the Iowa Gambling Task.

    PubMed

    Lee, We-Kang; Su, Yi-An; Song, Tzu-Jiun; Chiu, Yao-Chu; Lin, Ching-Hung

    2014-01-01

    The Iowa Gambling Task (IGT) developed by Bechara et al. in 1994 is used to diagnose patients with Ventromedial Medial Prefrontal Cortex (VMPFC) lesions, and it has become a landmark in research on decision making. According to Bechara et al., the manipulation of progressive increments of monetary value can normalize the performance of patients with VMPFC lesions; thus, they developed a computerized version of the IGT. However, the empirical results showed that patients' performances did not improve as a result of this manipulation, which suggested that patients with VMPFC lesions performed myopically for future consequences. Using the original version of the IGT, some IGT studies have demonstrated that increments of monetary value significantly influence the performance of normal subjects in the IGT. However, other research has resulted in inconsistent findings. In this study, we used the computerized IGT (1X-IGT) and manipulated the value contrast of progressive increments (i.e., by designing the 10X-IGT, which contained 10 times of progressive increment) to investigate the influence of value contrast on the performance of normal subjects. The resulting empirical observations indicated that the value contrast (1X- vs. 10X-IGT) of the progressive increment had no effect on the performance of normal subjects. This study also provides a discussion of the issue of value in IGT-related studies. Moreover, we found the "prominent deck B phenomenon" in both versions of the IGT, which indicated that the normal subjects were guided mostly by the gain-loss frequency, rather than by the monetary value contrast. In sum, the behavioral performance of normal subjects demonstrated a low correlation with changes in monetary value, even in the 10X-IGT.

  9. Recommended Parameter Values for GENII Modeling of Radionuclides in Routine Air and Water Releases

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

    Snyder, Sandra F.; Arimescu, Carmen; Napier, Bruce A.

    The GENII v2 code is used to estimate dose to individuals or populations from the release of radioactive materials into air or water. Numerous parameter values are required for input into this code. User-defined parameters cover the spectrum from chemical data, meteorological data, agricultural data, and behavioral data. This document is a summary of parameter values that reflect conditions in the United States. Reasonable regional and age-dependent data is summarized. Data availability and quality varies. The set of parameters described address scenarios for chronic air emissions or chronic releases to public waterways. Considerations for the special tritium and carbon-14 modelsmore » are briefly addressed. GENIIv2.10.0 is the current software version that this document supports.« less

  10. Economic valuation of environmental benefits of removing pharmaceutical and personal care products from WWTP effluents by ozonation.

    PubMed

    Molinos-Senante, M; Reif, R; Garrido-Baserba, M; Hernández-Sancho, F; Omil, F; Poch, M; Sala-Garrido, R

    2013-09-01

    Continuous release of pharmaceutical and personal care products (PPCPs) present in effluents from wastewater treatment plants (WWTPs) is nowadays leading to the adoption of specific measures within the framework of the Directive 2000/60/EC (Water Framework Directive). The ozonation process, normally employed for drinking water production, has also proven its potential to eliminate PPCPs from secondary effluents in spite of their low concentrations. However, there is a significant drawback related with the costs associated with its implementation. This lack of studies is especially pronounced regarding the economic valuation of the environmental benefits associated to avoid the discharge of these pollutants into water bodies. For the first time the shadow prices of 5 PPCPs which are ethynilestradiol, sulfamethoxazole, diclofenac, tonalide and galaxolide from treated effluent using a pilot-scale ozonation reactor have been estimated. From non-sensitive areas their values are -73.73; -34.95; -42.20; -10.98; and -8.67 respectively and expressed in €/kg. They represent a proxy to the economic value of the environmental benefits arisen from undischarged pollutants. This paper contributes to value the environmental benefits of implementing post-treatment processes aimed to achieve the quality standards required by the Priority Substances Directive. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. The mutagenicity of cassava (Manihot esculenta Crantz) preparations.

    PubMed

    De Meester, C; Rollmann, B; Mupenda, K; Mary, Y

    1990-01-01

    Different cassava products were found to contain mutagenic activities in the Ames test. This paper describes how the flavonol quercetin is released during the cooking of fresh cassava leaves, following a process very similar to culinary habits. The hydrolysis of the glucoside(s) and the release of free quercetin has been followed by the monitoring of mutagenic activities with a simultaneous isolation and purification by thin-layer chromatography. The fluorodensitometric method applied revealed that fresh leaves contained about 1300 mg quercetin per kg wet weight, of which 800 mg were released during a normal cooking process.

  12. Percutaneous release of the plantar fascia. New surgical procedure

    PubMed Central

    Oliva, Francesco; Piccirilli, Eleonora; Tarantino, Umberto; Maffulli, Nicola

    2017-01-01

    Summary Background Plantar fasciopathy presents with pain at the plantar and medial aspect of the heel. If chronic, it can negatively impact on quality of life. Plantar fasciopathy is not always self-limiting, and can be debilitating. Methods Surgical management involves different procedures. We describe a percutaneous plantar fascia release. A minimally invasive access to the plantar tuberosity of the calcaneus is performed, and a small scalpel blade is used to release the fascia. Conclusion With this procedure, skin healing problems, nerve injuries, infection and prolonged recovery time are minimised, allowing early return to normal activities. Level of Evidence V. PMID:29264346

  13. Functional Consequence of Distal Brachioradialis Tendon Release: A Biomechanical Study

    PubMed Central

    Tirrell, Timothy F.; Franko, Orrin I.; Bhola, Siddharth; Hentzen, Eric R.; Abrams, Reid A.; Lieber, Richard L.

    2013-01-01

    Purpose Open reduction and internal fixation of distal radius fractures often necessitates release of the brachioradialis from the radial styloid. However, this common procedure has the potential to decrease elbow flexion strength. To determine the potential morbidity associated with brachioradialis release, we measured the change in elbow torque as a function of incremental release of the brachioradialis insertion footprint. Methods In 5 upper extremity cadaveric specimens, the brachioradialis tendon was systematically released from the radius, and the resultant effect on brachioradialis elbow flexion torque was measured. Release distance was defined as the distance between the release point and the tip of the radial styloid. Results Brachioradialis elbow flexion torque dropped to 95%, 90% and 86% of its original value at release distances of 27mm, 46mm, and 52mm, respectively. Importantly, brachioradialis torque remained above 80% of its original value at release distances up to 7 centimeters. Conclusions Our data demonstrate that release of the brachioradialis tendon from its insertion has minor effects on its ability to transmit force to the distal radius. Clinical Relevance These data may imply that release of the distal brachioradialis tendon during distal radius open reduction internal fixation can be performed without meaningful functional consequences to elbow flexion torque. Even at large release distances, overall elbow flexion torque loss after brachioradialis release would be expected to be less than 5% due to the much larger contributions of the biceps and brachialis. Use of the brachioradialis as a tendon transfer donor should not be limited by concerns of elbow flexion loss, and the tendon could be considered as an autograft donor. PMID:23528425

  14. Speech-on-speech masking with variable access to the linguistic content of the masker speech for native and nonnative english speakers.

    PubMed

    Calandruccio, Lauren; Bradlow, Ann R; Dhar, Sumitrajit

    2014-04-01

    Masking release for an English sentence-recognition task in the presence of foreign-accented English speech compared with native-accented English speech was reported in Calandruccio et al (2010a). The masking release appeared to increase as the masker intelligibility decreased. However, it could not be ruled out that spectral differences between the speech maskers were influencing the significant differences observed. The purpose of the current experiment was to minimize spectral differences between speech maskers to determine how various amounts of linguistic information within competing speech Affiliationect masking release. A mixed-model design with within-subject (four two-talker speech maskers) and between-subject (listener group) factors was conducted. Speech maskers included native-accented English speech and high-intelligibility, moderate-intelligibility, and low-intelligibility Mandarin-accented English. Normalizing the long-term average speech spectra of the maskers to each other minimized spectral differences between the masker conditions. Three listener groups were tested, including monolingual English speakers with normal hearing, nonnative English speakers with normal hearing, and monolingual English speakers with hearing loss. The nonnative English speakers were from various native language backgrounds, not including Mandarin (or any other Chinese dialect). Listeners with hearing loss had symmetric mild sloping to moderate sensorineural hearing loss. Listeners were asked to repeat back sentences that were presented in the presence of four different two-talker speech maskers. Responses were scored based on the key words within the sentences (100 key words per masker condition). A mixed-model regression analysis was used to analyze the difference in performance scores between the masker conditions and listener groups. Monolingual English speakers with normal hearing benefited when the competing speech signal was foreign accented compared with native accented, allowing for improved speech recognition. Various levels of intelligibility across the foreign-accented speech maskers did not influence results. Neither the nonnative English-speaking listeners with normal hearing nor the monolingual English speakers with hearing loss benefited from masking release when the masker was changed from native-accented to foreign-accented English. Slight modifications between the target and the masker speech allowed monolingual English speakers with normal hearing to improve their recognition of native-accented English, even when the competing speech was highly intelligible. Further research is needed to determine which modifications within the competing speech signal caused the Mandarin-accented English to be less effective with respect to masking. Determining the influences within the competing speech that make it less effective as a masker or determining why monolingual normal-hearing listeners can take advantage of these differences could help improve speech recognition for those with hearing loss in the future. American Academy of Audiology.

  15. Evaluation of Gum of Moringa oleifera as a Binder and Release Retardant in Tablet Formulation

    PubMed Central

    Panda, D. S.; Choudhury, N. S. K.; Yedukondalu, M.; Si, S.; Gupta, R.

    2008-01-01

    The present study was undertaken to find out the potential of gum from Moringa oleifera to act as a binder and release retardant in tablet formulations. The effect of calcium sulphate dihydrate (water insoluble) and lactose (water soluble) diluent on the release of propranolol hydrochloride was studied. The DSC thermograms of drug, gum and mixture of gum/drug indicated no chemical interaction. Tablets (F1, F2, F3, and F4) were prepared containing calcium sulphate dihydrate as diluent, propranolol hydrochloride as model drug using 10%, 8%, 6% and 4% w/v of gum solution as binder. Magnesium stearate was used as lubricant. Physical and technological properties of granules and tablets like flow rate, Carr index, Hausner ratio, angle of repose, hardness, friability and disintegration time were determined and found to be satisfactory. Tablets were prepared by wet granulation method containing calcium sulphate dihydrate as excipient, propranolol hydrochloride as model drug using 10%, 20% and 30% of gum as release retardant, magnesium stearate was used as lubricant. Similarly tablets were prepared replacing lactose with calcium sulphate dihydrate. Despite of the widely varying physico-chemical characteristics of the excipients, the drug release profiles were found to be similar. The drug release increased with increasing proportions of the excipient and decreased proportion of the gum irrespective of the solubility characteristics of the excipient. The values of release exponent ‘n’ are between 0.37 and 0.54. This implies that the release mechanism is Fickian. There is no evidence that the dissolution or erosion of the excipient has got any effect on the release of the drug. The t50% values for tablets containing calcium sulphate dihydrate were on an average 10%-15% longer than the tablets containing lactose as excipient. These relatively small differences in t50% values suggest that the nature of excipient used appeared to play a minor role in regulating the release, while the gum content was a major factor. PMID:21394258

  16. Impact of Corrections to the Spallings Volume Calculation on Waste Isolation Pilot Plant Performance Assessment

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

    Kicker, Dwayne Curtis; Herrick, Courtney G; Zeitler, Todd

    2015-11-01

    The numerical code DRSPALL (from direct release spallings) is written to calculate the volume of Waste Isolation Pilot Plant solid waste subject to material failure and transport to the surface (i.e., spallings) as a result of a hypothetical future inadvertent drilling intrusion into the repository. An error in the implementation of the DRSPALL finite difference equations was discovered and documented in a software problem report in accordance with the quality assurance procedure for software requirements. This paper describes the corrections to DRSPALL and documents the impact of the new spallings data from the modified DRSPALL on previous performance assessment calculations.more » Updated performance assessments result in more simulations with spallings, which generally translates to an increase in spallings releases to the accessible environment. Total normalized radionuclide releases using the modified DRSPALL data were determined by forming the summation of releases across each potential release pathway, namely borehole cuttings and cavings releases, spallings releases, direct brine releases, and transport releases. Because spallings releases are not a major contributor to the total releases, the updated performance assessment calculations of overall mean complementary cumulative distribution functions for total releases are virtually unchanged. Therefore, the corrections to the spallings volume calculation did not impact Waste Isolation Pilot Plant performance assessment calculation results.« less

  17. Effects of cryopreservation on chimeric antigen receptor T cell functions.

    PubMed

    Xu, Hao; Cao, Wenyue; Huang, Liang; Xiao, Min; Cao, Yang; Zhao, Lei; Wang, Na; Zhou, Jianfeng

    2018-06-14

    Chimeric antigen receptor T (CART) cell therapy has emerged as a potentially curative "drug" for cancer treatment. Cryopreservation of CART cells is necessary for their clinical application. Systematic studies on the effects of cryopreservation on the antitumor function of CART cells are lacking. Therefore, we compared the phenotypes and functions of CART cells that were cryopreserved during ex vivo expansion with those of freshly isolated populations. T cells expressing an anti-B-cell-maturation-antigen (BCMA) chimeric antigen receptor (CAR) were expanded in vitro for 10 days and then cryopreserved. After one month, the cells were resuscitated, and their transduction rates, apoptosis rates and cell subsets were examined via flow cytometry. The results indicated no significant changes in transduction rates or cell subsets, and the survival rate of the resuscitated cells was approximately 90% Furthermore, similar tumoricidal effects and degranulation functions of the resuscitated cells compared with normally cultured cells were verified by calcein release and CD107a assays. A NOD/SCID mouse model was used to estimate the differences in the in vivo antitumor effects of the cryopreserved and normally cultured T cells, but no significant differences were observed. Following co-culture with several target cell types, the cytokines released by the cryopreserved and normally cultured T cells were measured via enzyme-linked immunosorbent assays (ELISAs). The results revealed that the release of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was significantly decreased. These data demonstrated that with the exception of a decrease in cytokine release, the cryopreserved CART cells retained their antitumor functions. Copyright © 2018. Published by Elsevier Inc.

  18. Exosomes: the ideal nanovectors for biodelivery.

    PubMed

    Fais, Stefano; Logozzi, Mariantonia; Lugini, Luana; Federici, Cristina; Azzarito, Tommaso; Zarovni, Natasa; Chiesi, Antonio

    2013-01-01

    Nanomedicine aims to exploit the improved and often novel physical, chemical, and biological properties of materials at the nanometric scale, possibly with the highest level of biomimetism, an approach that simulates what occurs in nature. Although extracellularly released vesicles include both microvesicles (MVs) and exosomes, only exosomes have the size that may be considered suitable for potential use in nanomedicine. In fact, recent reports have shown that exosomes are able to interact with target cells within an organ or at a distance using different mechanisms. Much is yet to be understood about exosomes, and currently, we are looking at the visible top of an iceberg, with most of what we have to understand on these nanovesicles still under the sea. In fact, we know that exosomes released by normal cells always trigger positive effects, whereas those released by cells in pathological condition, such as tumor or infected cells, may induce undesired, dangerous, and mostly unknown effects, but we cannot exclude the possibility that exosomes may also be detrimental for the body in normal conditions. However, whether we consider extracellular vesicles as a whole, thus including MVs, it appears that even in normal conditions, extracellular vesicles may lead to unwanted effects, depending on gender and age. This review aims to critically emphasize existing data in the literature that support the possible roles of exosomes in both diagnostic and therapeutic scopes.

  19. Evaluation of Autologous Fascia Implantation With Controlled Release of Fibroblast Growth Factor for Recurrent Laryngeal Nerve Paralysis Due to Long-term Denervation.

    PubMed

    Nagai, Hiromi; Nishiyama, Koichiro; Seino, Yutomo; Tabata, Yasuhiko; Okamoto, Makito

    2016-06-01

    Paralyzed tissue due to long-term denervation is resistant to many treatments because it induces irreversible histological changes and disorders of deglutition or phonation. We sought to determine the effect of autologous transplantation of fascia into the vocal fold (ATFV) with controlled release of basic fibroblast growth factor (bFGF) on long-term unilateral vocal fold paralysis (UVFP). Unilateral recurrent laryngeal nerve (RLN) section was performed on 20 rats. Five rats were implanted with autologous fascia only (fascia group), and 10 rats were implanted with autologous fascia and a gelatin hydrogel sheet with 1 μg (1 μg bFGF + fascia group) or 0.1 μg (0.1 μg bFGF + fascia group) of bFGF 4 months after RLN section. We evaluated the normalized glottal gap and laryngeal volume and histological changes 3 months after implantation. The normalized glottal gap was significantly reduced in the 3 fascia implantation groups. Normalized laryngeal volume, fat volume, and lateral thyroarytenoid muscle volume were significantly increased in the 2 fascia implantation with bFGF groups. The ATFV with controlled release of bFGF repaired the glottal gap and laryngeal volume after RLN section and may reduce the occurrence of aspiration and hoarseness. We speculate that this treatment improves laryngeal function in long-term RLN denervation. © The Author(s) 2016.

  20. Acetylcholine Encodes Long-Lasting Presynaptic Plasticity at Glutamatergic Synapses in the Dorsal Striatum after Repeated Amphetamine Exposure

    PubMed Central

    Wang, Wengang; Darvas, Martin; Storey, Granville P.; Bamford, Ian J.; Gibbs, Jeffrey T.; Palmiter, Richard D.

    2013-01-01

    Locomotion and cue-dependent behaviors are modified through corticostriatal signaling whereby short-term increases in dopamine availability can provoke persistent changes in glutamate release that contribute to neuropsychiatric disorders, including Parkinson's disease and drug dependence. We found that withdrawal of mice from repeated amphetamine treatment caused a chronic presynaptic depression (CPD) in glutamate release that was most pronounced in corticostriatal terminals with a low probability of release and lasted >50 d in treated mice. An amphetamine challenge reversed CPD via a dopamine D1-receptor-dependent paradoxical presynaptic potentiation (PPP) that increased corticostriatal activity in direct pathway medium spiny neurons. This PPP was correlated with locomotor responses after a drug challenge, suggesting that it may underlie the sensitization process. Experiments in brain slices and in vivo indicated that dopamine regulation of acetylcholine release from tonically active interneurons contributes to CPD, PPP, locomotor sensitization, and cognitive ability. Therefore, a chronic decrease in corticostriatal activity during withdrawal is regulated around a new physiological range by tonically active interneurons and returns to normal upon reexposure to amphetamine, suggesting that this paradoxical return of striatal activity to a more stable, normalized state may represent an additional source of drug motivation during abstinence. PMID:23785153

  1. Octacosanol educes physico-chemical attributes, release and bioavailability as modified nanocrystals.

    PubMed

    Sen Gupta, Surashree; Ghosh, Mahua

    2017-10-01

    Octacosanol is a lesser known nutraceutical with the potential for treatment of several inflammatory diseases, high cholesterol, Parkinson's symptoms and tumour growth along with the capacity to improve athletic performance. But its lipophilicity and large structure inhibits extended solubility in water resulting in poor absorption and a low bioavailability. In the present work, sodium salt of octacosyl sulfate was synthesized. It displayed improved water solubility. Its nanocrystals, synthesized by means of nanoprecipitation technique, enhanced diffusion velocity, antioxidant capacity, shelf-life, penetrability and bioavailability. Particle size of the nanocrystals ranged between 197 and 220nm. Both modified octacosanol and its nanocrystals displayed maximum lipid peroxidation activities at a concentration 1000ppm, but nanocrystals demonstrated higher prevention. From freeze-thaw cycles it was evident that normal octacosanol crystals were far more prone to temperature variations than the nanocrystals. A pronounced increase in release/diffusion rate and bioavailability was observed for the nanocrystals of the modified octacosanol. In vitro release kinetics, bioavailability and bioequivalence were studied. Relative bioavailability for gastric passage and pancreatic passage of nanocrystals was 2.58 times and 1.81 times that of normal crystals respectively. Furthermore the nanocrystals displayed a superior in vitro release rate, while following a non-Fickian mode. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Anglers' beliefs about tag-and-release programs

    Treesearch

    Maureen P. Donnelly; Jerry J. Vaske

    1992-01-01

    Scientific research and the popular literature have emphasized the biological value of tag-and-release fishing. Relatively few publications, however, have examined the anglers' beliefs about the importance of this activity. This paper summarizes sport fishermen's behavior and attitudes related to tag-and-release programs. The data were collected from three...

  3. USDA National Nutrient Database for Standard Reference, release 28

    USDA-ARS?s Scientific Manuscript database

    The USDA National Nutrient Database for Standard Reference, Release 28 contains data for nearly 8,800 food items for up to 150 food components. SR28 replaces the previous release, SR27, originally issued in August 2014. Data in SR28 supersede values in the printed handbooks and previous electronic...

  4. Nateglinide

    MedlinePlus

    ... condition in which the body does not use insulin normally and therefore cannot control the amount of ... of glucose by stimulating the pancreas to release insulin.Over time, people who have diabetes and high ...

  5. Repaglinide

    MedlinePlus

    ... condition in which the body does not use insulin normally and, therefore, cannot control the amount of ... of glucose by stimulating the pancreas to release insulin.Over time, people who have diabetes and high ...

  6. Stress relaxation properties of four orthodontic aligner materials: A 24-hour in vitro study.

    PubMed

    Lombardo, Luca; Martines, Elisa; Mazzanti, Valentina; Arreghini, Angela; Mollica, Francesco; Siciliani, Giuseppe

    2017-01-01

    To investigate the stress release properties of four thermoplastic materials used to make orthodontic aligners when subjected to 24 consecutive hours of deflection. Four types of aligner materials (two single and two double layered) were selected. After initial yield strength testing to characterize the materials, each sample was subjected to a constant load for 24 hours in a moist, temperature-regulated environment, and the stress release over time was measured. The test was performed three times on each type of material. All polymers analyzed released a significant amount of stress during the 24-hour period. Stress release was greater during the first 8 hours, reaching a plateau that generally remained constant. The single-layer materials, F22 Aligner polyurethane (Sweden & Martina, Due Carrare, Padova, Italy) and Duran polyethylene terephthalate glycol-modified (SCHEU, Iserlohn, Germany), exhibited the greatest values for both absolute stress and stress decay speed. The double-layer materials, Erkoloc-Pro (Erkodent, Pfalzgrafenweiler, Germany) and Durasoft (SCHEU), exhibited very constant stress release, but at absolute values up to four times lower than the single-layer samples tested. Orthodontic aligner performance is strongly influenced by the material of their construction. Stress release, which may exceed 50% of the initial stress value in the early hours of wear, may cause significant changes in the behavior of the polymers at 24 hours from the application of orthodontic loads, which may influence programmed tooth movement.

  7. Characterization of wear debris from metal-on-metal hip implants during normal wear versus edge-loading conditions.

    PubMed

    Kovochich, Michael; Fung, Ernest S; Donovan, Ellen; Unice, Kenneth M; Paustenbach, Dennis J; Finley, Brent L

    2018-04-01

    Advantages of second-generation metal-on-metal (MoM) hip implants include low volumetric wear rates and the release of nanosized wear particles that are chemically inert and readily cleared from local tissue. In some patients, edge loading conditions occur, which result in higher volumetric wear. The objective of this study was to characterize the size, morphology, and chemistry of wear particles released from MoM hip implants during normal (40° angle) and edge-loading (65° angle with microseparation) conditions. The mean primary particle size by volume under normal wear was 35 nm (range: 9-152 nm) compared with 95 nm (range: 6-573 nm) under edge-loading conditions. Hydrodynamic diameter analysis by volume showed that particles from normal wear were in the nano- (<100 nm) to submicron (<1000 nm) size range, whereas edge-loading conditions generated particles that ranged from <100 nm up to 3000-6000 nm in size. Particles isolated from normal wear were primarily chromium (98.5%) and round to oval in shape. Edge-loading conditions generated more elongated particles (4.5%) (aspect ratio ≥ 2.5) and more CoCr alloy particles (9.3%) compared with normal wear conditions (1.3% CoCr particles). By total mass, edge-loading particles contained approximately 640-fold more cobalt than normal wear particles. Our findings suggest that high wear conditions are a potential risk factor for adverse local tissue effects in MoM patients who experience edge loading. This study is the first to characterize both the physical and chemical characteristics of MoM wear particles collected under normal and edge-loading conditions. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 986-996, 2018. © 2017 Wiley Periodicals, Inc.

  8. Risk analysis for dry snow slab avalanche release by skier triggering

    NASA Astrophysics Data System (ADS)

    McClung, David

    2013-04-01

    Risk analysis is of primary importance for skier triggering of avalanches since human triggering is responsible for about 90% of deaths from slab avalanches in Europe and North America. Two key measureable quantities about dry slab avalanche release prior to initiation are the depth to the weak layer and the slope angle. Both are important in risk analysis. As the slope angle increases, the probability of avalanche release increases dramatically. As the slab depth increases, the consequences increase if an avalanche releases. Among the simplest risk definitions is (Vick, 2002): Risk = (Probability of failure) x (Consequences of failure). Here, these two components of risk are the probability or chance of avalanche release and the consequences given avalanche release. In this paper, for the first time, skier triggered avalanches were analyzed from probability theory and its relation to risk for both the D and . The data consisted of two quantities : (,D) taken from avalanche fracture line profiles after an avalanche has taken place. Two data sets from accidentally skier triggered avalanches were considered: (1) 718 for and (2) a set of 1242 values of D which represent average values along the fracture line. The values of D were both estimated (about 2/3) and measured (about 1/3) by ski guides from Canadian Mountain Holidays CMH). I also analyzed 1231 accidentally skier triggered avalanches reported by CMH ski guides for avalanche size (representing destructive potential) on the Canadian scale. The size analysis provided a second analysis of consequences to verify that using D. The results showed that there is an intermediate range of both D and with highest risk. ForD, the risk (product of consequences and probability of occurrence) is highest for D in the approximate range 0.6 m - 1.0 m. The consequences are low for lower values of D and the chance of release is low for higher values of D. Thus, the highest product is in the intermediate range. For slope angles, the risk analysis showed there are two ranges: ˜ 320; × 460for which risk is lowest. In this case, both the range of and the consequences vary by about a factor of two so the probability of release dominates the risk analysis to yield low risk at the tails of the distribution of with highest risk in the middle (330 - 450) of the expected range (250 - 550).

  9. The Idea of a Normal University in the 21st Century

    ERIC Educational Resources Information Center

    Hayhoe, Ruth; Li, Jun

    2010-01-01

    The establishment of normal colleges and universities is an important component of building a modern country, which possesses different value ethos with the universities. The emergence of the Ecole Normale Superieure in Paris and the local normal schools has set a new model for teacher education around the world and promoted values and knowledge…

  10. Amantadine Ameliorates Dopamine-Releasing Deficits and Behavioral Deficits in Rats after Fluid Percussion Injury

    PubMed Central

    Huang, Eagle Yi-Kung; Tsui, Pi-Fen; Kuo, Tung-Tai; Tsai, Jing-Jr.; Chou, Yu-Ching; Ma, Hsin-I; Chiang, Yung-Hsiao; Chen, Yuan-Hao

    2014-01-01

    Aims To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery. Materials and Methods In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury. Results Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion. Conclusion Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury. PMID:24497943

  11. Consequences of phosphorus interactions with calcium, phytase, and cholecalciferol on zootechnical performance and mineral retention in broiler chickens.

    PubMed

    Delezie, E; Maertens, L; Huyghebaert, G

    2012-10-01

    The objective was to determine the effect of calcium (Ca), total phosphorus (Ptot), cholecalciferol, and phytase level in the diet on the performance, tibia ash percentage, and Ca and P retention in broilers until slaughter age. Broilers were randomly assigned to 12 treatments, each with 6 replicates, comprising 3 diets differing in Ca and P level: 1) normal Ca and Ptot level (NN); 2) normal Ca and low Ptot level (NL), 3) low Ca and Ptot level (LL). Broilers were also given 2 levels of cholecalciferol and 2 levels of phytase. The normal levels of Ca and Ptot for the starter, grower, and finisher phases were 0.90, 0.82, 0.74% and 0.67, 0.62, 0.57%, respectively. The low Ca and Ptot levels for the 3 phases were 0.67, 0.60, 0.52% and 0.57, 0.51, 0.46%, respectively. Broilers of the NL treatment obtained the lowest BW, whereas BW of the NN and LL groups were comparable. Cholecalciferol significantly affected the BW, with differences up to 2.6 and 1.2% for the starter and grower phases, respectively. The highest cholecalciferol effect was found in combination with the NN treatment. The percentage of retained Ca increased from 33% to 41% and 48% when the imbalanced diet was replaced by the NN and LL balanced diets, respectively. P release from phytate was 64 and 67% for the NL and LL diets, respectively. Phytase and cholecalciferol had significantly favorable effects on retention values but these effects were dependent on Ca and Ptot levels and their ratio. In conclusion, both diets with the balanced Ca/Ptot ratio resulted in the best performance, highest tibia ash percentage and P release from phytate. A reduction of the Aviagen (2009) recommended P requirements by 25 to 30% and Ca by 15 to 20% over the various phases did not negatively affect performance, bone development, and improved Ca and Ptot retention. The effects of supplementing cholecalciferol and phytase were additive but not significant and no synergism between both was present.

  12. Strain energy release rate analysis of the end-notched flexure specimen using the finite-element method

    NASA Technical Reports Server (NTRS)

    Salpekar, S. A.; Raju, I. S.; O'Brien, T. K.

    1988-01-01

    Two-dimensional finite-element analysis of the end-notched flexure specimen was performed using 8-node isoparametric, parabolic elements to evaluate compliance and mode II strain energy release rates, G sub II. The G sub II values were computed using two different techniques: the virtual crack-closure technique (VCCT) and the rate of change of compliance with crack length (compliance derivative method). The analysis was performed for various crack-length-to-semi-span (a/L) ratios ranging from 0.2 to 0.9. Three material systems representing a wide range of material properties were analyzed. The compliance and strain energy release rates of the specimen calculated with the present finite-element analysis agree very well with beam theory equations including transverse shear. The G sub II values calculated using the compliance derivative method compared extremely well with those calculated using the VCCT. The G sub II values obtained by the compliance derivative method using the top or bottom beam deflections agreed closely with each other. The strain energy release rates from a plane-stress analysis were higher than the plane-strain values by only a small percentage, indicating that either assumption may be used in the analysis. The G sub II values for one material system calculated from the finte-element analysis agreed with one solution in the literature and disagreed with the other solution in the literature.

  13. Strain-energy-release rate analysis of the end-notched flexure specimen using the finite-element method

    NASA Technical Reports Server (NTRS)

    Salpekar, S. A.; Raju, I. S.; Obrien, T. K.

    1987-01-01

    Two-dimensional finite-element analysis of the end-notched flexure specimen was performed using 8-node isoparametric, parabolic elements to evaluate compliance and mode II strain energy release rates, G sub II. The G sub II values were computed using two different techniques: the virtural crack-closure technique (VCCT) and the rate of change of compliance with crack length (compliance derivative method). The analysis was performed for various crack-length-to-semi-span (a/L) ratios ranging from 0.2 to 0.9. Three material systems representing a wide range of material properties were analyzed. The compliance and strain energy release rates of the specimen calculated with the present finite-element analysis agree very well with beam theory equations including transverse shear. The G sub II values calculated using the compliance derivative method compared extremely well with those calculated using the VCCT. The G sub II values obtained by the compliance derivative method using the top or bottom beam deflections agreed closely with each other. The strain energy release rates from a plane-stress analysis were higher than the plane-strain values by only a small percentage, indicating that either assumption may be used in the analysis. The G sub II values for one material system calculated from the finite-element analysis agreed with one solution in the literature and disagreed with the other solution in the literature.

  14. Flavonoid Values for USDA Survey Foods and Beverages 2007-2008: Provisional Flavonoid Addendum, FNDDS 4.1 and Flavonoid Intake Data, WWEIA, NHANES 2007-2008

    USDA-ARS?s Scientific Manuscript database

    This release of the Flavonoid Values for Survey Foods and Beverages 2007-2008 makes possible, for the first time, calculation of flavonoid intakes based on all foods and beverages reported in national surveys. This release has two components. The first component is an addendum to USDA’s Food and N...

  15. Subacute thyroiditis

    MedlinePlus

    ... may release too little hormone, causing symptoms of hypothyroidism , including: Cold intolerance Constipation Fatigue Weight gain Dry ... often returns to normal. But in rare cases, hypothyroidism may be permanent. Exams and Tests Laboratory tests ...

  16. [Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people].

    PubMed

    Korkushko, O V; Lapin, B A; Goncharova, N D; Khavinson, V Kh; Shatilo, V B; Vengerin, A A; Antoniuk-Shcheglova, I A; Magdich, L V

    2007-01-01

    In the course of aging both monkeys and people reveal decreased night and average daily level of melatonin in the blood plasma and reduced hormone circadian rhythm amplitude, which evidence the disorder of the pineal gland melatonin releasing function. Peptide preparations of the pineal gland (Epithalamin--a complex of peptides isolated from the pineal gland and Epitalon--synthetic tetrapeptide) recover night release of endogenous melatonin and lead to the normalization of the hormone circadian rhythm in the blood plasma. In elderly people Epithalamin and Epitalon modulate pineal gland functional state: people with pineal gland functional insufficiency report an increase of night melatonin level. The preparations of the pineal gland, effectively increasing melatonin concentration and having no side effects, can be used in clinical geriatric practice.

  17. Experimental study on the cool storage performance of super absorbent polymers for cool storage clothes

    NASA Astrophysics Data System (ADS)

    Li, Shidong; Mo, Caisong; Wang, Junze; Zheng, Jingfu; Tian, Ruhong

    2017-11-01

    In this paper, a kind of cool storage clothes which can cool the human body in high temperature condition is put forward. super absorbent polymers was selected as a cold storage material, through at the normal and extreme environment simulation, the cold storage materials were prepared with different composition, and their performance was tested. Test results show that:under normal temperature conditions, the 1:50 concentration of super absorbent polymers continued to release the longest cooling time, compared with pure water, cooling time extended 43 minutes by about 30%; under the condition of 37°C, the 1:100 concentration of super absorbent polymers continued to release the longest cooling time, compared with pure water, cooling time extended 105 minutes by about 50%.

  18. Tomosyn-2 is required for normal motor performance in mice and sustains neurotransmission at motor endplates.

    PubMed

    Geerts, Cornelia J; Plomp, Jaap J; Koopmans, Bastijn; Loos, Maarten; van der Pijl, Elizabeth M; van der Valk, Martin A; Verhage, Matthijs; Groffen, Alexander J A

    2015-07-01

    Tomosyn-1 (STXBP5) is a soluble NSF attachment protein receptor complex-binding protein that inhibits vesicle fusion, but the role of tomosyn-2 (STXBP5L) in the mammalian nervous system is still unclear. Here we generated tomosyn-2 null (Tom2(KO/KO)) mice, which showed impaired motor performance. This was accompanied by synaptic changes at the neuromuscular junction, including enhanced spontaneous acetylcholine release frequency and faster depression of muscle motor endplate potentials during repetitive stimulation. The postsynaptic geometric arrangement and function of acetylcholine receptors were normal. We conclude that tomosyn-2 supports motor performance by regulation of transmitter release willingness to sustain synaptic strength during high-frequency transmission, which makes this gene a candidate for involvement in neuromuscular disorders.

  19. Disposable swim diaper retention of Cryptosporidium-sized particles on human subjects in a recreational water setting.

    PubMed

    Amburgey, James E; Anderson, J Brian

    2011-12-01

    Cryptosporidium is a chlorine-resistant protozoan parasite responsible for the majority of waterborne disease outbreaks in recreational water venues in the USA. Swim diapers are commonly used by diaper-aged children participating in aquatic activities. This research was intended to evaluate disposable swim diapers for retaining 5-μm diameter polystyrene microspheres, which were used as non-infectious surrogates for Cryptosporidium oocysts. A hot tub recirculating water without a filter was used for this research. The microsphere concentration in the water was monitored at regular intervals following introduction of microspheres inside of a swim diaper while a human subject undertook normal swim/play activities. Microsphere concentrations in the bulk water showed that the majority (50-97%) of Cryptosporidium-sized particles were released from the swim diaper within 1 to 5 min regardless of the swim diaper type or configuration. After only 10 min of play, 77-100% of the microspheres had been released from all swim diapers tested. This research suggests that the swim diapers commonly used by diaper-aged children in swimming pools and other aquatic activities are of limited value in retaining Cryptosporidium-sized particles. Improved swim diaper solutions are necessary to efficiently retain pathogens and effectively safeguard public health in recreational water venues.

  20. Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione.

    PubMed

    Marchionatti, Ana M; Perez, Adriana V; Diaz de Barboza, Gabriela E; Pereira, Beatriz M; Tolosa de Talamoni, Nori G

    2008-02-01

    Menadione (MEN) inhibits intestinal calcium absorption by a mechanism not completely understood. The aim of this work was to find out the role of mitochondria in this inhibitory mechanism. Hence, normal chicks treated with one i.p. dose of MEN were studied in comparison with controls. Intestinal calcium absorption was measured by the in situ ligated intestinal segment technique. GSH, oxidoreductase activities from the Krebs cycle and enzymes of the antioxidant system were measured in isolated mitochondria. Mitochondrial membrane potential was measured by a flow cytometer technique. DNA fragmentation and cytochrome c localization were determined by immunocytochemistry. Data indicate that in 30 min, MEN decreases intestinal Ca(2+) absorption, which returns to the control values after 10 h. GSH was only decreased for half an hour, while the activity of malate dehydrogenase and alpha-ketoglutarate dehydrogenase was diminished for 48 h. Mn(2+)-superoxide dismutase activity was increased in 30 min, whereas the activity of catalase and glutathione peroxidase remained unaltered. DNA fragmentation and cytochrome c release were maximal in 30 min, but were recovered after 15 h. In conclusion, MEN inhibits intestinal Ca(2+) absorption by mitochondrial dysfunction as revealed by GSH depletion and alteration of the permeability triggering the release of cytochrome c and DNA fragmentation.

  1. High contents of rare earth elements (REEs) in stream waters of a Cu-Pb-Zn mining area.

    PubMed

    Protano, G; Riccobono, F

    2002-01-01

    Stream waters draining an old mining area present very high rare earth element (REE) contents, reaching 928 microg/l as the maximum total value (sigmaREE). The middle rare earth elements (MREEs) are usually enriched with respect to both the light (LREEs) and heavy (HREEs) elements of this group, producing a characteristic "roof-shaped" pattern of the shale Post-Archean Australian Shales-normalized concentrations. At the Fenice Capanne Mine (FCM), the most important base metal mine of the study area, the REE source coincides with the mine tailings, mostly the oldest ones composed of iron-rich materials. The geochemical history of the REEs released into Noni stream from wastes in the FCM area is strictly determined by the pH, which controls the REE speciation and in-stream processes. The formation of Al-rich and mainly Fe-rich flocs effectively scavenges the REEs, which are readily and drastically removed from the solution when the pH approaches neutrality. Leaching experiments performed on flocs and waste materials demonstrate that Fe-oxides/oxyhydroxides play a key role in the release of lanthanide elements into stream waters. The origin of the "roof-shaped" REE distribution pattern as well as the peculiar geochemical behavior of some lanthanide elements in the aqueous system are discussed.

  2. Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in Patients with Schizophrenia.

    PubMed

    Abdul Wahab, Noor Alaudin; Zakaria, Mohd Normani; Abdul Rahman, Abdul Hamid; Sidek, Dinsuhaimi; Wahab, Suzaily

    2017-11-01

    The present, case-control, study investigates binaural hearing performance in schizophrenia patients towards sentences presented in quiet and noise. Participants were twenty-one healthy controls and sixteen schizophrenia patients with normal peripheral auditory functions. The binaural hearing was examined in four listening conditions by using the Malay version of hearing in noise test. The syntactically and semantically correct sentences were presented via headphones to the randomly selected subjects. In each condition, the adaptively obtained reception thresholds for speech (RTS) were used to determine RTS noise composite and spatial release from masking. Schizophrenia patients demonstrated significantly higher mean RTS value relative to healthy controls (p=0.018). The large effect size found in three listening conditions, i.e., in quiet (d=1.07), noise right (d=0.88) and noise composite (d=0.90) indicates statistically significant difference between the groups. However, noise front and noise left conditions show medium (d=0.61) and small (d=0.50) effect size respectively. No statistical difference between groups was noted in regards to spatial release from masking on right (p=0.305) and left (p=0.970) ear. The present findings suggest an abnormal unilateral auditory processing in central auditory pathway in schizophrenia patients. Future studies to explore the role of binaural and spatial auditory processing were recommended.

  3. A mRNA-Responsive G-Quadruplex-Based Drug Release System

    PubMed Central

    Yaku, Hidenobu; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

    2015-01-01

    G-quadruplex-based drug delivery carriers (GDDCs) were designed to capture and release a telomerase inhibitor in response to a target mRNA. Hybridization between a loop on the GDDC structure and the mRNA should cause the G-quadruplex structure of the GDDC to unfold and release the bound inhibitor, anionic copper(II) phthalocyanine (CuAPC). As a proof of concept, GDDCs were designed with a 10-30-mer loop, which can hybridize with a target sequence in epidermal growth factor receptor (EGFR) mRNA. Structural analysis using circular dichroism (CD) spectroscopy showed that the GDDCs form a (3 + 1) type G-quadruplex structure in 100 mM KCl and 10 mM MgCl2 in the absence of the target RNA. Visible absorbance titration experiments showed that the GDDCs bind to CuAPC with Ka values of 1.5 × 105 to 5.9 × 105 M−1 (Kd values of 6.7 to 1.7 μM) at 25 °C, depending on the loop length. Fluorescence titration further showed that the G-quadruplex structure unfolds upon binding to the target RNA with Ka values above 1.0 × 108 M−1 (Kd values below 0.01 μM) at 25 °C. These results suggest the carrier can sense and bind to the target RNA, which should result in release of the bound drug. Finally, visible absorbance titration experiments demonstrated that the GDDC release CuAPC in response to the target RNA. PMID:25905703

  4. Germination parameterization and development of an after-ripening thermal-time model for primary dormancy release of Lithospermum arvense seeds.

    PubMed

    Chantre, Guillermo R; Batlla, Diego; Sabbatini, Mario R; Orioli, Gustavo

    2009-06-01

    Models based on thermal-time approaches have been a useful tool for characterizing and predicting seed germination and dormancy release in relation to time and temperature. The aims of the present work were to evaluate the relative accuracy of different thermal-time approaches for the description of germination in Lithospermum arvense and to develop an after-ripening thermal-time model for predicting seed dormancy release. Seeds were dry-stored at constant temperatures of 5, 15 or 24 degrees C for up to 210 d. After different storage periods, batches of 50 seeds were incubated at eight constant temperature regimes of 5, 8, 10, 13, 15, 17, 20 or 25 degrees C. Experimentally obtained cumulative-germination curves were analysed using a non-linear regression procedure to obtain optimal population thermal parameters for L. arvense. Changes in these parameters were described as a function of after-ripening thermal-time and storage temperature. The most accurate approach for simulating the thermal-germination response of L. arvense was achieved by assuming a normal distribution of both base and maximum germination temperatures. The results contradict the widely accepted assumption of a single T(b) value for the entire seed population. The after-ripening process was characterized by a progressive increase in the mean maximum germination temperature and a reduction in the thermal-time requirements for germination at sub-optimal temperatures. The after-ripening thermal-time model developed here gave an acceptable description of the observed field emergence patterns, thus indicating its usefulness as a predictive tool to enhance weed management tactics.

  5. Unusual neutral oligosaccharides in mature Sindbis virus glycoproteins are synthesized from truncated precursor oligosaccharides in Chinese hamster ovary cells.

    PubMed

    Davidson, S K; Hunt, L A

    1983-03-01

    We have previously demonstrated the presence of unusual small asparaginyl-oligosaccharides [(Man)3GlcNAc2-ASN] in the mature glycoproteins of Sindbis virus released from both wild-type and lectin-resistant Chinese hamster ovary cells, but the mechanism of synthesis of these structures was not determined. Gel filtration and endo-beta-N-acetylglucosaminidase analyses of Pronase-digested glycopeptides from [3H]mannose-labelled Sindbis virus released at different times after infection of a phytohaemagglutinin-resistant line of Chinese hamster ovary cells demonstrated that these small asparaginyl-oligosaccharides were present in similar relative amounts in virus released throughout the virus infection, rather than arising primarily at late times when cytopathic effects were maximal. Similar analyses of pulse-labelled, cell-associated viral glycopeptides suggested that these small oligosaccharides on mature virus glycoprotein resulted from the normal alpha 1,2-mannosidase processing of truncated precursor oligosaccharides (containing five rather than nine mannoses), rather than from aberrant processing or degradation of the full-size precursor oligosaccharides or normal intermediates.

  6. Dynamics of neuroendocrine stress response: bistability, timing, and control of hypocortisolism

    NASA Astrophysics Data System (ADS)

    D'Orsogna, Maria; Chou, Tom; Kim, Lae

    The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in its activity are correlated with stress-related diseases such as post-traumatic stress disorder (PTSD) and major depressive disorder. We characterize ``normal'' and ``diseased'' states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), by circulating glucocorticoids such as cortisol (CORT). Our model includes ultradian oscillations, CRH self-upregulation of CRH release, and distinguishes two components of negative feedback by cortisol on circulating CRH levels: a slow direct suppression of CRH synthesis and a fast indirect effect on CRH release. The slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. We find that the timing of traumatic events may be an important factor in determining if and how the hallmarks of depressive disorders will manifest. Our model also suggests a mechanism whereby exposure therapy of stress disorders may act to normalize downstream dysregulation of the HPA axis.

  7. Free acetate production by rat hepatocytes during peroxisomal fatty acid and dicarboxylic acid oxidation.

    PubMed

    Leighton, F; Bergseth, S; Rørtveit, T; Christiansen, E N; Bremer, J

    1989-06-25

    The fate of the acetyl-CoA units released during peroxisomal fatty acid oxidation was studied in isolated hepatocytes from normal and peroxisome-proliferated rats. Ketogenesis and hydrogen peroxide generation were employed as indicators of mitochondrial and peroxisomal fatty acid oxidation, respectively. Butyric and hexanoic acids were employed as mitochondrial substrates, 1, omega-dicarboxylic acids as predominantly peroxisomal substrates, and lauric acid as a substrate for both mitochondria and peroxisomes. Ketogenesis from dicarboxylic acids was either absent or very low in normal and peroxisome-proliferated hepatocytes, but free acetate release was detected at rates that could account for all the acetyl-CoA produced in peroxisomes by dicarboxylic and also by monocarboxylic acids. Mitochondrial fatty acid oxidation also led to free acetate generation but at low rates relative to ketogenesis. The origin of the acetate released was confirmed employing [1-14C]dodecanedioic acid. Thus, the activity of peroxisomes might contribute significantly to the free acetate generation known to occur during fatty acid oxidation in rats and possibly also in humans.

  8. Release of the antioxidants ascorbate and urate from a nitrergically-innervated smooth muscle.

    PubMed

    Lilley, E; Gibson, A

    1997-12-01

    1. The main object of the present study was to determine whether ascorbate, an antioxidant which has been shown to protect nitric oxide (NO) from attack by scavenger molecules, might be released from nitrergically-innervated smooth muscle; ascorbate release from the rat anococcygeus was measured by use of h.p.l.c. with electrochemical detection. 2. Incubation of rat anococcygeus muscles in normal physiological salt solution (PSS; 30 min) resulted in release of ascorbate into the bathing medium (7.7 +/- 0.9 nmol g-1 tissue). This release was increased by 96% when muscles were incubated in high K+ (70 mM) PSS. The resting release of ascorbate was unaffected by tetrodotoxin (TTX; 1 microM), omega-conotoxin GVIA (10 nM) or omission of calcium ions from the PSS (with addition of 0.2 mM EGTA), but all three procedures attenuated the increased release observed under depolarizing conditions. Resting release of ascorbate was unaffected by glutamate (100 microM), aspartate (100 microM), gamma-aminobutyric acid (100 microM) or carbachol (50 microM). 3. A second h.p.l.c. peak, which always preceded the ascorbate peak, was identified as urate. Urate release from the anococcygeus, following 30 min incubation in normal PSS, was 64.6 +/- 12.7 nmol g-1 tissue but, unlike ascorbate, urate release was unchanged in high K+ PSS. In functional experiments, urate (100-400 microM) partially protected NO (15 microM)-induced relaxations of the rat anococcygeus from inhibition by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO; 50 microM), but not from inhibition by hydroquinone or duroquinone (both 100 microM). 4. Muscles chemically sympathectomized with 6-hydroxydopamine (6-OHDA, 500 microM; 2 h) still exhibited release of ascorbate (2.5 +/- 0.4 nmol g-1 tissue) and urate (22.2 +/- 2.9 nmol g-1 tissue); in both cases the release was similar to that observed in time-matched control tissues not exposed to 6-OHDA. High K+ PSS produced a TTX-sensitive increase in release of ascorbate, but not urate, from 6-OHDA-treated muscles. 5. The results demonstrate that significant amounts of ascorbate and urate are released from the rat anococcygeus muscle. Ascorbate, but not urate, release appears to be enhanced by activation of nerves which are resistant to 6-OHDA pretreatment. Since both antioxidants can protect NO from attack by scavenger molecules, their release in nitrergically-innervated tissues may be important for the provision of the correct redox environment to allow NO to fulfill its proposed neurotransmitter role.

  9. The Concentrations of Circulating Plasma Oxytocin and the Pattern of Oxytocin Release in Mare during Oestrus and after Ovulation

    NASA Astrophysics Data System (ADS)

    Bae, Sung Eun

    Mares susceptible to persistent mating-induced endometritis (PMIE) accumulate intrauterine fluid after mating. One of the factors causing delayed uterine clearance is thought to be impaired uterine contractility. Oxytocin is central in controlling myometrial contractility. The objective of the present study was to describe peripheral oxytocin release during estrus and in the early postovulatory period in reproductively-normal mares and to compare the baseline circulating oxytocin concentrations in reproductively-normal mares and mares with PMIE. Blood samples were collected from reproductively-normal mares (n=5) from day -5 of estrus to day 2 postovulation and every 5 min for 30 min from reproductively-normal mares (n=5) and mares with PMIE (n=5) on day 3 of estrus. Pulsatile secretion of oxytocin was observed in all mares. Mean plasma oxytocin concentrations were significantly higher (P<0.05) in estrus (day -5 to day -2) than on the day of ovulation (day 0). After ovulation, plasma oxytocin concentrations tended to increase. On day 3 of estrus, plasma oxytocin concentrations were significantly higher (P<0.01) in reproductively-normal mares than in mares with PMIE. The results showed there is a significant difference in plasma oxytocin concentrations between mares to PMIE. The low plasma oxytocin concentrations in mares with PMIE may contribute to predisposing factors in their poor uterine clearance in these mares.

  10. Feasibility of Computed Tomography-Guided Methods for Spatial Normalization of Dopamine Transporter Positron Emission Tomography Image.

    PubMed

    Kim, Jin Su; Cho, Hanna; Choi, Jae Yong; Lee, Seung Ha; Ryu, Young Hoon; Lyoo, Chul Hyoung; Lee, Myung Sik

    2015-01-01

    Spatial normalization is a prerequisite step for analyzing positron emission tomography (PET) images both by using volume-of-interest (VOI) template and voxel-based analysis. Magnetic resonance (MR) or ligand-specific PET templates are currently used for spatial normalization of PET images. We used computed tomography (CT) images acquired with PET/CT scanner for the spatial normalization for [18F]-N-3-fluoropropyl-2-betacarboxymethoxy-3-beta-(4-iodophenyl) nortropane (FP-CIT) PET images and compared target-to-cerebellar standardized uptake value ratio (SUVR) values with those obtained from MR- or PET-guided spatial normalization method in healthy controls and patients with Parkinson's disease (PD). We included 71 healthy controls and 56 patients with PD who underwent [18F]-FP-CIT PET scans with a PET/CT scanner and T1-weighted MR scans. Spatial normalization of MR images was done with a conventional spatial normalization tool (cvMR) and with DARTEL toolbox (dtMR) in statistical parametric mapping software. The CT images were modified in two ways, skull-stripping (ssCT) and intensity transformation (itCT). We normalized PET images with cvMR-, dtMR-, ssCT-, itCT-, and PET-guided methods by using specific templates for each modality and measured striatal SUVR with a VOI template. The SUVR values measured with FreeSurfer-generated VOIs (FSVOI) overlaid on original PET images were also used as a gold standard for comparison. The SUVR values derived from all four structure-guided spatial normalization methods were highly correlated with those measured with FSVOI (P < 0.0001). Putaminal SUVR values were highly effective for discriminating PD patients from controls. However, the PET-guided method excessively overestimated striatal SUVR values in the PD patients by more than 30% in caudate and putamen, and thereby spoiled the linearity between the striatal SUVR values in all subjects and showed lower disease discrimination ability. Two CT-guided methods showed comparable capability with the MR-guided methods in separating PD patients from controls and showed better correlation between putaminal SUVR values and the parkinsonian motor severity than the PET-guided method. CT-guided spatial normalization methods provided reliable striatal SUVR values comparable to those obtained with MR-guided methods. CT-guided methods can be useful for analyzing dopamine transporter PET images when MR images are unavailable.

  11. Feasibility of Computed Tomography-Guided Methods for Spatial Normalization of Dopamine Transporter Positron Emission Tomography Image

    PubMed Central

    Kim, Jin Su; Cho, Hanna; Choi, Jae Yong; Lee, Seung Ha; Ryu, Young Hoon; Lyoo, Chul Hyoung; Lee, Myung Sik

    2015-01-01

    Background Spatial normalization is a prerequisite step for analyzing positron emission tomography (PET) images both by using volume-of-interest (VOI) template and voxel-based analysis. Magnetic resonance (MR) or ligand-specific PET templates are currently used for spatial normalization of PET images. We used computed tomography (CT) images acquired with PET/CT scanner for the spatial normalization for [18F]-N-3-fluoropropyl-2-betacarboxymethoxy-3-beta-(4-iodophenyl) nortropane (FP-CIT) PET images and compared target-to-cerebellar standardized uptake value ratio (SUVR) values with those obtained from MR- or PET-guided spatial normalization method in healthy controls and patients with Parkinson’s disease (PD). Methods We included 71 healthy controls and 56 patients with PD who underwent [18F]-FP-CIT PET scans with a PET/CT scanner and T1-weighted MR scans. Spatial normalization of MR images was done with a conventional spatial normalization tool (cvMR) and with DARTEL toolbox (dtMR) in statistical parametric mapping software. The CT images were modified in two ways, skull-stripping (ssCT) and intensity transformation (itCT). We normalized PET images with cvMR-, dtMR-, ssCT-, itCT-, and PET-guided methods by using specific templates for each modality and measured striatal SUVR with a VOI template. The SUVR values measured with FreeSurfer-generated VOIs (FSVOI) overlaid on original PET images were also used as a gold standard for comparison. Results The SUVR values derived from all four structure-guided spatial normalization methods were highly correlated with those measured with FSVOI (P < 0.0001). Putaminal SUVR values were highly effective for discriminating PD patients from controls. However, the PET-guided method excessively overestimated striatal SUVR values in the PD patients by more than 30% in caudate and putamen, and thereby spoiled the linearity between the striatal SUVR values in all subjects and showed lower disease discrimination ability. Two CT-guided methods showed comparable capability with the MR-guided methods in separating PD patients from controls and showed better correlation between putaminal SUVR values and the parkinsonian motor severity than the PET-guided method. Conclusion CT-guided spatial normalization methods provided reliable striatal SUVR values comparable to those obtained with MR-guided methods. CT-guided methods can be useful for analyzing dopamine transporter PET images when MR images are unavailable. PMID:26147749

  12. Electrical Stimuli Are Anti-Apoptotic in Skeletal Muscle via Extracellular ATP. Alteration of This Signal in Mdx Mice Is a Likely Cause of Dystrophy

    PubMed Central

    Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

    2013-01-01

    ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies. PMID:24282497

  13. Electrical stimuli are anti-apoptotic in skeletal muscle via extracellular ATP. Alteration of this signal in Mdx mice is a likely cause of dystrophy.

    PubMed

    Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

    2013-01-01

    ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies.

  14. Energy transformation, transfer, and release dynamics in high speed turbulent flows

    DTIC Science & Technology

    2017-03-01

    experimental techniques developed allowed non -intrusive measurement of convecting velocity fields in supersonic flows and used for validation of LES of...by the absence of (near-)normal shocks that normal injection generates. New experimental techniques were developed that allowed the non -intrusive...and was comprised of several parts in which significant accomplishments were made: 1. An experimental effort focusing on investigations in: a

  15. Seeing the Talker's Face Improves Free Recall of Speech for Young Adults with Normal Hearing but Not Older Adults with Hearing Loss

    ERIC Educational Resources Information Center

    Rudner, Mary; Mishra, Sushmit; Stenfelt, Stefan; Lunner, Thomas; Rönnberg, Jerker

    2016-01-01

    Purpose: Seeing the talker's face improves speech understanding in noise, possibly releasing resources for cognitive processing. We investigated whether it improves free recall of spoken two-digit numbers. Method: Twenty younger adults with normal hearing and 24 older adults with hearing loss listened to and subsequently recalled lists of 13…

  16. Changes in NMR relaxation times of adjacent muscle after implantation of malignant and normal tissue.

    PubMed Central

    Ling, C. R.; Foster, M. A.; Mallard, J. R.

    1979-01-01

    In separate experiments, normal foreign tissue and malignant tumour were implanted s.c. into the rat thigh. NMR T1 values of the adjacent normal muscle, resulting from local inflammatory reactions or from malignant invasion, were measured. Elevations in T1 of the underlying muscle occurred within 24 h in both experiments, and it is believed these were caused by rapid inflammatory and immunological reactions to the implants. However the T1 values of muscle samples adjacent to the non-malignant implants decreased during the 11 days after implantation, dropping to values within the normal range. In the second experiment there was progressive malignant invasion into the normal adjacent tissue and the elevated T1 values were maintained throughout the 12-day period. The effects of the implantation on tissue water content are discussed in relation to NMR T1 relaxation times, and the relevance to whole-body NMR imaging of elevated T1 values due to nonmalignant pathological states is considered. PMID:526431

  17. Controlled Release of Imidacloprid from Poly Styrene-Diacetone - Nanoformulation

    NASA Astrophysics Data System (ADS)

    Qian, Kun; Guo, Yanzhen; He, Lin

    2012-01-01

    Imidacloprid is a neonicotinoids insecticide, which is important for the cash crops such as tomato, rape and so on. The conventional formulation does not only increase the loss of pesticide but also leads to environmental pollution. Controlled-release formulations of pesticide are highly desirable not only for attaining the most effective utilization of the pesticide, but also for reducing environmental pollution. Pesticide imidacloprid was incorporated in poly (styrene-diacetone crylamide)-based formulation to obtain controlled release properties, and the imidacloprid nanocontrolled release formulation was characterized by infrared (IR) and field emission scanning electron microscope (FESEM). Factors related to loading efficiency, swelling and release behaviors of the formulation were investigated. It showed that the loading efficiency could reach about 40% (w/w). The values for the diffusion exponent "n" were in the range of 0.31-0.58, which indicated that the release of imidacloprid was diffusion-controlled. The time taken for 50% of the active ingredient to be released into water, T50, was also calculated for the comparison of formulations in different conditions. The results showed that the formulation with higher temperature and more diacetone crylamide had lower value of T50, which means a quicker release of the active ingredient. This study highlighted some pieces of evidence that improved pesticide incorporation and slower release were linked to potential interactions between the pesticide and the polymer.

  18. Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats.

    PubMed

    Fediuc, Sergiu; Campbell, Jonathan E; Riddell, Michael C

    2006-06-01

    Adaptations of the hypothalamic-pituitary-adrenal (HPA) axis to voluntary exercise in rodents are not clear, because most investigations use forced-exercise protocols, which are associated with psychological stress. In the present study, we examined the effects of voluntary wheel running on the circadian corticosterone (Cort) rhythm as well as HPA axis responsiveness to, and recovery from, restraint stress. Male Sprague-Dawley rats were divided into exercise (E) and sedentary (S) groups, with E rats having 24-h access to running wheels for 5 wk. Circadian plasma Cort levels were measured at the end of each week, except for week 5 when rats were exposed to 20 min of restraint stress, followed by 95 min of recovery. Measurements of glucocorticoid receptor content in the hippocampus and anterior pituitary were performed using Western blotting at the termination of the restraint protocol. In week 1, circadian Cort levels were twofold higher in E compared with S animals, but the levels progressively decreased in the E group throughout the training protocol to reach similar values observed in S by week 4. During restraint stress and recovery, Cort values were similar between E and S, as was glucocorticoid receptor content in the hippocampus and pituitary gland after death. Compared with E, S animals had higher plasma ACTH levels during restraint. Taken together, these data indicate that 5 wk of wheel running are associated with normal circadian Cort activity and normal negative-feedback inhibition of the HPA axis, as well as with increased adrenal sensitivity to ACTH after restraint stress.

  19. Economics of site preparation and release treatments using herbicides in Central Georgia

    Treesearch

    Rodney L. Busby; James H. Miller; M. Boyd Edwards

    1998-01-01

    Abstract. Land expectation values (LEV) of site preparation and release treatments using herbicides in central Georgia are calculated and compared Loblolly pine growth and hardwood competition levels were measured at age 6 for the site preparation treatments and age 8 for the release treatments. These measurements were projected to final harvest...

  20. USDA National Nutrient Database for Standard Reference, Release 25

    USDA-ARS?s Scientific Manuscript database

    The USDA National Nutrient Database for Standard Reference, Release 25(SR25)contains data for over 8,100 food items for up to 146 food components. It replaces the previous release, SR24, issued in September 2011. Data in SR25 supersede values in the printed handbooks and previous electronic releas...

  1. 77 FR 3324 - Release of Airport Property: Page Field, Fort Myers, FL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-23

    ... subject airport and the Federal Aviation Administration. The release of property will allow the Lee County.... The property is located in the southwest corner of airport property, north of South Road, in Lee... released of its federal obligations to sell the property at Fair Market Value to Lee County for municipal...

  2. Calculation of Tectonic Strain Release from an Explosion in a Three-Dimensional Stress Field

    NASA Astrophysics Data System (ADS)

    Stevens, J. L.; O'Brien, M. S.

    2012-12-01

    We have developed a 3D nonlinear finite element code designed for calculation of explosions in 3D heterogeneous media and have incorporated the capability to perform explosion calculations in a prestressed medium. The effect of tectonic prestress on explosion-generated surface waves has been discussed since the 1960's. In most of these studies tectonic release was described as superposition of a tectonic source modeled as a double couple, multipole or moment tensor, plus a point explosion source. The size of the tectonic source was determined by comparison with the observed Love waves and the Rayleigh wave radiation pattern. Day et al. (1987) first attempted to perform numerical modeling of tectonic release through an axisymmetric calculation of the explosion Piledriver. To the best of our knowledge no one has previously performed numerical calculations for an explosion in a three-dimensional stress field. Calculation of tectonic release depends on a realistic representation of the stress state in the earth. In general the vertical stress is equal to the overburden weight of the material above at any given point. The horizontal stresses may be larger or smaller than this value up to the point where failure due to frictional sliding relieves the stress. In our calculations, we use the normal overburden calculation to determine the vertical stress, and then modify the horizontal stresses to some fraction of the frictional limit. This is the initial stable state of the calculation prior to introduction of the explosion. Note that although the vertical stress is still equivalent to the overburden weight, the pressure is not, and it may be either increased or reduced by the tectonic stresses. Since material strength increases with pressure, this also can substantially affect the seismic source. In general, normal faulting regimes will amplify seismic signals, while reverse faulting regimes will decrease seismic signals; strike-slip regimes may do either. We performed a 3D calculation of the Shoal underground nuclear explosion including tectonic prestress. Shoal was a 12.5 kiloton nuclear explosion detonated near Fallon, Nevada. This event had strong heterogeneity in near field waveforms and is in a region under primarily extensional tectonic stress. There were three near-field shot level recording stations located in three directions each at about 590 meters from the shot. Including prestress consistent with the regional stress field causes variations in the calculated near-field waveforms similar to those observed in the Shoal data.

  3. Absence of growth hormone (GH) secretion after the administration of either GH-releasing hormone (GHRH), GH-releasing peptide (GHRP-6), or GHRH plus GHRP-6 in children with neonatal pituitary stalk transection.

    PubMed

    Pombo, M; Barreiro, J; Peñalva, A; Peino, R; Dieguez, C; Casanueva, F F

    1995-11-01

    GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown, but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action occurs when both compounds are administered together. To explain such a synergistic effect, it has been postulated, but not proven, that GHRP-6 acts through a double mechanism, with actions exerted at the pituitary and the hypothalamic level. On the other hand, patients with the syndrome of GH deficiency due to perinatal pituitary stalk transection have any hypothalamic factor nonoperandi. The aim of the present study was 3-fold: 1) to further understand how relevant, if at all, the hypothalamic action of GHRP-6 is for GH regulation; 2) to evaluate whether GHRP-6 plus GHRH could be a suitable diagnostic tool in children with pituitary stalk transection; and 3) to compare these results with similar published studies performed in patients with hypothalamo-pituitary disconnection, who developed the disease as adults. Seven patients with GH deficiency and different degrees of panhypopituitarism due to perinatal pituitary stalk transection and 7 age- and sex-matched normal controls were studied. The subjects underwent 3 different tests on separate occasions, being challenged with GHRH (1 microgram/kg, iv), GHRP-6 (1 microgram/kg, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; micrograms per L/90 min). In normal subjects, GH secretion was 1029 +/- 202 after GHRH treatment, 1221 +/- 345 after GHRP-6, and 3542 +/- 650 after GHRH plus GHRP-6; the latter value was significantly (P < 0.05) higher than the secretion elicited by GHRH or GHRP-6 alone. In the group of patients with perinatal pituitary stalk transection, the level of GH after GHRH treatment was 116 +/- 22 and was even more reduced (P < 0.05) after GHRP-6 treatment (37 +/- 8). After GHRH plus GHRP-6, GH secretion in those patients was 177 +/- 27, significantly higher (P < 0.05) than the secretion induced by either GHRH or GHRP-6 alone. Individually examined, none of the patients tested with the most potent stimulus known to date (GHRH plus GHRP-6) exhibited GH secretion greater than 5 micrograms/L.(ABSTRACT TRUNCATED AT 400 WORDS)

  4. Using reference values to define disease based on the lower limit of normal biased the population attributable fraction, but not the population excess risk: the example of chronic airflow obstruction.

    PubMed

    Burney, Peter; Minelli, Cosetta

    2018-01-01

    The impact of disease on population health is most commonly estimated by the population attributable fraction (PAF), or less commonly by the excess risk, an alternative measure that estimates the absolute risk of disease in the population that can be ascribed to the exposure. Using chronic airflow obstruction as an example, we examined the impact on these estimates of defining disease based on different "normal" values. We estimated PAF and the excess risk in scenarios in which the true rate of disease was 10% in the exposed and 5% in the unexposed, and where either 50% or 20% of the population was exposed. Disease definition was based on a "lower limit of normal", using the 5th, 1st and 0.2nd centile of values in a "normal" population as thresholds to define normality. Where normality is defined by centiles of values in a "normal" population, PAF is strongly influenced by which centile is selected to define normality. This is not true for the population excess risk. Care should be taken when interpreting estimates of PAF when disease is defined from a centile of a normal population. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Measurements of normal joint angles by goniometry in calves.

    PubMed

    Sengöz Şirin, O; Timuçin Celik, M; Ozmen, A; Avki, S

    2014-01-01

    The aim of this study was to establish normal reference values of the forelimb and hindlimb joint angles in normal Holstein calves. Thirty clinically normal Holstein calves that were free of any detectable musculoskeletal abnormalities were included in the study. A standard transparent plastic goniometer was used to measure maximum flexion, maximum extension, and range-of-motion of the shoulder, elbow, carpal, hip, stifle, and tarsal joints. The goniometric measurements were done on awake calves that were positioned in lateral recumbency. The goniometric values were measured and recorded by two independent investigators. As a result of the study it was concluded that goniometric values obtained from awake calves in lateral recumbency were found to be highly consistent and accurate between investigators (p <0.05). The data of this study acquired objective and useful information on the normal forelimb and hindlimb joint angles in normal Holstein calves. Further studies can be done to predict detailed goniometric values from different diseases and compare them.

  6. Transient elastographic evaluation in adult subjects without overt liver disease: influence of alanine aminotransferase levels.

    PubMed

    Kumar, Manoj; Sharma, Praveen; Garg, Hitendra; Kumar, Ramesh; Bhatia, Vikram; Sarin, Shiv K

    2011-08-01

      Studies on normal values of liver stiffness (LS) in subjects at "low risk" for liver disease are scant. The aim of the present study was to assess liver stiffness values in the subjects without overt liver disease with normal alanine aminotransferases (ALT) and to determine potential factors, which may influence these values with special reference to newly suggested updated upper limits of normal for ALT.   Liver stiffness measurements were performed in 445 subjects without overt liver disease (mean age, 41.1±13.6; male, 73.5%) and normal liver enzymes.   Mean LS value was 5.10±1.19kPa. LS values were higher in men than in women (5.18±1.67 vs 4.86±1.24kPa, respectively, P=0.008); in subjects with higher body mass index (BMI) category (Normal, overweight and obese subjects; 4.10±0.75, 5.08±0.66, and 6.05±1.28kPa, respectively; P<0.001); in subjects with metabolic syndrome than in those without (5.63±1.37 vs 5.01±1.14kPa, P=0.001); and in subjects with ALT levels more than updated limits of normal compared to subjects with ALT levels less than updated limits of normal (5.68±1.21 vs 4.77±1.05kPa, P<0.001). On multiple linear regression, BMI and ALT was found to be significant predictor of LS.   Liver stiffness values in subjects without overt liver disease with normal ALT are influenced by BMI and ALT levels. Subjects with ALT levels less than updated limits of normal have lower LS values as compared to those with higher levels. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  7. Predicting Air Quality at First Ingress into Vehicles Visiting the International Space Station.

    PubMed

    Romoser, Amelia A; Scully, Robert R; Limero, Thomas F; De Vera, Vanessa; Cheng, Patti F; Hand, Jennifer J; James, John T; Ryder, Valerie E

    2017-02-01

    NASA regularly performs ground-based offgas tests (OGTs), which allow prediction of accumulated volatile pollutant concentrations at first entry on orbit, on whole modules and vehicles scheduled to connect to the International Space Station (ISS). These data guide crew safety operations and allow for estimation of ISS air revitalization systems impact from additional pollutant load. Since volatiles released from vehicle, module, and payload materials can affect crew health and performance, prediction of first ingress air quality is important. To assess whether toxicological risk is typically over or underpredicted, OGT and first ingress samples from 10 vehicles and modules were compared. Samples were analyzed by gas chromatography and gas chromatography-mass spectrometry. The rate of pollutant accumulation was extrapolated over time. Ratios of analytical values and Spacecraft Maximum Allowable Concentrations were used to predict total toxicity values (T-values) at first entry. Results were also compared by compound. Frequently overpredicted was 2-butanone (9/10), whereas propanal (6/10) and ethanol (8/10) were typically underpredicted, but T-values were not substantially affected. Ingress sample collection delay (estimated by octafluoropropane introduced from ISS atmosphere) and T-value prediction accuracy correlated well (R2 = 0.9008), highlighting the importance of immediate air sample collection and accounting for ISS air dilution. Importantly, T-value predictions were conservative 70% of the time. Results also suggest that T-values can be normalized to octafluoropropane levels to adjust for ISS air dilution at first ingress. Finally, OGT and ingress sampling has allowed small leaks in vehicle fluid systems to be recognized and addressed.Romoser AA, Scully RR, Limero TF, De Vera V, Cheng PF, Hand JJ, James JT, Ryder VE. Predicting air quality at first ingress into vehicles visiting the International Space Station. Aerosp Med Hum Perform. 2017; 88(2):104-113.

  8. Isotopic evidence for organic matter oxidation by manganese reduction in the formation of stratiform manganese carbonate ore

    USGS Publications Warehouse

    Okita, P.M.; Maynard, J.B.; Spiker, E. C.; Force, E.R.

    1988-01-01

    Unlike other marine-sedimentary manganese ore deposits, which are largely composed of manganese oxides, the primary ore at Molango (Hidalgo State, Mexico) is exclusively manganese carbonate (rhodochrosite, Mn-calcite, kutnahorite). Stable isotope studies of the carbonates from Molango provide critical new information relevant to the controversy over syngenetic and diagenetic models of stratiform manganese deposit formation. Negative ??13C values for carbonates from mineralized zones at Molango are strongly correlated with manganese content both on a whole rock scale and by mineral species. Whole rock ??13C data fall into three groups: high-grade ore = -16.4 to -11.5%.; manganese-rich, sub-ore-grade = -5.2 to 0%.; and unmineralized carbonates = 0 to +2.5%. (PDB). ??18O data show considerable overlap in values among the three groups: +4.8 to -2.8, -5.4 to -0.3%., and -7.4 to +6.2 (PDB), respectively. Isotopic data for individual co-existing minerals suggest a similar separation of ??13C values: ??13C values from calcite range from -1.1 to +0.7%. (PDB), whereas values from rhodochrosite are very negative, -12.9 to -5.5%., and values from kutnahorite or Mn-calcite are intermediate between calcite and rhodochrosite. 13C data are interpreted to indicate that calcite (i.e. unmineralized carbonate) formed from a normal marine carbon reservoir. However, 13C data for the manganese-bearing carbonates suggest a mixed seawater and organic source of carbon. The presence of only trace amounts of pyrite suggests sulfate reduction may have played a minor part in oxidizing organic matter. It is possible that manganese reduction was the predominant reaction that oxidized organic matter and that it released organic-derived CO2 to produce negative ??13C values and manganese carbonate mineralization. ?? 1988.

  9. ICP-MS measurement of diffusion coefficients of Cs in NBG-18 graphite

    NASA Astrophysics Data System (ADS)

    Carter, L. M.; Brockman, J. D.; Robertson, J. D.; Loyalka, S. K.

    2015-11-01

    Graphite is used in the HGTR/VHTR as moderator and it also functions as a barrier to fission product release. Therefore, an elucidation of transport of fission products in reactor-grade graphite is required. We have measured diffusion coefficients of Cs in graphite NBG-18 using the release method, wherein we infused spheres of NBG-18 with Cs and measured the release rates in the temperature range of 1090-1395 K. We have obtained: These seem to be the first reported values of Cs diffusion coefficients in NBG-18. The values are lower than those reported for other graphites in the literature.

  10. Conditions affecting the release of phosphorus from surface lake sediments.

    PubMed

    Christophoridis, Christophoros; Fytianos, Konstantinos

    2006-01-01

    Laboratory studies were conducted to determine the effect of pH and redox conditions, as well as the effect of Fe, Mn, Ca, Al, and organic matter, on the release of ortho-phosphates in lake sediments taken from Lakes Koronia and Volvi (Northern Greece). Results were evaluated in combination with experiments to determine P fractionation in the sediment. The study revealed the major effect of redox potential and pH on the release of P from lake sediments. Both lakes showed increased release rates under reductive conditions and high pH values. The fractionation experiments revealed increased mobility of the reductive P fraction as well as of the NaOH-P fraction, indicating participation of both fractions in the overall release of sediment-bound P, depending on the prevailing environmental conditions. The results were assessed in combination with the release patterns of Fe, Mn, Ca, Al, and organic matter, enabling the identification of more specific processes of P release for each lake. The basic release patterns included the redox induced reductive dissolution of P-bearing metal oxides and the competitive exchange of phosphate anions with OH- at high pH values. The formation of an oxidized surface microlayer under oxic conditions acted as a protective film, preventing further P release from the sediments of Lake Volvi, while sediments from Lake Koronia exhibited a continuous and increased tendency to release P under various physicochemical conditions, acting as a constant source of internal P loading.

  11. Salt-Finger Convection in a Stratified Fluid Layer Induced by Thermal and Solutal Capillary Motion

    NASA Technical Reports Server (NTRS)

    Chen, Chuan F.; Chan, Cho Lik

    1996-01-01

    Salt-finger convection in a double-diffusive system is a motion driven by the release of gravitational potential due to different diffusion rates. Normally, when the gravitational field is reduced, salt-finger convection together with other convective motions driven by buoyancy forces will be rapidly suppressed. However, because the destabilizing effect of the concentration gradient is amplified by the Lewis number, with values varying from 10(exp 2) for aqueous salt solutions to 10 (exp 4) for liquid metals, salt-finger convection may be generated at much reduced gravity levels. In the microgravity environment, the surface tension gradient assumes a dominant role in causing fluid motion. In this paper, we report on some experimental results showing the generation of salt-finger convection due to capillary motio on the surface of a stratified fluid layer. A numerical simulation is presented to show the cause of salt-finger convection.

  12. An extended superhot solar flare X-ray source

    NASA Technical Reports Server (NTRS)

    Hudson, H. S.; Ohki, K. I.; Tsuneta, S.

    1985-01-01

    A superhot hard X-ray source in a solar flare occulted by the solar limb was identified. Its hard X-ray image was found to show great horizontal extent but little vertical extent. An H alpha brightening at the same limb position about an hour later suggests a multi-component loop prominence system, so that it appears that a superhot source can evolve in the same manner as a normal solar soft X-ray source. The assignment of plausiable values to physical parameters in the source suggests (from the simplest form of classical thermal-conduction theory) that either new physics will be required to suppress conduction, or else that gradual energy release well after the impulsive phase of the flare must occur. In this respect too, the superhot source appears to resemble ordinary soft X-ray sources, except of course that its temperature is higher.

  13. Understanding the Changes to Biomass Surface Characteristics after Ammonia and Organosolv Pretreatments by Using Time-of-Flight Secondary-Ion Mass Spectrometry (TOF-SIMS)

    DOE PAGES

    Tolbert, Allison K.; Yoo, Chang Geun; Ragauskas, Arthur J.

    2017-03-20

    Surface characteristic changes to poplar after ammonia and organosolv pretreatments were investigated by means of time-of-flight secondary-ion mass spectrometry (TOF-SIMS) analysis. Whereas normalized total polysaccharides and lignin contents on the surface differed from bulk chemical compositions, the surface cellulose ions detected by TOF-SIMS showed the same value trend as the cellulose content in the biomass. In addition, the lignin syringyl/guaiacyl ratio according to TOF-SIMS results showed the same trend as the ratio measured by means of NMR spectroscopic analysis, even though the ratio scales for each method were different. A similar correlation was determined between the surface cellulose and glucosemore » release after enzymatic hydrolysis. Lastly, these results demonstrate that surface characterization using TOF-SIMS can provide important information about the effects of pretreatment on biomass properties and its hydrolysis.« less

  14. New evidence for chemical fractionation of radioactive xenon precursors in fission chains

    PubMed Central

    Meshik, A. P.; Pravdivtseva, O. V.; Hohenberg, C. M.

    2017-01-01

    Mass-spectrometric analyses of Xe released from acid-treated U ore reveal that apparent Xe fission yields significantly deviate from the normal values. The anomalous Xe structure is attributed to chemically fractionated fission (CFF), previously observed only in materials experienced neutron bursts. The least retentive CFF-Xe isotopes, 136Xe and 134Xe, typically escape in 2:1 proportion. Xe retained in the sample is complimentarily depleted in these isotopes. This nucleochemical process allows understanding of unexplained Xe isotopic structures in several geophysical environments, which include well gasses, ancient anorthosite, some mantle rocks, as well as terrestrial atmosphere. CFF is likely responsible for the isotopic difference in Xe in the Earth’s and Martian atmospheres and it is capable of explaining the relationship between two major solar system Xe carriers: the Sun and phase-Q, found in meteorites. PMID:29177205

  15. Noninvasive in vivo optical characterization of blood flow and oxygen consumption in the superficial plexus of skin

    NASA Astrophysics Data System (ADS)

    Liasi, Faezeh Talebi; Samatham, Ravikant; Jacques, Steven L.

    2017-11-01

    Assessing the metabolic activity of a tissue, whether normal, damaged, aged, or pathologic, is useful for diagnosis and evaluating the effects of drugs. This report describes a handheld optical fiber probe that contacts the skin, applies pressure to blanch the superficial vascular plexus of the skin, then releases the pressure to allow refill of the plexus. The optical probe uses white light spectroscopy to record the time dynamics of blanching and refilling. The magnitude and dynamics of changes in blood content and hemoglobin oxygen saturation yield an estimate of the oxygen consumption rate (OCR) in units of attomoles per cell per second. The average value of OCR on nine forearm sites on five subjects was 10±5 (amol/cell/s). This low-cost, portable, rapid, noninvasive optical probe can characterize the OCR of a skin site to assess the metabolic activity of the epidermis or a superficial lesion.

  16. Understanding the Changes to Biomass Surface Characteristics after Ammonia and Organosolv Pretreatments by Using Time-of-Flight Secondary-Ion Mass Spectrometry (TOF-SIMS)

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

    Tolbert, Allison K.; Yoo, Chang Geun; Ragauskas, Arthur J.

    Surface characteristic changes to poplar after ammonia and organosolv pretreatments were investigated by means of time-of-flight secondary-ion mass spectrometry (TOF-SIMS) analysis. Whereas normalized total polysaccharides and lignin contents on the surface differed from bulk chemical compositions, the surface cellulose ions detected by TOF-SIMS showed the same value trend as the cellulose content in the biomass. In addition, the lignin syringyl/guaiacyl ratio according to TOF-SIMS results showed the same trend as the ratio measured by means of NMR spectroscopic analysis, even though the ratio scales for each method were different. A similar correlation was determined between the surface cellulose and glucosemore » release after enzymatic hydrolysis. Lastly, these results demonstrate that surface characterization using TOF-SIMS can provide important information about the effects of pretreatment on biomass properties and its hydrolysis.« less

  17. Characteristic Study of Some Different Kinds of Coal Particles Combustion with Online TG-MS-FTIR

    NASA Astrophysics Data System (ADS)

    Pan, Guanfu

    2018-01-01

    Four kinds of pulverized coal samples from China and Indonesia were studied by thermogravimetry coupled with mass spectrometry and fourier transform infrared spectroscopy (TG-MS-FTIR). The thermal behaviors and gaseous emissions of these coals were analyzed in this work. The results indicate that the relative lower values of H/C ratios, which normally represent the degree of aromatization and ring condensation in coal samples, could lead to the relative more intense thermal reaction. The time-evolved profiles of some typical gas products (i.e., CO, SO2, CH4, NO, NO2, NH3 and etc.) were provided by TG-MS-FTIR, and their variations are different. For all the samples, the releases of SO2 and COS can be found at lower temperature than those of NO and CO. As the temperature increases, the possible conversion of NO2 and NH3 to NO is deduced in this work.

  18. A Statistical Selection Strategy for Normalization Procedures in LC-MS Proteomics Experiments through Dataset Dependent Ranking of Normalization Scaling Factors

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

    Webb-Robertson, Bobbie-Jo M.; Matzke, Melissa M.; Jacobs, Jon M.

    2011-12-01

    Quantification of LC-MS peak intensities assigned during peptide identification in a typical comparative proteomics experiment will deviate from run-to-run of the instrument due to both technical and biological variation. Thus, normalization of peak intensities across a LC-MS proteomics dataset is a fundamental step in pre-processing. However, the downstream analysis of LC-MS proteomics data can be dramatically affected by the normalization method selected . Current normalization procedures for LC-MS proteomics data are presented in the context of normalization values derived from subsets of the full collection of identified peptides. The distribution of these normalization values is unknown a priori. If theymore » are not independent from the biological factors associated with the experiment the normalization process can introduce bias into the data, which will affect downstream statistical biomarker discovery. We present a novel approach to evaluate normalization strategies, where a normalization strategy includes the peptide selection component associated with the derivation of normalization values. Our approach evaluates the effect of normalization on the between-group variance structure in order to identify candidate normalization strategies that improve the structure of the data without introducing bias into the normalized peak intensities.« less

  19. A photoelectrochemical platform for the capture and release of rare single cells.

    PubMed

    Parker, Stephen G; Yang, Ying; Ciampi, Simone; Gupta, Bakul; Kimpton, Kathleen; Mansfeld, Friederike M; Kavallaris, Maria; Gaus, Katharina; Gooding, J Justin

    2018-06-12

    For many normal and aberrant cell behaviours, it is important to understand the origin of cellular heterogeneity. Although powerful methods for studying cell heterogeneity have emerged, they are more suitable for common rather than rare cells. Exploring the heterogeneity of rare single cells is challenging because these rare cells must be first pre-concentrated and undergo analysis prior to classification and expansion. Here, a versatile capture & release platform consisting of an antibody-modified and electrochemically cleavable semiconducting silicon surface for release of individual cells of interest is presented. The captured cells can be interrogated microscopically and tested for drug responsiveness prior to release and recovery. The capture & release strategy was applied to identify rare tumour cells from whole blood, monitor the uptake of, and response to, doxorubicin and subsequently select cells for single-cell gene expression based on their response to the doxorubicin.

  20. Plasma peptide YY (PYY) in dumping syndrome.

    PubMed

    Adrian, T E; Long, R G; Fuessl, H S; Bloom, S R

    1985-12-01

    The newly isolated hormonal peptide PYY is mainly localized to endocrine cells of the lower intestinal mucosa. The release of PYY by oral glucose was studied in six patients with the dumping syndrome to ascertain the effect of this condition on PYY release. Plasma PYY concentrations were greatly increased following oral glucose in patients with the dumping syndrome compared with healthy controls. In a separate series of experiments, the effect of somatostatin infusion on the PYY release by glucose in these patients was investigated. The release of PYY was completely blocked by infusion of somatostatin, and its release from the bowel in normal subjects may therefore be modulated by local somatostatin in the gut. PYY has been shown to inhibit gastric acid secretion and emptying, at plasma concentrations similar to those seen after glucose, in patients with the dumping syndrome. PYY may therefore be a factor involved in the pathophysiological changes associated with this condition.

  1. Uranium release from different size fractions of sediments in Hanford 300 area, Washington, USA.

    PubMed

    Du, Jiangkun; Bao, Jianguo; Hu, Qinhong; Ewing, Robert P

    2012-05-01

    Stirred-flow cell tests were carried out to investigate uranium (U) release from different size fractions of sediments from the U.S. Department of Energy's Hanford 300 Area in Washington, USA. Results show that the measured concentration of U release varies with different size fractions, with the fine-grained mass fractions (<75 μm, 75-500 μm, and 500-2000 μm) being the main U carriers. However, because the sediment is mainly composed of gravel (2000-8000 μm) materials, the gravel fraction is a non-negligible U pool. Our elution experiments give a value of 8.7% of the total U being in the gravel fraction, significantly reducing the current uncertainty in evaluating U inventory. A log-log plot of released U concentration vs. elution volume (i.e., elution time) shows a power-law relationship for all size fractions, with identical exponents for the three fine size fractions (-0.875). For the <2000 μm mass fraction, comparing our eluted U values with reported total U concentrations, we estimate that a lower bound value 8.6% of the total uranium is labile. This compares well with the previously published value of 11.8% labile U after extraction with a dilute extractant for three weeks. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. IRAS sky survey atlas: Explanatory supplement

    NASA Technical Reports Server (NTRS)

    Wheelock, S. L.; Gautier, T. N.; Chillemi, J.; Kester, D.; Mccallon, H.; Oken, C.; White, J.; Gregorich, D.; Boulanger, F.; Good, J.

    1994-01-01

    This Explanatory Supplement accompanies the IRAS Sky Survey Atlas (ISSA) and the ISSA Reject Set. The first ISSA release in 1991 covers completely the high ecliptic latitude sky, absolute value of beta is greater than 50 deg, with some coverage down to the absolute value of beta approx. equal to 40 deg. The second ISSA release in 1992 covers ecliptic latitudes of 50 deg greater than the absolute value of beta greater than 20 deg, with some coverage down to the absolute value of beta approx. equal to 13 deg. The remaining fields covering latitudes within 20 deg of the ecliptic plane are of reduced quality compared to the rest of the ISSA fields and therefore are released as a separate IPAC product, the ISSA Reject Set. The reduced quality is due to contamination by zodiacal emission residuals. Special care should be taken when using the ISSA Reject images. In addition to information on the ISSA images, some information is provided in this Explanatory Supplement on the IRAS Zodiacal History File (ZOHF), Version 3.0, which was described in the December 1988 release memo. The data described in this Supplement are available at the National Space Science Data Center (NSSDC) at the Goddard Space Flight Center. The interested reader is referred to the NSSDC for access to the IRAS Sky Survey Atlas (ISSA).

  3. A Conservative Inverse Normal Test Procedure for Combining P-Values in Integrative Research.

    ERIC Educational Resources Information Center

    Saner, Hilary

    1994-01-01

    The use of p-values in combining results of studies often involves studies that are potentially aberrant. This paper proposes a combined test that permits trimming some of the extreme p-values. The trimmed statistic is based on an inverse cumulative normal transformation of the ordered p-values. (SLD)

  4. Stress- and sequence-dependent release into the culture medium of HIV-1 Nef produced in Saccharomyces cerevisiae.

    PubMed

    Macreadie, I G; Castelli, L A; Lucantoni, A; Azad, A A

    1995-09-11

    We have produced human immunodeficiency virus type 1 (HIV-1) Nef (a myristylated 206-amino-acid protein) in Saccharomyces cerevisaie and shown that, while Nef is normally found as a predominantly intracellular protein, amounts up to 40 micrograms/ml of Nef are also released into the extracellular medium during stress. By electrophoretic (SDS-PAGE) analysis the extracellular Nef is indistinguishable from intracellular Nef. Conditions of stress that lead to the release of Nef include elevated levels of copper or magnesium ions or growth at elevated temperatures. This release appears to be dependent upon the N-terminal sequences of Nef, including the presence of a myristylation site. Our observations concerning Nef release in yeast suggest new ways in which the behaviour of Nef should be examined in order to gain further insights into the development of AIDS. If the release of Nef is important in the development of AIDS, our work reveals that Nef-associated symptoms may be reduced or delayed by reducing stresses, such as fevers.

  5. A transient dopamine signal encodes subjective value and causally influences demand in an economic context

    PubMed Central

    Schelp, Scott A.; Pultorak, Katherine J.; Rakowski, Dylan R.; Gomez, Devan M.; Krzystyniak, Gregory; Das, Raibatak; Oleson, Erik B.

    2017-01-01

    The mesolimbic dopamine system is strongly implicated in motivational processes. Currently accepted theories suggest that transient mesolimbic dopamine release events energize reward seeking and encode reward value. During the pursuit of reward, critical associations are formed between the reward and cues that predict its availability. Conditioned by these experiences, dopamine neurons begin to fire upon the earliest presentation of a cue, and again at the receipt of reward. The resulting dopamine concentration scales proportionally to the value of the reward. In this study, we used a behavioral economics approach to quantify how transient dopamine release events scale with price and causally alter price sensitivity. We presented sucrose to rats across a range of prices and modeled the resulting demand curves to estimate price sensitivity. Using fast-scan cyclic voltammetry, we determined that the concentration of accumbal dopamine time-locked to cue presentation decreased with price. These data confirm and extend the notion that dopamine release events originating in the ventral tegmental area encode subjective value. Using optogenetics to augment dopamine concentration, we found that enhancing dopamine release at cue made demand more sensitive to price and decreased dopamine concentration at reward delivery. From these observations, we infer that value is decreased because of a negative reward prediction error (i.e., the animal receives less than expected). Conversely, enhancing dopamine at reward made demand less sensitive to price. We attribute this finding to a positive reward prediction error, whereby the animal perceives they received a better value than anticipated. PMID:29109253

  6. Normalization is a general neural mechanism for context-dependent decision making

    PubMed Central

    Louie, Kenway; Khaw, Mel W.; Glimcher, Paul W.

    2013-01-01

    Understanding the neural code is critical to linking brain and behavior. In sensory systems, divisive normalization seems to be a canonical neural computation, observed in areas ranging from retina to cortex and mediating processes including contrast adaptation, surround suppression, visual attention, and multisensory integration. Recent electrophysiological studies have extended these insights beyond the sensory domain, demonstrating an analogous algorithm for the value signals that guide decision making, but the effects of normalization on choice behavior are unknown. Here, we show that choice models using normalization generate significant (and classically irrational) choice phenomena driven by either the value or number of alternative options. In value-guided choice experiments, both monkey and human choosers show novel context-dependent behavior consistent with normalization. These findings suggest that the neural mechanism of value coding critically influences stochastic choice behavior and provide a generalizable quantitative framework for examining context effects in decision making. PMID:23530203

  7. The role of luminal Ca2+ in the generation of Ca2+ waves in rat ventricular myocytes

    PubMed Central

    Lukyanenko, Valeriy; Subramanian, Saisunder; Györke, Inna; Wiesner, Theodore F; Györke, Sandor

    1999-01-01

    We used confocal Ca2+ imaging and fluo-3 to investigate the transition of localized Ca2+ releases induced by focal caffeine stimulation into propagating Ca2+ waves in isolated rat ventricular myocytes. Self-sustaining Ca2+ waves could be initiated when the cellular Ca2+ load was increased by elevating the extracellular [Ca2+] ([Ca2+]o) and they could also be initiated at normal Ca2+ loads when the sensitivity of the release sites to cytosolic Ca2+ was enhanced by low doses of caffeine. When we prevented the accumulation of extra Ca2+ in the luminal compartment of the sarcoplasmic reticulum (SR) with thapsigargin, focal caffeine pulses failed to trigger self-sustaining Ca2+ waves on elevation of [Ca2+]o. Inhibition of SR Ca2+ uptake by thapsigargin in cells already preloaded with Ca2+ above normal levels did not prevent local Ca2+ elevations from triggering propagating waves. Moreover, wave velocity increased by 20 %. Tetracaine (0·75 mM) caused transient complete inhibition of both local and propagating Ca2+ signals, followed by full recovery of the responses due to increased SR Ca2+ accumulation. Computer simulations using a numerical model with spatially distinct Ca2+ release sites suggested that increased amounts of releasable Ca2+ might not be sufficient to generate self-sustaining Ca2+ waves under conditions of Ca2+ overload unless the threshold of release site Ca2+ activation was set at relatively low levels (< 1·5 μM). We conclude that the potentiation of SR Ca2+ release channels by luminal Ca2+ is an important factor in Ca2+ wave generation. Wave propagation does not require the translocation of Ca2+ from the spreading wave front into the SR. Instead, it relies on luminal Ca2+ sensitizing Ca2+ release channels to cytosolic Ca2+. PMID:10373699

  8. Aspartic acid

    MedlinePlus

    ... we eat. Aspartic acid is also called asparaginic acid. Aspartic acid helps every cell in the body work. It ... release Normal nervous system function Plant sources of aspartic acid include: avocado, asparagus, and molasses. Animal sources of ...

  9. Increased Antibiotic Release from a Bone Cement Containing Bacterial Cellulose

    PubMed Central

    Nakai, Takahisa; Enomoto, Koichi; Uchio, Yuji; Yoshino, Katsumi

    2010-01-01

    Background Major disadvantages of antibiotic bone cements include limited drug release and reduced strength resulting from the addition of high doses of antibiotics. Bacterial cellulose, a three-dimensional hydrophilic mesh, may retain antibiotics and release them gradually. We hypothesized that the addition of cellulose to antibiotic bone cement would improve mechanical strength and antibiotic release. Questions/purposes We therefore examined the mechanical strength and antibiotic release of cellulose antibiotic cement. Methods A high dose of antibiotics (5 g per 40 g cement powder) was incorporated into bacterial cellulose and then mixed with bone cement. We compared the compression strength, fracture toughness, fatigue life, and elution kinetics of this formulation with those of plain cement and a traditional antibiotic cement. Results The average values for compression strength, fracture toughness, and fatigue life of the cellulose antibiotic cement were 97%, 97%, and 78% of the values obtained for plain cement, respectively. The corresponding values for the traditional antibiotic cement were 79%, 82%, and 17%, respectively. The cumulative elution over 35 days was 129% greater from the cellulose antibiotic cement than from the traditional antibiotic cement. Conclusions With a high dose of antibiotics, incorporating cellulose into the bone cement prevented compression and fracture fragility, improved fatigue life, and increased antibiotic elution. Clinical Relevance Antibiotic cements containing cellulose may have applications in clinical situations that require high levels of antibiotic release and preservation of the mechanical properties of the cement. PMID:20945120

  10. A role for the anandamide membrane transporter in TRPV1-mediated neurosecretion from trigeminal sensory neurons

    PubMed Central

    Price, Theodore J.; Patwardhan, Amol M.; Flores, Christopher M.; Hargreaves, Kenneth M.

    2007-01-01

    Many n-acylethanolamines utilize the anandamide membrane transporter (AMT) to gain facilitated access to the intracellular compartment, hence, we hypothesized that this mechanism might be important for anandamide (AEA)- and N-arachidonoyl-dopamine (NADA)-evoked CGRP release from cultured trigeminal ganglion (TG) neurons. Using [14C]AEA we demonstrated that TG neurons transported AEA in a FAAH- and AMT-inhibitable fashion. Although TRPV1-positive TG neurons were found to express fatty acid amide hydrolase, the application of FAAH inhibitors had no effect on AEA-evoked CGRP release. In contrast, application of the AMT inhibitors OMDM-2 or VDM-11 significantly reduced the potency and efficacy of AEA-, NADA- and capsaicin-evoked CGRP release. Moreover OMDM-2 (IC50 values ranging from 6.4–9.6 μM) and VDM-11 (IC50 values ranging from 5.3–11 μM) inhibited CGRP release evoked by EC80 concentrations of AEA, NADA and CAP and these values were consistent with IC50s obtained for inhibition of uptake. OMDM-2 had no effect on CGRP release per se while VDM-11 evoked CGRP release on its own (EC50 ~35 μM) in a CPZ-insensitive, but ruthenium red (RR)-sensitive fashion. This is the first demonstration that TG sensory neurons possess an AMT-like mechanism suggesting that this mechanism is important for the pharmacological action of AEA and NADA at native TRPV1 channels. PMID:15992578

  11. The effect of anions on bound acetylcholine in frog sartorius muscle.

    PubMed Central

    Ceccarelli, B; Molenaar, P C; Oen, B S; Polak, R L; Torri-Tarelli, F; van Kempen, G T

    1989-01-01

    1. Frog sartorius muscles were treated with an irreversible cholinesterase inhibitor and then incubated in isotonic potassium propionate solution (isotonic KPr). Total and bound, presumably vesicular, acetylcholine (ACh) in the tissue and ACh in the medium were assayed by mass fragmentography, miniature end-plate potentials (MEPPs) were recorded and the end-plates were investigated by electron microscopy. 2. Incubation in isotonic KPr for 30 min stimulated ACh release and concomitantly decreased total and bound ACh. Nerve stimulation for 30 min by trains of impulses (0.1 s trains of 100 Hz, 1 train s-1) in normal-potassium propionate-containing solution had the same effects. 3. When the tissue was incubated in normal-K+ Ringer solution for 3 h, following chemical or electric stimulation, bound ACh recovered to about 75% of the initial value, provided that Cl- ions were present in the medium. In the presence of propionate instead of Cl- ions almost no recovery of bound ACh took place. There was also recovery of bound ACh in the presence of either NO3- or gluconate ions. In NO3- it was the same as in Cl-, but in gluconate it was less than found in Cl- -containing medium. 4. Recovery of total ACh, in contrast to bound ACh, took place even in the presence of propionate ions, showing that extracellular Cl- is not required for the synthesis of ACh. 5. In terminals recovered in normal Ringer solution, many synaptic vesicles were found, but terminals 'recovered' in propionate solution were depleted of vesicles. 6. From these and other results it is concluded that the recycling of synaptic vesicles normally requires the presence of extracellular chloride. Images Fig. 1 Fig. 2 PMID:2789283

  12. Validation of in vitro assays in three-dimensional human dermal constructs.

    PubMed

    Idrees, Ayesha; Chiono, Valeria; Ciardelli, Gianluca; Shah, Siegfried; Viebahn, Richard; Zhang, Xiang; Salber, Jochen

    2018-05-01

    Three-dimensional cell culture systems are urgently needed for cytocompatibility testing of biomaterials. This work aimed at the development of three-dimensional in vitro dermal skin models and their optimization for cytocompatibility evaluation. Initially "murine in vitro dermal construct" based on L929 cells was generated, leading to the development of "human in vitro dermal construct" consisting of normal human dermal fibroblasts in rat tail tendon collagen type I. To assess the viability of the cells, different assays CellTiter-Blue ® , RealTime-Glo ™ MT, and CellTiter-Glo ® (Promega) were evaluated to optimize the best-suited assay to the respective cell type and three-dimensional system. Z-stack imaging (Live/Dead and Phalloidin/DAPI-Promokine) was performed to visualize normal human dermal fibroblasts inside matrix revealing filopodia-like morphology and a uniform distribution of normal human dermal fibroblasts in matrix. CellTiter-Glo was found to be the optimal cell viability assay among those analyzed. CellTiter-Blue reagent affected the cell morphology of normal human dermal fibroblasts (unlike L929), suggesting an interference with cell biological activity, resulting in less reliable viability data. On the other hand, RealTime-Glo provided a linear signal only with a very low cell density, which made this assay unsuitable for this system. CellTiter-Glo adapted to three-dimensional dermal construct by optimizing the "shaking time" to enhance the reagent penetration and maximum adenosine triphosphate release, indicating 2.4 times higher viability value by shaking for 60 min than for 5 min. In addition, viability results showed that cells were viable inside the matrix. This model would be further advanced with more layers of skin to make a full thickness model.

  13. Plasma glycoprotein V levels in the general population: normal distribution, associated parameters and implications for clinical studies.

    PubMed

    Aleil, Boris; Meyer, Nicolas; Wolff, Valérie; Kientz, Daniel; Wiesel, Marie-Louise; Gachet, Christian; Cazenave, Jean-Pierre; Lanza, François

    2006-10-01

    Soluble glycoprotein V (sGPV) is a new plasma marker of thrombosis released from the platelet surface by thrombin. sGPV levels are increased in patients with atherothrombotic diseases, but the determinants of sGPV levels are unknown in the general population. Identification of these potential confounding factors is needed for correct design and analysis of clinical studies on cardiovascular diseases. The aim of this study was to determine the normal range of plasma values and the factors controlling sGPV levels in a population of normal individuals. Three hundred blood donors were recruited at the Etablissement Français du Sang-Alsace for the measurement of plasma levels of sGPV, platelet factor 4 (PF4), thrombin-antithrombin complexes (TAT) and D-dimers. The plasma level of sGPV was (median [interquartile range]) 27.5 [23.5-34.4] microg/l and displayed a Gaussian distribution. sGPV had a lower interindividual coefficient of variation (33%) than PF4 (176%), TAT (87%) or D-dimers (82%). sGPV levels were independent of age and sex but sensitive to red cell (r = 0.412; p < 0.0001) and platelet counts (r = 0.267; p = 0.001), total cholesterol (r = -0.313; p < 0.0001), food intake (r = 0.184; p = 0.0014) and smoking (r = -0.154; p = 0.039). Contrary to PF4 and TAT, sGPV did not differ between venous and arterial blood samples of 12 healthy individuals. Red cell and platelet counts, total cholesterol, current smoking and recent food intake are important determinants of sGPV levels and must be taken into account in clinical studies using sGPV as a thrombosis marker. Normal distribution of sGPV levels in the general population supports its use in clinical applications.

  14. The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly.

    PubMed

    Alster, D K; Bowers, C Y; Jaffe, C A; Ho, P J; Barkan, A L

    1993-09-01

    In patients with acromegaly, GH-producing pituitary tumors release GH in response to specific stimuli such as GH-releasing hormone (GHRH) and are also responsive to a variety of nonspecific stimuli, such as TRH or GnRH, and may exhibit paradoxical responses to glucose and dopamine. In healthy humans, the synthetic peptide GH-releasing peptide (GHRP) (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) releases GH by a putative mechanism of action that is independent of GHRH. How these tumors respond to GHRP is not well characterized. We studied the GH responses to GHRH, GHRP, and TRH stimulation in 11 patients with active acromegaly. The peak GH responses to GHRP and GHRH were not correlated (r = 0.57; P = 0.066). In contrast, the peak GH responses to GHRP and TRH were highly correlated (r = 0.95; P < 0.001). In conclusion, in patients with acromegaly, the GH response to GHRP is qualitatively normal and does not appear to depend on GHRH.

  15. Normalizing Catastrophe: An Educational Response

    ERIC Educational Resources Information Center

    Jickling, Bob

    2013-01-01

    Processes of normalizing assumptions and values have been the subjects of theoretical framing and critique for several decades now. Critique has often been tied to issues of environmental sustainability and social justice. Now, in an era of global warming, there is a rising concern that the results of normalizing of present values could be…

  16. New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

    PubMed

    Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

    1992-10-01

    The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

  17. A novel fibrinogen variant--Praha I: hypofibrinogenemia associated with gamma Gly351Ser substitution.

    PubMed

    Kotlín, Roman; Chytilová, Martina; Suttnar, Jirí; Salaj, Peter; Riedel, Tomás; Santrůcek, Jirí; Klener, Pavel; Dyr, Jan Evangelista

    2007-05-01

    A 25-yr-old man from Prague had abnormal bleeding after several surgical operations with low fibrinogen level and hypofibrinogenemia was suspected. The patient, 25 yr-old male had a low fibrinogen concentration as determined by the thrombin time and immunoturbidimetrical method. His 48-yr-old mother presented with normal coagulation tests, normal fibrinogen level and reported no history of bleeding. To identify the genetic mutation responsible for this hypofibrinogen, genomic DNA extracted from the blood was analyzed. Fibrin polymerization measurement, kinetics of fibrinopeptide release, fibrinogen clottability measurement, mass spectroscopy, and scanning electron microscopy were performed. DNA sequencing showed heterogeneous fibrinogen gammaG351S mutation in the propositus. The mutant chain was found not to be expressed to the circulation by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Scanning electron micrographs of the patient's fibrin clot as well as kinetics of fibrinopeptide release and fibrin polymerization were found to be normal. A case of hypofibrinogenemia gammaG351S was found by routine coagulation testing and was genetically identified.

  18. Improved Root Normal Size Distributions for Liquid Atomization

    DTIC Science & Technology

    2015-11-01

    Jackson, Primary Breakup of Round Aerated- Liquid Jets in Supersonic Crossflows, Atomization and Sprays, 16(6), 657-672, 2006 H. C. Simmons, The...Breakup in Liquid - Gas Mixing Layers, Atomization and Sprays, 1, 421-440, 1991 P.-K. Wu, L.-K. Tseng, and G. M. Faeth, Primary Breakup in Gas / Liquid ...Improved Root Normal Size Distributions for Liquid Atomization Distribution Statement A. Approved for public release; distribution is unlimited

  19. Characterization of 24-h cortisol release in obese and non-obese hyperandrogenic women.

    PubMed

    Miller, J E; Bray, M A; Faiman, C; Reyes, F I

    1994-12-01

    Excessive androgen output is a well-recognized feature of adrenocortical oversecretion in women with ovarian hyperandrogenism, or polycystic ovary disease (PCOD). However, evidence of a concomitant alteration of cortisol secretion is lacking even though obesity per se, a common clinical feature of PCOD, has been shown to be associated with cortisol oversecretion. To clarify whether a subtle alteration in cortisol secretion exists, a study of 24-h episodic cortisol release and post-prandial cortisol responses was undertaken in eight women with PCOD and eight normal women comprising equal numbers of obese and non-obese subjects. All four groups showed normal biphasic 24-h cortisol secretion profiles but cortisol pulse frequency was increased in the PCOD groups. Independently, both hyperandrogenism and obesity were associated with an accelerated cortisol clearance rate. These changes, together with normal or only slightly elevated 24-h cortisol integrated area under the curve, suggest an increased compensatory cortisol production in women with PCOD. Furthermore, subjects with PCOD and subjects with obesity showed different post-prandial cortisol responses to normal non-obese women. In conclusion, these subtle cortisol abnormalities may be a manifestation of altered central regulation of the hypothalamic-pituitary-adrenal axis and peripheral metabolic abnormalities, and may be linked to the pathophysiology of PCOD.

  20. Evaluation of Kurtosis into the product of two normally distributed variables

    NASA Astrophysics Data System (ADS)

    Oliveira, Amílcar; Oliveira, Teresa; Seijas-Macías, Antonio

    2016-06-01

    Kurtosis (κ) is any measure of the "peakedness" of a distribution of a real-valued random variable. We study the evolution of the Kurtosis for the product of two normally distributed variables. Product of two normal variables is a very common problem for some areas of study, like, physics, economics, psychology, … Normal variables have a constant value for kurtosis (κ = 3), independently of the value of the two parameters: mean and variance. In fact, the excess kurtosis is defined as κ- 3 and the Normal Distribution Kurtosis is zero. The product of two normally distributed variables is a function of the parameters of the two variables and the correlation between then, and the range for kurtosis is in [0, 6] for independent variables and in [0, 12] when correlation between then is allowed.

  1. Prevention of VOC releases from bridge painting operations.

    DOT National Transportation Integrated Search

    2007-06-01

    Bridge maintenance painting employs solvent-based coatings that generate volatile organic compounds (VOCs) that contribute to air-quality problems. Methods for capturing VOCs during normal Kentucky Transportation Cabinet (KYTC) maintenance painting o...

  2. Protection against ultraviolet A-induced oxidative damage in normal human epidermal keratinocytes under post-menopausal conditions by an ultraviolet A-activated caged-iron chelator: a pilot study.

    PubMed

    Pelle, Edward; Jian, Jinlong; Declercq, Lieve; Dong, Kelly; Yang, Qing; Pourzand, Charareh; Maes, Daniel; Pernodet, Nadine; Yarosh, Daniel B; Huang, Xi

    2011-10-01

    Human skin is constantly exposed to ultraviolet A (UVA), which can generate reactive oxygen species and cause iron release from ferritin, leading to oxidative damage in biomolecules. This is particularly true in post-menopausal skin due to an increase in iron as a result of menopause. As iron is generally released through desquamation, the skin becomes a main portal for the release of excess iron in this age group. In the present study, we examined a strategy for controlling UVA- and iron-induced oxidative stress in skin using a keratinocyte post-menopausal cellular model system. Keratinocytes that had been cultured under normal or high-iron, low-estrogen conditions were treated with (2-nitrophenyl) ethyl pyridoxal isonicotinoyl hydrazone (2-PNE-PIH). 2-PNE-PIH is a caged-iron chelator that does not normally bind iron but can be activated by UVA radiation to bind iron. Following incubation with 2-PNE-PIH, the cells were exposed to 5 J/cm² UVA and then measured for changes in lipid peroxidation and ferritin levels. 2-PNE-PIH protected keratinocytes against UVA-induced lipid peroxidation and ferritin depletion. Further, 2-PNE-PIH was neither cytotoxic nor did it alter iron metabolism. 2-PNE-PIH may be a useful deterrent against UVA-induced oxidative stress in post-menopausal women. © 2011 John Wiley & Sons A/S.

  3. Microenvironmental pH is a key factor for exosome traffic in tumor cells.

    PubMed

    Parolini, Isabella; Federici, Cristina; Raggi, Carla; Lugini, Luana; Palleschi, Simonetta; De Milito, Angelo; Coscia, Carolina; Iessi, Elisabetta; Logozzi, Mariantonia; Molinari, Agnese; Colone, Marisa; Tatti, Massimo; Sargiacomo, Massimo; Fais, Stefano

    2009-12-04

    Exosomes secreted by normal and cancer cells carry and deliver a variety of molecules. To date, mechanisms referring to tumor exosome trafficking, including release and cell-cell transmission, have not been described. To gain insight into this, exosomes purified from metastatic melanoma cell medium were labeled with a lipid fluorescent probe, R18, and analyzed by spectrofluorometry and confocal microscopy. A low pH condition is a hallmark of tumor malignancy, potentially influencing exosome release and uptake by cancer cells. Using different pH conditions as a modifier of exosome traffic, we showed (i) an increased exosome release and uptake at low pH when compared with a buffered condition and (ii) exosome uptake by melanoma cells occurred by fusion. Membrane biophysical analysis, such as fluidity and lipid composition, indicated a high rigidity and sphingomyelin/ganglioside GM3 (N-acetylneuraminylgalactosylglucosylceramide) content in exosomes released at low pH. This was likely responsible for the increased fusion efficiency. Consistent with these results, pretreatment with proton pump inhibitors led to an inhibition of exosome uptake by melanoma cells. Fusion efficiency of tumor exosomes resulted in being higher in cells of metastatic origin than in those derived from primary tumors or normal cells. Furthermore, we found that caveolin-1, a protein involved in melanoma progression, is highly delivered through exosomes released in an acidic condition. The results of our study provide the evidence that exosomes may be used as a delivery system for paracrine diffusion of tumor malignancy, in turn supporting the importance of both exosomes and tumor pH as key targets for future anti-cancer strategies.

  4. Model for Microcapsule Drug Release with Ultrasound-Activated Enhancement.

    PubMed

    Tsao, Nadia H; Hall, Elizabeth A H

    2017-11-14

    Microbubbles and microcapsules of silane-polycaprolactone (SiPCL) have been filled with a fluorescent acridium salt (lucigenin) as a model for a drug-loaded delivery vehicle. The uptake and delivery were studied and compared with similar microbubbles and microcapsules of silica/mercaptosilica (S/M/S). Positively charged lucigenin was encapsulated through an electrostatic mechanism, following a Type I Langmuir isotherm as expected, but with an additional multilayer uptake that leads to a much higher loading for the SiPCL system (∼280 μg/2.4 × 10 9 microcapsules compared with ∼135 μg/2.4 × 10 9 microcapsules for S/M/S). Whereas the lucigenin release from the S/M/S bubbles and capsules loaded below the solubility limit is consistent with diffusion from a monolithic structure, the SiPCL structures show distinct release patterns; the Weibull function predicts a general trend for diffusion from normal Euclidean space at short times tending toward diffusion out of fractal spaces with increasing time. As a slow release system, the dissolution time (T d ) increases from 1 to 2 days for the S/M/S and for the low concentration, loaded SiPCl vehicles to ∼10 days for the high loaded microcapsules. However, T d can be reduced on insonation to 2 days, indicating the potential to gain control over the local enhanced release with ultrasound. This was tested for a docetaxel model and its effect on C4-2B prostate cancer cells, showing improved cell toxicity for concentrations below the normal EC 50 in solution.

  5. Source Term Estimates of Radioxenon Released from the BaTek Medical Isotope Production Facility Using External Measured Air Concentrations

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

    Eslinger, Paul W.; Cameron, Ian M.; Dumais, Johannes R.

    2015-10-01

    Abstract Batan Teknologi (BaTek) operates an isotope production facility in Serpong, Indonesia that supplies 99mTc for use in medical procedures. Atmospheric releases of Xe-133 in the production process at BaTek are known to influence the measurements taken at the closest stations of the International Monitoring System (IMS). The purpose of the IMS is to detect evidence of nuclear explosions, including atmospheric releases of radionuclides. The xenon isotopes released from BaTek are the same as those produced in a nuclear explosion, but the isotopic ratios are different. Knowledge of the magnitude of releases from the isotope production facility helps inform analystsmore » trying to decide whether a specific measurement result came from a nuclear explosion. A stack monitor deployed at BaTek in 2013 measured releases to the atmosphere for several isotopes. The facility operates on a weekly cycle, and the stack data for June 15-21, 2013 show a release of 1.84E13 Bq of Xe-133. Concentrations of Xe-133 in the air are available at the same time from a xenon sampler located 14 km from BaTek. An optimization process using atmospheric transport modeling and the sampler air concentrations produced a release estimate of 1.88E13 Bq. The same optimization process yielded a release estimate of 1.70E13 Bq for a different week in 2012. The stack release value and the two optimized estimates are all within 10 percent of each other. Weekly release estimates of 1.8E13 Bq and a 40 percent facility operation rate yields a rough annual release estimate of 3.7E13 Bq of Xe-133. This value is consistent with previously published estimates of annual releases for this facility, which are based on measurements at three IMS stations. These multiple lines of evidence cross-validate the stack release estimates and the release estimates from atmospheric samplers.« less

  6. Addressing Cancer Drug Costs and Value

    Cancer.gov

    The President’s Cancer Panel has released its latest report, Promoting Value, Affordability, and Innovation in Cancer Drug Treatment. The report recommends six actions to maximize the value and affordability of cancer drug treatment.

  7. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

    NASA Astrophysics Data System (ADS)

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-02-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.

  8. 48 CFR 215.404-71-1 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... range provides values based on above normal or below normal conditions. In the price negotiation..., DEPARTMENT OF DEFENSE CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Contract Pricing 215... contracting officer assigns values to each profit factor; the value multiplied by the base results in the...

  9. Predoctoral Fellowship to Study an ER Variant Identified from Breast Hyperplasias.

    DTIC Science & Technology

    1999-07-01

    Spl and Sp3 in Drosophila SL2 cells, which do not express any of the Spl family members. The plasmid pNull- Renilla (Promega) was co- transfected for...10 M. Luciferase values were normalized to Renilla luciferase expression. Fold induction was calculated relative to the normalized luciferase...to 10 M. Luciferase values were normalized to Renilla luciferase expression. Fold induction was calculated relative to the normalized luciferase

  10. Quantification of nanoparticle release from polymer nanocomposite coatings due to environmental stressing.

    PubMed

    Kim, Yeon Seok; Davis, Rick; Uddin, Nasir; Nyden, Marc; Rabb, Savelas A

    2016-01-01

    Certain engineered nanoparticles (ENP) reduce the flammability of components used in soft furnishings (mattresses and upholstered furniture). However, because of the ENP's small size and ability to interact with biological molecules, these fire retardant ENPs may pose a health and environmental risks, if they are released sometime during the life cycle of the soft furnishing. Quantifying the released amount of these ENPs under normal end-use circumstances provides a basis for assessing their potential health and environmental impact. In this article, we report on efforts to identify suitable methodologies for quantifying the release of carbon nanofibers, carbon nanotubes, and sodium montmorillonites from coatings applied to the surfaces of barrier fabric and polyurethane foam. The ENPs released in simulated chewing and mechanical stressing experiments were collected in aqueous solution and quantified using Ultraviolet-Visible and inductively coupled plasma-optical emission spectroscopy. The microstructures of the released ENPs were characterized using scanning electron microscopy. The reported methodology and results provide important milestones to estimate the impact and toxicity of the ENP release during the life cycle of the nanocomposites. To our knowledge, this is the first study of ENP release from the soft furnishing coating, something that can be important application area for fire safety.

  11. Process of formulating USDA's Expanded Flavonoid Database for the Assessment of Dietary intakes: a new tool for epidemiological research.

    PubMed

    Bhagwat, Seema A; Haytowitz, David B; Wasswa-Kintu, Shirley I; Pehrsson, Pamela R

    2015-08-14

    The scientific community continues to be interested in potential links between flavonoid intakes and beneficial health effects associated with certain chronic diseases such as CVD, some cancers and type 2 diabetes. Three separate flavonoid databases (Flavonoids, Isoflavones and Proanthocyanidins) developed by the USDA Agricultural Research Service since 1999 with frequent updates have been used to estimate dietary flavonoid intakes, and investigate their health effects. However, each of these databases contains only a limited number of foods. The USDA has constructed a new Expanded Flavonoids Database for approximately 2900 commonly consumed foods, using analytical values from their existing flavonoid databases (Flavonoid Release 3.1 and Isoflavone Release 2.0) as the foundation to calculate values for all the twenty-nine flavonoid compounds included in these two databases. Thus, the new database provides full flavonoid profiles for twenty-nine predominant dietary flavonoid compounds for every food in the database. Original analytical values in Flavonoid Release 3.1 and Isoflavone Release 2.0 for corresponding foods were retained in the newly constructed database. Proanthocyanidins are not included in the expanded database. The process of formulating the new database includes various calculation techniques. This article describes the process of populating values for the twenty-nine flavonoid compounds for every food in the dataset, along with challenges encountered and resolutions suggested. The new expanded flavonoid database released on the Nutrient Data Laboratory's website would provide uniformity in estimations of flavonoid content in foods and will be a valuable tool for epidemiological studies to assess dietary intakes.

  12. 21 CFR 177.1430 - Isobutylene-butene copolymers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Maximum bromine value 1. Used as release agents in petroleum wax complying with § 178.3710 of this chapter... release coatings on backings or linings for pressure-sensitive adhesive labels complying with § 175.125 of...

  13. Effect of particle size on calcium release and elevation of pH of endodontic cements.

    PubMed

    Saghiri, Mohammad Ali; Asatourian, Armen; Orangi, Jafar; Lotfi, Mehrdad; Soukup, Jason W; Garcia-Godoy, Franklin; Sheibani, Nader

    2015-06-01

    Elevation of pH and calcium ion release are of great importance in antibacterial activity and the promotion of dental soft and hard tissue healing process. In this study, we evaluated the effect of particle size on the elevation of pH and the calcium ion release from calcium silicate-based dental cements. Twelve plastic tubes were divided into three groups, filled with white mineral trioxide aggregate (WMTA), WMTA plus 1% methylcellulose, and nano-modified WMTA (nano-WMTA), and placed inside flasks containing 10 ml of distilled water. The pH values were measured using a pH sensor 3, 24, 72, and 168 h after setting of the cements. The calcium ion release was measured using an atomic absorption spectrophotometer with same sample preparation method. Data were subjected to two-way analysis of variance (anova) followed by post hoc Tukey tests with significance level of P < 0.05. Nano-WMTA showed significant pH elevation only after 24 h (P < 0.05) compared with WMTA, and after 3, 24, and 72 h compared with WMTA plus 1% methylcellulose (P < 0.05). Nano-WMTA showed significantly higher calcium ion release values compared to the other two groups (P < 0.05). Nano-modification of WMTA remarkably increased the calcium ion release at all time intervals postsetting, which can significantly influence the osteogenic properties of human dental pulp cells and as a consequence enhance mineralized matrix nodule formation to achieve desirable clinical outcomes. However, the increase in pH values mainly occurred during the short time postsetting. Addition of 1% methylcellulose imposed a delay in elevation of pH and calcium ion release by WMTA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Nanostructural control of the release of macromolecules from silica sol–gels

    PubMed Central

    Radin, Shula; Bhattacharyya, Sanjib; Ducheyne, Paul

    2013-01-01

    The therapeutic use of biological molecules such as growth factors and monoclonal antibodies is challenging in view of their limited half-life in vivo. This has elicited the interest in delivery materials that can protect these molecules until released over extended periods of time. Although previous studies have shown controlled release of biologically functional BMP-2 and TGF-β from silica sol–gels, more versatile release conditions are desirable. This study focuses on the relationship between room temperature processed silica sol–gel synthesis conditions and the nanopore size and size distribution of the sol–gels. Furthermore, the effect on release of large molecules with a size up to 70 kDa is determined. Dextran, a hydrophilic polysaccharide, was selected as a large model molecule at molecular sizes of 10, 40 and 70 kDa, as it enabled us to determine a size effect uniquely without possible confounding chemical effects arising from the various molecules used. Previously, acid catalysis was performed at a pH value of 1.8 below the isoelectric point of silica. Herein the silica synthesis was pursued using acid catalysis at either pH 1.8 or 3.05 first, followed by catalysis at higher values by adding base. This results in a mesoporous structure with an abundance of pores around 3.5 nm. The data show that all molecular sizes can be released in a controlled manner. The data also reveal a unique in vivo approach to enable release of large biological molecules: the use more labile sol–gel structures by acid catalyzing above the pH value of the isoelectric point of silica; upon immersion in a physiological fluid the pores expand to reach an average size of 3.5 nm, thereby facilitating molecular out-diffusion. PMID:23643607

  15. Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters.

    PubMed

    Pifl, Christian; Nagy, Gabor; Berényi, Sándor; Kattinger, Alexandra; Reither, Harald; Antus, Sándor

    2005-07-01

    Ecstasy samples often contain byproducts of the illegal, uncontrolled synthesis of N-methyl-3,4-methylenedioxy-amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). MDMA and eight chemically defined byproducts of MDMA synthesis were investigated for their interaction with the primary sites of action of MDMA, namely the human plasmalemmal monamine transporters for norepinephrine, serotonin, and dopamine [(norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT)]. SK-N-MC neuroblastoma and human embryonic kidney cells stably transfected with the transporter cDNA were used for uptake and release experiments. Two of the eight compounds, 1,3-bis (3,4-methylenedioxyphenyl)-2-propanamine (12) and N-formyl-1,3-bis (3,4-methylenedioxyphenyl)-prop-2-yl-amine (13) had uptake inhibitory potencies with IC50 values in the low micromolar range similar to MDMA. Compounds with nitro instead of amino groups and a phenylethenyl instead of a phenylethyl structure or a formamide or acetamide modification had IC50 values beyond 100 microM. MDMA, 12, and 13 were examined for induction of carrier-mediated release by superfusion of transporter expressing cells preloaded with the metabolically inert transporter substrate [3H]1-methyl-4-phenylpyridinium. MDMA induced release mediated by NET, SERT, or DAT with EC50 values of 0.64, 1.12, and 3.24 microM, respectively. 12 weakly released from NET- and SERT-expressing cells with maximum effects less than one-tenth of that of MDMA and did not release from DAT cells. 13 had no releasing activity. 12 and 13 inhibited release induced by MDMA, and the concentration dependence of this effect correlated with their uptake inhibitory potency at the various transporters. These results do not support a neurotoxic potential of the examined ecstasy synthesis byproducts and provide interesting structure-activity relationships on the transporters.

  16. In Vitro Analysis of Nanoparticulate Hydroxyapatite/Chitosan Composites as Potential Drug Delivery Platforms for the Sustained Release of Antibiotics in the Treatment of Osteomyelitis

    PubMed Central

    USKOKOVIĆ, VUK; DESAI, TEJAL A.

    2014-01-01

    Nanoparticulate composites of hydroxyapatite (HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one—HAp. Embedment of 5–10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, and promoted sustained-release kinetics throughout the 3 weeks of release time. The addition of chitosan to the particulate drug carrier formulation, however, reduced the antibacterial efficacy against S aureus. Excellent cell spreading and proliferation of osteoblastic MC3T3-E1 cells evidenced on microscopic conglomerates of HAp nanoparticles in vitro also markedly diminished on HAp/chitosan composites. Mitochondrial dehydrogenase activity exhibited normal values only for HAp/chitosan particle concentrations of up to 2 mg/cm2 and significantly dropped, by about 50%, at higher particle concentrations (4 and 8 mg/cm2). The gene expression of osteocalcin, a mineralization inductor, and the transcription factor Runx2 was downregulated in cells incubated in the presence of 3 mg/cm2 HAp/chitosan composite particles, whereas the expression of osteopontin, a potent mineralization inhibitor, was upregulated, further demonstrating the partially unfavorable osteoblastic cell response to the given particles. The peak in the expression of osteogenic markers paralleling the osteoblastic differentiation was also delayed most for the cell population incubated with HAp/chitosan particles. Overall, the positive effect of chitosan coating on the drug elution profile of HAp nanoparticles as carriers for the controlled delivery of antibiotics in the treatment of osteomyelitis was compensated for by the lower bacteriostatic efficiency and the comparatively unviable cell response to the composite material, especially at higher dosages. PMID:24382825

  17. Acetylcholine released from cholinergic nerves contributes to cutaneous vasodilation during heat stress

    NASA Technical Reports Server (NTRS)

    Shibasaki, Manabu; Wilson, Thad E.; Cui, Jian; Crandall, Craig G.

    2002-01-01

    Nitric oxide (NO) contributes to active cutaneous vasodilation during a heat stress in humans. Given that acetylcholine is released from cholinergic nerves during whole body heating, coupled with evidence that acetylcholine causes vasodilation via NO mechanisms, it is possible that release of acetylcholine in the dermal space contributes to cutaneous vasodilation during a heat stress. To test this hypothesis, in seven subjects skin blood flow (SkBF) and sweat rate were simultaneously monitored over three microdialysis membranes placed in the dermal space of dorsal forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine (10 microM), the second membrane was perfused with the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 10 mM) dissolved in the aforementioned neostigmine solution (l-NAME(Neo)), and the third membrane was perfused with Ringer solution as a control site. Each subject was exposed to approximately 20 min of whole body heating via a water-perfused suit, which increased mean body temperature from 36.4 +/- 0.1 to 37.5 +/- 0.1 degrees C (P < 0.05). After the heat stress, SkBF at each site was normalized to its maximum value, identified by administration of 28 mM sodium nitroprusside. Mean body temperature threshold for cutaneous vasodilation was significantly lower at the neostigmine-treated site relative to the other sites (neostigmine: 36.6 +/- 0.1 degrees C, l-NAME(Neo): 37.1 +/- 0.1 degrees C, control: 36.9 +/- 0.1 degrees C), whereas no significant threshold difference was observed between the l-NAME(Neo)-treated and control sites. At the end of the heat stress, SkBF was not different between the neostigmine-treated and control sites, whereas SkBF at the l-NAME(Neo)-treated site was significantly lower than the other sites. These results suggest that acetylcholine released from cholinergic nerves is capable of modulating cutaneous vasodilation via NO synthase mechanisms early in the heat stress but not after substantial cutaneous vasodilation.

  18. Does growth hormone releasing factor desensitize the somatotroph? Interpretation of responses of growth hormone during and after 10-hour infusion of GRF 1-29 amide in man.

    PubMed

    Davis, J R; Sheppard, M C; Shakespear, R A; Lynch, S S; Clayton, R N

    1986-02-01

    It is unclear whether growth hormone releasing factor (GRF) administration in vivo may desensitize the somatotroph. To investigate this possibility we have examined the effects of 10-h infusion of the equipotent 1-29 amide analogue of hpGRF on serum GH levels and on the subsequent GH response to a bolus dose of GRF (1-29). Four normal adult males received an intravenous infusion of 1-29 GRF (1 microgram/kg/h) from 0800 to 1800 h, with blood samples taken at 10 min intervals. A 100 micrograms intravenous bolus dose of GRF was given at 1800 h, and sampling continued for a further 90 min. GH levels were near or below the limit of detection (0.5 mU/l) throughout the control 10 h period. During GRF infusion there was increased GH release with pulses of irregular frequency and amplitude (up to 80 mU/l) continuing throughout the entire infusion period. There was no apparent reduction in total GH released towards the latter part of the infusion. On the control day, 100 micrograms GRF bolus increased mean (+/- SEM) GH from 0.82 +/- 0.21 mU/l to a peak of 59.0 +/- 44.8 mU/l (P less than 0.002). Following 10-GRF infusion, responses to bolus injection of GRF were reduced, but variable. In two subjects a small rise in GH levels occurred (basal 6.4 and 7.2 rising to peak values of 11.2 and 23.0 mU/l respectively). In the other two subjects, GH levels fell but in these the GRF bolus had coincided with a GH peak. The loss of GRF responsiveness after GRF infusion may be due to 'desensitization'.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Seismic b-values and its correlation with seismic moment and Bouguer gravity anomaly over Indo-Burma ranges of northeast India: Tectonic implications

    NASA Astrophysics Data System (ADS)

    Bora, Dipok K.; Borah, Kajaljyoti; Mahanta, Rinku; Borgohain, Jayanta Madhab

    2018-03-01

    b-value is one of the most significant seismic parameters for describing the seismicity of a given region at a definite time window. In this study, high-resolution map of the Gutenberg-Richter b-value, seismic moment-release, Bouguer gravity anomaly and fault-plane solutions containing faulting styles are analyzed in the Indo-Burma ranges of northeast India using the unified and homogeneous part of the seismicity record in the region (January 1964-December 2016). The study region is subdivided into few square grids of geographical window size 1° × 1° and b-values are calculated in each square grid. Our goal is to explore the spatial correlations and anomalous patterns between the b-value and parameters like seismic moment release, Bouguer gravity anomaly and faulting styles that can help us to better understand the seismotectonics and the state of present-day crustal stress within the Indo-Burma region. Most of the areas show an inverse correlation between b-value and seismic moment release as well as convergence rates. While estimating the b-value as a function of depth, a sudden increase of b-value at a depth of 50-60 km was found out and the receiver function modeling confirms that this depth corresponds to the crust-mantle transition beneath the study region. The region is also associated with negative Bouguer gravity anomalies and an inverse relation is found between Gravity anomaly and b-value. Comparing b-values with different faulting styles, reveal that the areas containing low b-values show thrust mechanism, while the areas associated with intermediate b-values show strike-slip mechanism. Those areas, where the events show thrust mechanism but containing a strike-slip component has the highest b-value.

  20. Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

    PubMed

    Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

    2011-10-09

    Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. New diagnostic tests of GH reserve.

    PubMed

    Martul, P; Pineda, J; Pombo, M; Peñalva, A; Bokser, L; Dieguez, C

    1993-01-01

    Pharmacological tests are essential for the diagnosis of growth hormone (GH) insufficiency. Obesity is a pathological state associated with blunted GH response to all the classical stimuli tested. In the present study, three new pharmacological stimuli for GH reserve were evaluated in three groups of subjects: Normal, GH-insufficient and normal growing obese children. Dexamethasone provokes a clear GH-response in normal children, whereas the response in the other 2 groups of patients is significantly diminished. Galanin-induced GH-secretion is significantly higher in normal than in obese children. GHRP-6 causes a potent GH release in normal children, higher than in GH-insufficiency or obesity. The overlap shown between GH-insufficient patients and normal children reduces the usefulness of the tests. Similar to the classical stimuli, the response to these new tests is also decreased in obesity.

  2. Speech-on-speech masking with variable access to the linguistic content of the masker speech for native and non-native speakers of English

    PubMed Central

    Calandruccio, Lauren; Bradlow, Ann R.; Dhar, Sumitrajit

    2013-01-01

    Background Masking release for an English sentence-recognition task in the presence of foreign-accented English speech compared to native-accented English speech was reported in Calandruccio, Dhar and Bradlow (2010). The masking release appeared to increase as the masker intelligibility decreased. However, it could not be ruled out that spectral differences between the speech maskers were influencing the significant differences observed. Purpose The purpose of the current experiment was to minimize spectral differences between speech maskers to determine how various amounts of linguistic information within competing speech affect masking release. Research Design A mixed model design with within- (four two-talker speech maskers) and between-subject (listener group) factors was conducted. Speech maskers included native-accented English speech, and high-intelligibility, moderate-intelligibility and low-intelligibility Mandarin-accented English. Normalizing the long-term average speech spectra of the maskers to each other minimized spectral differences between the masker conditions. Study Sample Three listener groups were tested including monolingual English speakers with normal hearing, non-native speakers of English with normal hearing, and monolingual speakers of English with hearing loss. The non-native speakers of English were from various native-language backgrounds, not including Mandarin (or any other Chinese dialect). Listeners with hearing loss had symmetrical, mild sloping to moderate sensorineural hearing loss. Data Collection and Analysis Listeners were asked to repeat back sentences that were presented in the presence of four different two-talker speech maskers. Responses were scored based on the keywords within the sentences (100 keywords/masker condition). A mixed-model regression analysis was used to analyze the difference in performance scores between the masker conditions and the listener groups. Results Monolingual speakers of English with normal hearing benefited when the competing speech signal was foreign-accented compared to native-accented allowing for improved speech recognition. Various levels of intelligibility across the foreign-accented speech maskers did not influence results. Neither the non-native English listeners with normal hearing, nor the monolingual English speakers with hearing loss benefited from masking release when the masker was changed from native-accented to foreign-accented English. Conclusions Slight modifications between the target and the masker speech allowed monolingual speakers of English with normal hearing to improve their recognition of native-accented English even when the competing speech was highly intelligible. Further research is needed to determine which modifications within the competing speech signal caused the Mandarin-accented English to be less effective with respect to masking. Determining the influences within the competing speech that make it less effective as a masker, or determining why monolingual normal-hearing listeners can take advantage of these differences could help improve speech recognition for those with hearing loss in the future. PMID:25126683

  3. Effects of osmotic-release methylphenidate on height and weight in children with attention-deficit hyperactivity disorder (ADHD) following up to four years of treatment.

    PubMed

    Durá-Travé, Teodoro; Yoldi-Petri, María Eugenia; Gallinas-Victoriano, Fidel; Zardoya-Santos, Patricia

    2012-05-01

    There is some controversy concerning \\the potential negative influence of methylphenidate on growth. The authors reviewed clinical records of 187 patients with attention-deficit hyperactivity disorder under treatment with methylphenidate. The patients' weight, height, and body mass index were measured at diagnosis and during 4 years of follow-up. The dose of methylphenidate was gradually increased up to 1.31 ± 0.2 mg/kg/d. At diagnosis, mean weight value was lower than mean weight expected for age by 0.697 kg. This difference increased to 4.274 kg (at 30 months of treatment), although it subsequently decreased to 1.588 kg (at 48 months of treatment). Mean value of height was lower than expected mean height for age by 0.42 cm at diagnosis. This difference increased to 2.69 cm (at 30 months of treatment), but it subsequently decreased to 0.83 cm (at 48 months of treatment). The relationship between nutritional status and the negative effects on the height curve in those patients would require nutritional optimization to return anthropometric variables to normal.

  4. Controllable Thermal Rectification Realized in Binary Phase Change Composites

    PubMed Central

    Chen, Renjie; Cui, Yalong; Tian, He; Yao, Ruimin; Liu, Zhenpu; Shu, Yi; Li, Cheng; Yang, Yi; Ren, Tianling; Zhang, Gang; Zou, Ruqiang

    2015-01-01

    Phase transition is a natural phenomenon happened around our daily life, represented by the process from ice to water. While melting and solidifying at a certain temperature, a high heat of fusion is accompanied, classified as the latent heat. Phase change material (PCM) has been widely applied to store and release large amount of energy attributed to the distinctive thermal behavior. Here, with the help of nanoporous materials, we introduce a general strategy to achieve the binary eicosane/PEG4000 stuffed reduced graphene oxide aerogels, which has two ends with different melting points. It's successfully demonstrated this binary PCM composites exhibits thermal rectification characteristic. Partial phase transitions within porous networks instantaneously result in one end of the thermal conductivity saltation at a critical temperature, and therefore switch on or off the thermal rectification with the coefficient up to 1.23. This value can be further raised by adjusting the loading content of PCM. The uniqueness of this device lies in its performance as a normal thermal conductor at low temperature, only exhibiting rectification phenomenon when temperature is higher than a critical value. The stated technology has broad applications for thermal energy control in macroscopic scale such as energy-efficiency building or nanodevice thermal management. PMID:25748640

  5. Water potential in excised leaf tissue. Comparison of a commercial dew point hygrometer and a thermocouple psychrometer on soybean, wheat, and barley

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

    Nelsen, C.E.; Safir, G.R.; Hanson, A.D.

    1978-01-01

    Leaf water potential (Psi/sub leaf/) determinations were made on excised leaf samples using a commercial dew point hygrometer (Wescor Inc., Logan, Utah) and a thermocouple psychrometer operated in the isopiestic mode. With soybean leaves (Glycine max L.), there was good agreement between instruments; equilibration times were 2 to 3 hours. With cereals (Triticum aestivum L. and Hordeum vulgare L.), agreement between instruments was poor for moderately wilted leaves when 7-mm-diameter punches were used in the hygrometer and 20-mm slices were used in the psychrometer, because the Psi/sub leaf/ values from the dew point hygrometer were too high. Agreement was improvedmore » by replacing the 7-mm punch samples in the hygrometer by 13-mm slices, which had a lower cut edge to volume ratio. Equilibration times for cereals were normally 6 to 8 hours. Spuriously high Psi/sub leaf/ values obtained with 7-mm leaf punches may be associated with the ion release and reabsorption that occur upon tissue excision; such errors evidently depend both on the species and on tissue water status.« less

  6. Controllable Thermal Rectification Realized in Binary Phase Change Composites

    NASA Astrophysics Data System (ADS)

    Chen, Renjie; Cui, Yalong; Tian, He; Yao, Ruimin; Liu, Zhenpu; Shu, Yi; Li, Cheng; Yang, Yi; Ren, Tianling; Zhang, Gang; Zou, Ruqiang

    2015-03-01

    Phase transition is a natural phenomenon happened around our daily life, represented by the process from ice to water. While melting and solidifying at a certain temperature, a high heat of fusion is accompanied, classified as the latent heat. Phase change material (PCM) has been widely applied to store and release large amount of energy attributed to the distinctive thermal behavior. Here, with the help of nanoporous materials, we introduce a general strategy to achieve the binary eicosane/PEG4000 stuffed reduced graphene oxide aerogels, which has two ends with different melting points. It's successfully demonstrated this binary PCM composites exhibits thermal rectification characteristic. Partial phase transitions within porous networks instantaneously result in one end of the thermal conductivity saltation at a critical temperature, and therefore switch on or off the thermal rectification with the coefficient up to 1.23. This value can be further raised by adjusting the loading content of PCM. The uniqueness of this device lies in its performance as a normal thermal conductor at low temperature, only exhibiting rectification phenomenon when temperature is higher than a critical value. The stated technology has broad applications for thermal energy control in macroscopic scale such as energy-efficiency building or nanodevice thermal management.

  7. Post-Activation Brain Warming: A 1-H MRS Thermometry Study

    PubMed Central

    Rango, Mario; Bonifati, Cristiana; Bresolin, Nereo

    2015-01-01

    Purpose Temperature plays a fundamental role for the proper functioning of the brain. However, there are only fragmentary data on brain temperature (Tbr) and its regulation under different physiological conditions. Methods We studied Tbr in the visual cortex of 20 normal subjects serially with a wide temporal window under different states including rest, activation and recovery by a visual stimulation-Magnetic Resonance Spectroscopy Thermometry combined approach. We also studied Tbr in a control region, the centrum semiovale, under the same conditions. Results Visual cortex mean baseline Tbr was higher than mean body temperature (37.38 vs 36.60, P<0.001). During activation Tbr remained unchanged at first and then showed a small decrease (-0.20 C°) around the baseline value. After the end of activation Tbr increased consistently (+0.60 C°) and then returned to baseline values after some minutes. Centrum semiovale Tbr remained unchanged through rest, visual stimulation and recovery. Conclusion These findings have several implications, among them that neuronal firing itself is not a major source of heat release in the brain and that there is an aftermath of brain activation that lasts minutes before returning to baseline conditions. PMID:26011731

  8. Eliciting the Intension of Drug Value Sets – Principles and Quality Assurance Applications

    PubMed Central

    Bahr, Nathan J.; Nelson, Scott D.; Winnenburg, Rainer; Bodenreider, Olivier

    2018-01-01

    Value sets (VSs) used in electronic clinical quality measures are lists of codes from standard terminologies (“extensional” VSs), whose purpose (“intension”) is not always explicitly stated. We elicited the intension for the 09/01/2014 release of extensional medication value sets by comparison to drug classes from the October 2014 release of RxClass. Value sets matched drug classes if they shared common ingredients, as evidenced by Jaccard similarity score. We elicited the intension of 80 extensional value sets. The average Jaccard similarity was 0.65 for single classes and 0.80 for combination classes, with 34% (27/80) of the value sets having high similarity scores. Manual review by a pharmacist indicated 51% (41/80) of the drug classes selected as the best mapping for a value set matched the intension reflected in that value set name. This approach has the potential for facilitating the development and maintenance of medication value sets. PMID:29295218

  9. EFFECT ON PERFUSION VALUES OF SAMPLING INTERVAL OF CT PERFUSION ACQUISITIONS IN NEUROENDOCRINE LIVER METASTASES AND NORMAL LIVER

    PubMed Central

    Ng, Chaan S.; Hobbs, Brian P.; Wei, Wei; Anderson, Ella F.; Herron, Delise H.; Yao, James C.; Chandler, Adam G.

    2014-01-01

    Objective To assess the effects of sampling interval (SI) of CT perfusion acquisitions on CT perfusion values in normal liver and liver metastases from neuroendocrine tumors. Methods CT perfusion in 16 patients with neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow, blood volume, mean transit time, permeability, and hepatic arterial fraction, for tumor and normal liver. CT perfusion values for the reference sampling interval of 0.5s (SI0.5) were compared with those of SI datasets of 1s, 2s, 3s and 4s, using mixed-effects model analyses. Results Increases in SI beyond 1s were associated with significant and increasing departures of CT perfusion parameters from reference values at SI0.5 (p≤0.0009). CT perfusion values deviated from reference with increasing uncertainty with increasing SIs. Findings for normal liver were concordant. Conclusion Increasing SIs beyond 1s yield significantly different CT perfusion parameter values compared to reference values at SI0.5. PMID:25626401

  10. Utility of Diffusion Weighted Magnetic Resonance Imaging with Multiple B Values in Evaluation of Pancreatic Malignant and Benign Lesions and Pancreatitis.

    PubMed

    Karadeli, Elif; Erbay, Gurcan; Parlakgumus, Alper; Koc, Zafer

    2018-02-01

    To determine the feasibility of diffusion-weighted imaging in evaluation of pancreatic lesions and in differentiation of benign from malignant lesions. Descriptive study. Baskent University Adana Teaching and Research Center, Adana, Turkey, between September 2013 and May 2015. Forty-three lesions [pancreas adenocarcinoma (n=25)], pancreatitis (n=10), benign lesion (n=8)] were utilized with diffusion-weighted magnetic resonance imaging with multiple b-values. Different ADC maps of diffusion weighted images by using b-values were acquired. The median ADC at all b values for malignant lesions was significantly different from that for benign lesions (p<0.001). When ADCs at all b values were compared between benign lesions/normal parenchyma and malignant lesions/normal parenchyma, there was a significant statistical difference in all b values between benign and malignant lesions except at b 50 and b 200 (p<0.05). The lesion/normal parenchyma ADC ratio for b 600 value (AUC=0.804) was more effective than the lesion ADC for b 600 value (AUC=0.766) in differentiation of benign and malignant lesions. The specificity and sensitivity of the lesion/normal parenchyma ADC ratio were higher than those of ADC values of lesions. When the ADC was compared between benign lesions and pancreatitis, a significant difference was found at all b values (p<0.001). There was not a statistically significant difference between the ADC for pancreatitis and that for malignant lesions at any b value combinations (p>0.05). Diffusion-weighted magnetic resonance images can be helpful in differentiation of pancreatic carcinoma and benign lesions. Lesion ADC / normal parenchyma ADC ratios are more important than lesion ADC values in assessment of pancreatic lesions.

  11. Informative graphing of continuous safety variables relative to normal reference limits.

    PubMed

    Breder, Christopher D

    2018-05-16

    Interpreting graphs of continuous safety variables can be complicated because differences in age, gender, and testing site methodologies data may give rise to multiple reference limits. Furthermore, data below the lower limit of normal are compressed relative to those points above the upper limit of normal. The objective of this study is to develop a graphing technique that addresses these issues and is visually intuitive. A mock dataset with multiple reference ranges is initially used to develop the graphing technique. Formulas are developed for conditions where data are above the upper limit of normal, normal, below the lower limit of normal, and below the lower limit of normal when the data value equals zero. After the formulae are developed, an anonymized dataset from an actual set of trials for an approved drug is evaluated comparing the technique developed in this study to standard graphical methods. Formulas are derived for the novel graphing method based on multiples of the normal limits. The formula for values scaled between the upper and lower limits of normal is a novel application of a readily available scaling formula. The formula for the lower limit of normal is novel and addresses the issue of this value potentially being indeterminate when the result to be scaled as a multiple is zero. The formulae and graphing method described in this study provides a visually intuitive method to graph continuous safety data including laboratory values, vital sign data.

  12. Petroleum and hazardous material releases from industrial facilities associated with Hurricane Katrina.

    PubMed

    Santella, Nicholas; Steinberg, Laura J; Sengul, Hatice

    2010-04-01

    Hurricane Katrina struck an area dense with industry, causing numerous releases of petroleum and hazardous materials. This study integrates information from a number of sources to describe the frequency, causes, and effects of these releases in order to inform analysis of risk from future hurricanes. Over 200 onshore releases of hazardous chemicals, petroleum, or natural gas were reported. Storm surge was responsible for the majority of petroleum releases and failure of storage tanks was the most common mechanism of release. Of the smaller number of hazardous chemical releases reported, many were associated with flaring from plant startup, shutdown, or process upset. In areas impacted by storm surge, 10% of the facilities within the Risk Management Plan (RMP) and Toxic Release Inventory (TRI) databases and 28% of SIC 1311 facilities experienced accidental releases. In areas subject only to hurricane strength winds, a lower fraction (1% of RMP and TRI and 10% of SIC 1311 facilities) experienced a release while 1% of all facility types reported a release in areas that experienced tropical storm strength winds. Of industrial facilities surveyed, more experienced indirect disruptions such as displacement of workers, loss of electricity and communication systems, and difficulty acquiring supplies and contractors for operations or reconstruction (55%), than experienced releases. To reduce the risk of hazardous material releases and speed the return to normal operations under these difficult conditions, greater attention should be devoted to risk-based facility design and improved prevention and response planning.

  13. 7 CFR 760.5 - Fair market value of milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... market value of the affected farmer's normal marketings, which, for the purposes of this subpart, shall be the sum of the net proceeds such farmer would have received for his normal marketings in each of... affected farmer's normal marketings for each such pay period by the average net price per hundred-weight of...

  14. Preformulation experiences and in vitro model studies with spironolactone-containing suppositories.

    PubMed

    Regdon, G; Deák, D; Regdon, G; Muskó, Z; Erös, I

    2001-01-01

    The optimal suppository base for the formulation of rectal suppositories containing diuretic spironolactone was selected experimentally. Model studies were carried out about the effect of solubility-increasing additives on the release of the drug from the suppositories. During the in vitro examinations acceptor phases of different pH values were used, and both diffusion time and the number of samplings were changed. Among the lipophilic and hydrophilic suppository bases studied the hydrophilic Macrogolum 1540 was found to be optimal. The release and diffusion of spironolactone was the most favourable from these suppositories. During storage these suppositories remained stable and the values of release did not decrease significantly (p < 0.05).

  15. Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules III. Effects of the dissolution condition on the release process.

    PubMed

    Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

    2006-08-01

    In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the entire release properties. As the first step, the dissolution test under various conditions is selected for the in vitro test, and usually the results are analyzed following Drug Approval and Licensing Procedures. In this test, 3 time points for each release ratio, such as 0.2-0.4, 0.4-0.6, and over 0.7, respectively, should be selected in advance. These are analyzed as to whether their values are inside or outside the prescribed aims at each time point. This method is very simple and useful but the details of the release properties can not be clarified or confirmed. The validity of the dissolution test in analysis using a combination of the square-root time law and cube-root law equations to understand all the drug release properties was confirmed by comparing the simulated value with that measured in the previous papers. Dissolution tests under various conditions affecting drug release properties in the human body were then examined, and the results were analyzed by both methods to identify their strengths and weaknesses. Hereafter, the control of pharmaceutical preparation, the manufacturing process, and understanding the drug release properties will be more efficient. It is considered that analysis using the combination of the square-root time law and cube-root law equations is very useful and efficient. The accuracy of predicting drug release properties in the human body was improved and clarified.

  16. Coatings from blends of Eudragit® RL and L55: a novel approach in pH-controlled drug release.

    PubMed

    Wulff, R; Leopold, C S

    2014-12-10

    The aim of the present study was to investigate the drug release from theophylline pellets coated with blends of quaternary polymethacrylate and methacrylic acid-ethyl acrylate copolymers. Pellets were coated with blends of Eudragit(®) RL PO (RL) and Eudragit(®) L 100-55 (L55) in either organic solution or aqueous dispersion at various copolymer ratios. Generally, the coatings were less permeable for theophylline in phosphate buffer pH 6.8 than they were in hydrochloric acid pH 1.2. Further dissolution experiments revealed that the differences in drug release are caused by the different pH values. A design of experiments for historical data was performed on drug release data of pellets with different coating levels and blend ratios of RL and L55. Drug release in hydrochloric acid was predominantly affected by the coating level, whereas for drug release in phosphate buffer pH 6.8 the blend ratio was the determining factor. As expected, dissolution experiments at different pH values showed that drug release depends on the ratio of dissociated L55 to RL because ionization is a requirement for the functional groups to interact. With the dissolution test for delayed-release solid dosage forms (Ph. Eur.) it was demonstrated that the unique release behavior in neutral media is preserved after the exposition to hydrochloric acid. These findings indicate that the combination of RL and L55 in coatings prepared from solutions is a promising approach for controlled drug release. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Genotoxic and reprotoxic effects of tritium and external gamma irradiation on aquatic animals.

    PubMed

    Adam-Guillermin, Christelle; Pereira, Sandrine; Della-Vedova, Claire; Hinton, Tom; Garnier-Laplace, Jacqueline

    2012-01-01

    Aquatic ecosystems are chronically exposed to natural radioactivity or to artificial radionuclides released by human activities (e.g., nuclear medicine and biology,nuclear industry, military applications). Should the nuclear industry expand in the future, radioactive environmental releases, under normal operating conditions or accidental ones, are expected to increase, which raises public concerns about possible consequences on the environment and human health. Radionuclide exposures may drive macromolecule alterations, and among macromolecules DNA is the major target for ionizing radiations. DNA damage, if not correctly repaired, may induce mutations, teratogenesis, and reproductive effects. As such, damage at the molecular level may have consequences at the population level. In this review, we present an overview of the literature dealing with the effects of radionuclides on DNA, development, and reproduction of aquatic organisms. The review focuses on the main radionuclides that are released by nuclear power plants under normal operating conditions, γ emitters and tritium. Additionally, we fitted nonlinear curves to the dose-response data provided in the reviewed publications and manuscripts, and thus obtained endpoints commonly associated with ecotoxicological studies, such as the EDR(10). These were then used as a common metric for comparing the values and data published in the literature.The effects of tritium on aquatic organisms were reviewed for dose rates that ranged from 29 nGy/day to 29 Gy/day. Although beta emission from tritium decay presents a rather special risk of damage to DNA, genotoxicity-induced by tritium has been scarcely studied. Most of the effects studied have related to reproduction and development. Species sensitivity and the form of tritium present are important factors that drive the ecotoxicity of tritium. We have concluded from this review that invertebrates are more sensitive to the effects of tritium than are vertebrates.Because several calculated EDR10 values are ten times lower than background levels of γ irradiation the results of some studies either markedly call into question the adequacy of the benchmark value of 0.24 mGy/day for aquatic ecosystems that was recommended by Garnier-Laplace et al. (2006), or the dose rate estimates made in the original research, from which our EDR(10) values were derived, were under estimated, or were inadequate. For γ irradiation, the effects of several different dose rates on aquatic organisms were reviewed, and these ranged from 1 mGy/day to 18 Gy/day. DNA damage from exposure to y irradiation was studied more often than for tritium, but the major part of the literature addressed effects on reproduction and development. These data sets support the benchmark value of 0.24 mGy/day, which is recommended to protect aquatic ecosystems. RBEs, that describe the relative effectiveness of different radiation types to produce the same biological effect, were calculated using the available datasets. These RBE values ranged from 0.06 to 14.9, depending on the biological effect studied, and they had a mean of 3.1 ± 3.7 (standard deviation). This value is similar to the RBE factors of 2-3 recommended by international organizations responsible for providing guidance on radiation safety. Many knowledge gaps remain relative to the biological effects produced from exposure to tritium and y emitters. Among these are: Dose calculations: this review highlights several EDR(10) values that are below the normal range of background radiation. One explanation for this result is that dose rates were underestimated from uncertainties linked to the heterogenous distribution of tritium in cells. Therefore, the reliability of the concept of average dose to organisms must be addressed. Mechanisms of DNA DBS repair: very few studies address the most deleterious form of DNA damage, which are DNA DBSs. Future studies should focus on identifying impaired DNA DBS repair pathways and kinetics, in combination with developmental and reproductive effects. The transmission of genetic damage to offspring, which is of primary concern in the human health arena. However, there has been little work undertaken to assess the potential risk from germ cell mutagens in aquatic organisms, although this is one of the means of extrapolating effects from subcellular levels to populations. Reproductive behavior that is linked to alterations of endocrine function. Despite the importance of reproduction for population dynamics, many key endpoints were scarcely addressed within this topic. Hence, there is, to our knowledge,only one study of courtship behavior in fish exposed to γ rays, while no studies of radionuclide effects on fish endocrine function exist. Recent technical advances in the field of endocrine disrupters can be used to assess the direct or indirect effects of radionuclides on endocrine function. Identifying whether resistance to radiation effects in the field result from adaptation or acclimation mechanisms. Organisms may develop resistance to the toxic effects of high concentrations of radionuclides. Adaptation occurs at the population level by genetic selection for more resistant organisms. To date, very few field studies exist in which adaptation has been addressed, despite the fact that it represents an unknown influence on observed biological responses.

  18. Cell-derived microparticles after exercise in individuals with G6PD Viangchan.

    PubMed

    Chanda, Makamas; Nantakomol, Duangdao; Suksom, Daroonwan; Palasuwan, Attakorn

    2015-07-16

    Glucose-6-phospate dehydrogenase (G6PD) deficient cells are sensitive to oxidative damage leading to the formation of microparticles (MPs). Therefore, we examined the concentration of MPs and changes in the antioxidant balance after an acute strenuous exercise (SEx) and moderate-intensity exercise (MEx). Eighteen healthy females (18-24 years) with G6PD normal and eighteen age-matched females with G6PD Viangchan (871G>A) were tested by running on a treadmill at their maximal oxygen uptake for SEx and at 75% of their maximal heart rate for MEx. It was found that SEx triggered the release of total microparticles (TTMPs) above baseline levels and remained significantly higher 45 minutes after the exercise in G6PD normal individuals. However, SEx-induced increase in TTMPs was significantly higher in G6PD Viangchan as compared to G6PD normal. In contrast, MEx did not to alter the release of TTMPs in both G6PD normal and Viangchan. Moreover, TTMPs concentrations were inversely correlated with G6PD activity (r =-0.82, P <  0.05) but positively correlated with MDA concentrations (r = 0.74, P <  0.05). Using cell specific antibodies, we determined that MPs were mainly derived from platelets and erythrocytes. Altogether, the present study indicates that G6PD Viangchan may participate in MEx without higher MPs concentration and oxidative stress compared with G6PD normal.

  19. Sleep patterning and behaviour in cats with pontine lesions creating REM without atonia.

    PubMed

    Sanford; Morrison; Mann; Harris; Yoo; Ross

    1994-12-01

    Lesions of the dorsal pontine tegmentum release muscle tone and motor behaviour, much of it similar to orienting during wakefulness, into rapid eye movement sleep (REM), a state normally characterized by paralysis. Sleep after pontine lesions may be altered, with more REM-A episodes of shorter duration compared to normal REM. We examined behaviour, ponto-geniculo-occipital (PGO) waves (which may be central markers of orienting) and sleep in lesioned cats: (i) to characterize the relationship of PGO waves to behaviour in REM-A; (ii) to determine whether post-lesion changes in the timing and duration of REM-A episodes were due to activity-related awakenings: and (iii) to determine whether alterations in sleep changed the circadian sleep/wake cycle in cats. Behavioural release in REM-A was generally related to episode length, but episode length was not necessarily shorter than normal REM in cats capable of full locomotion in REM-A. PGO wave frequency was reduced overall during REM-A, but was higher during REM-A with behaviour than during quiet REM-A without overt behaviour. Pontine lesions did not significantly alter the circadian sleep/wake cycle: REM-A had approximately the same Light/Dark distribution as normal REM. Differences in the patterning of normal REM and REM-A within sleep involve more than mere movement-induced awakenings. Brainstem lesions that eliminate the atonia of REM may damage neural circuitry involved in REM initiation and maintenance; this circuitry is separate from circadian control mechanisms.

  20. THE EFFECT OF ANTISERUM, ALONE AND WITH HYDROCORTISONE, ON FOETAL MOUSE BONES IN CULTURE

    PubMed Central

    Fell, Honor B.; Weiss, L.

    1965-01-01

    1. The effects of normal rabbit serum and of rabbit antiserum to whole foetal mouse tissues, on the isolated limb bones of late foetal mice were studied in organ culture, and the influence of hydrocortisone on these effects was investigated. 2. Unheated normal serum caused slight loss of metachromatic material from the cartilage matrix, and some resorption of both cartilage and bone. 3. In unheated antiserum to foetal mouse tissues, the terminal cartilage was smaller and less metachromatic than in paired controls in normal serum, while osteoclasis was so intense that in many explants the bone had almost disappeared. The amount of necrosis varied with different batches of antiserum. 4. The changes produced by normal serum and antiserum could be largely prevented by heating the sera to 57°C for 45 minutes. 5. The effects could also be inhibited by the addition of hydrocortisone to the unheated sera; as little as 0.1 µg hydrocortisone per ml of medium had a well marked protective action. 6. It is suggested that (a) unheated antiserum causes a release of lysosomal enzymes with consequent breakdown of intercellular material, (b) this release is due to an indirect action on the lysosome via an increased permeability of the cell membrane, (c) hydrocortisone does not affect the antigen-antibody reaction, but inhibits the autolytic changes that normally follow this reaction, possibly by stabilising both the lysosomal and cell membranes. PMID:14276776

  1. Circulating autoantibodies to recombinant lipocortin-1 in asthma.

    PubMed

    Chung, K F; Podgorski, M R; Goulding, N J; Godolphin, J L; Sharland, P R; O'Connor, B; Flower, R J; Barnes, P J

    1991-03-01

    One of the postulated mechanisms of corticosteroid action is through the de novo synthesis and release of lipocortins. We assayed circulating antibodies to lipocortin-1 in sera obtained from normal (n = 67) and asthmatic (n = 57) subjects using an ELISA technique. Asthmatic subjects with a wide range of severity, with the mildest needing only occasional inhaled beta-agonist therapy to the most severe needing maintenance oral corticosteroid treatment, were recruited from our Asthma Clinic and classified into five categories according to the need of therapy. Median values of IgM and IgG lipocortin-1 antibody for normal subjects were 19.3 (interquartile range (r) = 11.0-30.4) and 16.9 (r = 10.54-29.4) ELISA units (EU) ml-1 respectively. These levels were significantly elevated in asthmatic subjects: IgM = 43.9 EU ml-1 (r = 31.7-64.5) and IgG = 29.0 EU ml-1 (r = 21.2-44.7) (P less than 0.001). There was no significant relationship between the levels of lipocortin antibody and the clinical severity of asthma. Asthmatics with significantly raised levels of antibody were found within all five categories of severity. We conclude that the level of this antibody is not related to severity of asthma, to previous or current corticosteroid therapy or to the development of corticosteroid resistance.

  2. Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells

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

    Vaca, Pilar; Berna, Genoveva; Araujo, Raquel

    2008-03-10

    The poly(ADP-ribose) polymerase (PARP) inhibitor, nicotinamide, induces differentiation and maturation of fetal pancreatic cells. In addition, we have previously reported evidence that nicotinamide increases the insulin content of cells differentiated from embryonic stem (ES) cells, but the possibility of nicotinamide acting as a differentiating agent on its own has never been completely explored. Islet cell differentiation was studied by: (i) X-gal staining after neomycin selection; (ii) BrdU studies; (iii) single and double immunohistochemistry for insulin, C-peptide and Glut-2; (iv) insulin and C-peptide content and secretion assays; and (v) transplantation of differentiated cells, under the kidney capsule, into streptozotocin (STZ)-diabetic mice.more » Here we show that undifferentiated mouse ES cells treated with nicotinamide: (i) showed an 80% decrease in cell proliferation; (ii) co-expressed insulin, C-peptide and Glut-2; (iii) had values of insulin and C-peptide corresponding to 10% of normal mouse islets; (iv) released insulin and C-peptide in response to stimulatory glucose concentrations; and (v) after transplantation into diabetic mice, normalized blood glucose levels over 7 weeks. Our data indicate that nicotinamide decreases ES cell proliferation and induces differentiation into insulin-secreting cells. Both aspects are very important when thinking about cell therapy for the treatment of diabetes based on ES cells.« less

  3. Effect of Sarcoplasmic Reticulum (SR) Calcium Content on SR Calcium Release Elicited by Small Voltage-Clamp Depolarizations in Frog Cut Skeletal Muscle Fibers Equilibrated with 20 mM EGTA

    PubMed Central

    Pape, Paul C.; Carrier, Nicole

    1998-01-01

    Cut muscle fibers from Rana temporaria (sarcomere length, 3.5–3.9 μm; 14–16°C) were mounted in a double Vaseline-gap chamber and equilibrated with an external solution that contained tetraethyl ammonium– gluconate and an internal solution that contained Cs as the principal cation, 20 mM EGTA, and 0 Ca. Fibers were stimulated with a voltage-clamp pulse protocol that consisted of pulses to −70, −65, −60, −45, and −20 mV, each separated by 400-ms periods at −90 mV. The change in total Ca that entered into the myoplasm (Δ[CaT]) and the Ca content of the SR ([CaSR]) were estimated with the EGTA/phenol red method (Pape, P.C., D.-S. Jong, and W.K. Chandler. 1995. J. Gen. Physiol. 106:259–336). Fibers were stimulated with the pulse protocol, usually every 5 min, so that the resting value of [CaSR] decreased from its initial value of 1,700–2,300 μM to values near or below 100 μM after 18–30 stimulations. Three main findings for the voltage pulses to −70, −65, and −60 mV are: (a) the depletion-corrected rate of Ca release (release permeability) showed little change when [CaSR] decreased from its highest level (>1,700 μM) to ∼1,000 μM; (b) as [CaSR] decreased below 1,000 μM, the release permeability increased to a maximum level when [CaSR] was near 300 μM that was on average about sevenfold larger than the values observed for [CaSR] > 1,000 μM; and (c) as [CaSR] decreased from ∼300 μM to <100 μM, the release permeability decreased, reaching half its maximum value when [CaSR] was ∼110 μM on average. It was concluded that finding b was likely due to a decrease in Ca inactivation, while finding c was likely due to a decrease in Ca-induced Ca release. PMID:9689025

  4. 19 CFR 351.404 - Selection of the market to be used as the basis for normal value.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... value. (a) Introduction. Although in most circumstances sales of the foreign like product in the home... market if the Secretary is satisfied that sales of the foreign like product in that country are of... use of sales to a third country or constructed value as the basis for normal value. This section...

  5. 10 CFR 72.100 - Defining potential effects of the ISFSI or MRS on the region.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... in the region resulting from the release of radioactive materials under normal and accident... with respect to the effects on the regional environment resulting from construction, operation, and...

  6. Release modeling and comparison of nanoarchaeosomal, nanoliposomal and pegylated nanoliposomal carriers for paclitaxel.

    PubMed

    Movahedi, Fatemeh; Ebrahimi Shahmabadi, Hasan; Alavi, Seyed Ebrahim; Koohi Moftakhari Esfahani, Maedeh

    2014-09-01

    Breast cancer is the most prevalent cancer among women. Recently, delivering by nanocarriers has resulted in a remarkable evolution in treatment of numerous cancers. Lipid nanocarriers are important ones while liposomes and archaeosomes are common lipid nanocarriers. In this work, paclitaxel was used and characterized in nanoliposomal and nanoarchaeosomal form to improve efficiency. To increase stability, efficiency and solubility, polyethylene glycol 2000 (PEG 2000) was added to some samples. MTT assay confirmed effectiveness of nanocarriers on MCF-7 cell line and size measuring validated nano-scale of particles. Nanoarchaeosomal carriers demonstrated highest encapsulation efficiency and lowest release rate. On the other hand, pegylated nanoliposomal carrier showed higher loading efficiency and less release compared with nanoliposomal carrier which verifies effect of PEG on improvement of stability and efficiency. Additionally, release pattern was modeled using artificial neural network (ANN) and genetic algorithm (GA). Using ANN modeling for release prediction, resulted in R values of 0.976, 0.989 and 0.999 for nanoliposomal, pegylated nanoliposomal and nanoarchaeosomal paclitaxel and GA modeling led to values of 0.954, 0.951 and 0.976, respectively. ANN modeling was more successful in predicting release compared with the GA strategy.

  7. Male acquired hypogonadotropic hypogonadism: diagnosis and treatment.

    PubMed

    Salenave, Sylvie; Trabado, Sévérine; Maione, Luigi; Brailly-Tabard, Sylvie; Young, Jacques

    2012-04-01

    Acquired hypogonadotropic hypogonadism (AHH), contrary to congenital hypogonadotropic hypogonadism (CHH) is characterized by postnatal onset of disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. AHH thus prevents the establishment of gonadotropin secretion at puberty, or its post-pubertal maintenance. Thus, postnatal AHH may prevent the onset of puberty or appear during pubertal development, but it usually emerges after the normal age of puberty. Although pituitary tumors, particularly prolactinoma, are the most common cause, sellar tumors or cyst of the hypothalamus or infundibulum, infiltrative, vascular, iron overload and other disorders may also cause AHH. Pituitary surgery and head trauma or cranial/pituitary radiation therapy are also usual causes of AHH. The clinical manifestations of AHH depend on age of onset, the degree of gonadotropin deficiency, the rapidity of its onset and the association to other pituitary function deficiencies or excess. Men with AHH have less stamina, decreased libido, erectile dysfunction and strength, and a worsened sense of well being leading to degraded quality of life. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial, body hair and muscle mass, fine facial wrinkles, gynecomastia, and hypotrophic testes are observed in long-standing and complete AHH. Spermatogenesis is impaired and the volume of ejaculate is decreased only when gonadotropins and testosterone levels are very low. Men with AHH may have normal or low serum LH and FSH concentrations, but normal gonadotropin values are inappropriate when associated with low serum testosterone. In the majority of AHH patients, serum inhibin B is "normal". The decrease of this sertolian hormone indicates a long-standing and severe gonadotropin deficiency. Symptoms, usually associated with significant testosterone deficiency in men with AHH, improve with testosterone replacement therapy. Replacement therapy is often simple, using an injectable testosterone ester as first line treatment. Fertility can be restored rather quickly, provided there is no independent primary testicular damage and the partner is fertile. Copyright © 2012. Published by Elsevier Masson SAS.

  8. Developing Normal Turns-Amplitude Clouds for Upper and Lower Limbs.

    PubMed

    Jabre, Joe F; Nikolayev, Sergey G; Babayev, Michael B; Chindilov, Denis V; Muravyov, Anatoly Y

    2016-10-01

    Turns and amplitude analysis (T&A) is a frequently used method for automatic EMG interference pattern analysis. The T&A normal values have only been developed for a limited number of muscles. Our objective was to obtain normal T&A clouds for upper and lower extremity muscles for which no normal values exist in the literature. The T&A normative data using concentric needle electrodes were obtained from 68 men and 56 women aged 20 to 60 years. Normal upper and lower extremity T&A clouds were obtained and presented in this article. The T&A normal values collected in this study maybe used to detect neurogenic and myopathic abnormalities in men and women at low-to-moderate muscle contractions. The effect of turns-amplitude data obtained at high force level of muscle contraction and its potential to falsely show neurogenic abnormalities are discussed.

  9. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage.

    PubMed

    Kaleemullah, M; Jiyauddin, K; Thiban, E; Rasha, S; Al-Dhalli, S; Budiasih, S; Gamal, O E; Fadli, A; Eddy, Y

    2017-07-01

    Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor ( f 2 ) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f 2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05) between the F3 and reference drug in terms of MDT and T50% with p-values of 1.00 and 0.995 respectively.

  10. Contrast-enhanced 3T MR Perfusion of Musculoskeletal Tumours: T1 Value Heterogeneity Assessment and Evaluation of the Influence of T1 Estimation Methods on Quantitative Parameters.

    PubMed

    Gondim Teixeira, Pedro Augusto; Leplat, Christophe; Chen, Bailiang; De Verbizier, Jacques; Beaumont, Marine; Badr, Sammy; Cotten, Anne; Blum, Alain

    2017-12-01

    To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. • T1 value variation in musculoskeletal tumours is considerable. • T1 values in muscle and tumours are significantly different. • Patient-specific T1 estimation is needed for comparison of inter-patient perfusion parameters. • Technical variation is higher in permeability than semiquantitative perfusion parameters.

  11. Continuous cardiac troponin I release in Fabry disease.

    PubMed

    Feustel, Andreas; Hahn, Andreas; Schneider, Christian; Sieweke, Nicole; Franzen, Wolfgang; Gündüz, Dursun; Rolfs, Arndt; Tanislav, Christian

    2014-01-01

    Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD. cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females) regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI). Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05-0.71 ng/ml, normal: <0.01). cMRI disclosed late gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3) in cardiomyocytes. Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD.

  12. CPTAC Releases Cancer Proteome Confirmatory Breast Study Data | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    An estimated 252,710 new cases of female breast cancer, accounting for 15% of all new cancer cases, occurred in 2017. To better understand proteogenomic abnormalities in breast cancer, the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) announces the release of the cancer proteome confirmatory breast study data. The goal of the study was to comprehensively characterize the proteome and phosphoproteome on approximately 100 prospectively collected breast tumor and adjacent normal tissues.

  13. Relatchable launch restraint mechanism for deployable booms

    NASA Technical Reports Server (NTRS)

    Warden, Robert M.

    1990-01-01

    A new Relatchable Launch Mechanism was developed which enables a deployable system to be restrained and released repeatedly rather than the normal one shot release systems of the past. The deployable systems are of the self extending type which rely on a lanyard attached to a drive motor to control the deployment and retraction. The Relatch Mechanism uses the existing drive motor to also actuate the latch. The design and kinematics of the Relatch Mechanism as used on two flight programs are described.

  14. Nucleus Accumbens Shell Dopamine Preferentially Tracks Information Related to Outcome Value of Reward.

    PubMed

    Sackett, Deirdre A; Saddoris, Michael P; Carelli, Regina M

    2017-01-01

    Effective decision-making requires organisms to predict reward values and bias behavior toward the best available option. The mesolimbic dopamine system, including the nucleus accumbens (NAc) shell and core, is involved in this process. Although studies support a role of the shell and core in specific aspects of decision-making (e.g., risk, effort, delay), no studies have directly compared dopamine release dynamics in these subregions to cues exclusively signaling the availability of different reward magnitudes. Here, fast-scan cyclic voltammetry was used to compare rapid dopamine release dynamics in the NAc subregions during a magnitude-based decision-making task. Rats learned that distinct cues signaled the availability of either a small or large reward (one or two sugar pellets), and then were given an opportunity to choose their preferred option. We found that peak dopamine release tracked the more preferred (higher-magnitude) option in both core and shell subregions. Critically, however, overall (i.e., global) dopamine release was significantly higher and longer lasting in the shell and tracked the preferred magnitude during the entire cue period. Further, in the shell (not core), dopamine signaling significantly declined immediately at the lever press for reward but increased during the period of reward consumption. Collectively, the results indicate that although dopamine release in both the core and shell are activated by cues signaling the opportunity to respond for rewards of different magnitudes, dopamine release in the shell plays a differential and unique role in tracking information related to the outcome value of reward.

  15. Occurrence and estrogenic activity of steroid hormones in Chinese streams: A nationwide study based on a combination of chemical and biological tools.

    PubMed

    Yao, Bo; Li, Rui; Yan, Shuwen; Chan, Shen-An; Song, Weihua

    2018-05-18

    Steroid hormones (SHs) are continuously released into the aquatic environment through various pathways after being excreted by humans and animals, interfere with the normal function of the endocrine system and may affect the physiology and reproduction of exposed aquatic life. To conduct a nationwide investigation of the occurrence and biological effects of SHs in surface river/steam water in China, we quantitated 27 selected SHs in 217 surface water samples by solid-phase extraction (SPE) tandem LC-MS/MS and used a recombinant yeast estrogen assay to screen extracts of the water samples for estrogenic activities. SHs were commonly found in the surface water samples, and their levels were typically in the ng L -1 range. Estrone (E1) and estriol (E3) were normally present in several to dozens of times higher concentrations than estradiol (E2) and 17-a-Ethinylestradiol (EE2). The high concentrations (mean > 1 μg L -1 ) of Sum SHs were primarily obtained in areas under extreme water stress, specifically the eastern coastal areas. Source apportionment based on the profiles of the target compounds indicated that 54.5% of the SHs in target samples came from freshly discharged untreated sewage. The estrogen equivalent (EEQ (bio) ) values ranged from 0.01 to 40.27 ng L -1 , and the calculated EEQ (EEQ (cal) ) values were generally lower than the corresponding EEQ (bio) values for all samples. E2 was the main contributor to the estrogenicity among the three estrogens, with a contribution ratio of 82.8%. The risk quotient values of E2 were highest and ranged from 1.55 to 782.95, and 76.0% of the target surface samples displayed the greatest environmental risk. We concluded that the impacts of SHs on humans in Chinese surface waters should not be ignored and that certain actions should be taken to decrease the levels of SHs in source waters, especially measures targeting SHs in untreated wastewater from the vast rural areas. Copyright © 2018. Published by Elsevier Ltd.

  16. [The regulation of FSH release by the testis. Studies on inhibin].

    PubMed

    Krause, W

    1977-05-12

    The FSH release from the hypophysis is suggested to be particularly regulated by a testicular hormone called inhibin. Origin, structure and target organs of inhibin are unknown. Experiments to test some hypotheses in this field are described. Adult male rats, prenatally treated with busulfan, show only Sertoli cells in the semiferous tubules. Experimental cryptorchidism and orchidectomy, however, leads to an increase in FSH levels as observed in normal animals. This indicates the role of Sertoli cells in FSH regulation. Ligation of efferent ducts of testes leads to an increase of FSH levels, too, indicating that an FSH-inhibiting principle cannot be absorbed. Interstitial testis fluid (ITF) of normal rats was applicated to immature female rats. Their FSH release is inhibited, visible in the lower ovarian weight gain following additional hCG-administration. Orchidectomized animals react with a decrease of FSH levels to the application of ITF. Therefore ITF seems to contain a FSH-inhibiting factor. Androgen binding protein-content of epididymes, however, is increased after repeated injections of ITF. It is concluded that testis (probably the Sertoli cells) produces a FSH-inhibiting factor, but ITF contains only small amounts of inhibin.

  17. Feasibility and preliminary safety of nitric oxide releasing solution as a treatment for bovine mastitis.

    PubMed

    Regev, Gilly; Martins, James; Sheridan, Michael P; Leemhuis, Jonathan; Thompson, James; Miller, Christopher

    2018-06-01

    Nitric oxide-releasing solution (NORS) is a liquid formulation that releases nitric oxide, a broad spectrum antimicrobial, single electron nitroxide radical. This solution was investigated as a potential antimicrobial treatment for bovine mastitis (BM). Three experiments were performed: a) NORS' effect on Staphylococcus aureus and Escherichia coli in an in vitro model; b) NORS' effect on milk obtained from dairy cows showing symptoms of clinical mastitis; and c) the consequences of administering NORS to healthy milking cattle using a dose-escalating in vivo study. Metabolite concentrations were estimated in their blood for methaemoglobin and nitrite; also, milk nitrite concentration and somatic cell count (SCC) were measured to study possible mammary gland inflammation following treatment. NORS lowered the bacterial concentration in all infected samples, in a time- and milk-diluted dependant fashion. Blood methemoglobin concentrations following treatment were all within the normal range for cattle. However, blood and milk nitrite concentrations increased initially but, during the next 24 h, returned to normal range, as did SCC, without any clinical signs of mammary gland inflammation. NORS, if shown to be effective, could be an alternative treatment for mastitis with a shorter clearance time. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Feasibility of laser-targeted photoocclusion of the choriocapillary layer in rats.

    PubMed

    Asrani, S; Zou, S; D'Anna, S; Lutty, G; Vinores, S A; Goldberg, M F; Zeimer, R

    1997-12-01

    A new method, laser-targeted photoocclusion, was developed to occlude choroidal neovascularization while minimizing damage to the overlying retina. The ability to occlude normal choriocapillary layer in rats was evaluated as a first test of the feasibility of treating choroidal neovascularization with this method. A photosensitive agent, aluminum phthalocyanine tetrasulfonate, encapsulated in heat-sensitive liposomes, was administered intravenously along with carboxyfluorescein liposomes. A low-power argon laser (retinal power density of 5.7 W/cm2) locally released a photosensitizer bolus, monitored by the simultaneous release of carboxyfluorescein. A diode laser (operating at 675 nm with a retinal power density of 0.27 W/cm2) activated the photosensitizer with its release. Vessels in the choriocapillary layer were occluded at day 3 after laser treatment and remained unchanged during the 30-day follow-up. Larger choroidal vessels and retinal capillaries remained perfused. Control experiments excluded possible effects of heat or activation of free photosensitizer. Pilot histologic studies showed no damage to the retinal pigment epithelium. Laser-targeted photoocclusion caused selective occlusion of normal choriocapillaries while sparing overlying retinal pigment epithelium and retinal vessels. The method has potential as a treatment of choroidal neovascularization that may minimize iatrogenic loss of vision.

  19. Silk fibroin nanoparticles prepared by electrospray as controlled release carriers of cisplatin.

    PubMed

    Qu, Jing; Liu, Yu; Yu, Yanni; Li, Jing; Luo, Jingwan; Li, Mingzhong

    2014-11-01

    To maintain the anti-tumor activity of cis-dichlorodiamminoplatinum (CDDP) while avoiding its cytotoxicity and negative influence on normal tissue, CDDP-loaded silk fibroin nanoparticles approximately 59 nm in diameter were successfully prepared by electrospray without using organic solvent. CDDP was incorporated into nanoparticles through metal-polymer coordination bond exchange. In vitro release tests showed that the cisplatin in the nanoparticles could be slowly and sustainably released for more than 15 days. In vitro anti-cancer experiments and intracellular Pt content testing indicated that CDDP-loaded silk fibroin nanoparticles were easily internalized by A549 lung cancer cells, transferring CDDP into cancer cells and then triggering their apoptosis. In contrast, the particles were not easily internalized by L929 mouse fibroblast cells and hence showed weaker cell growth inhibition. The CDDP-loaded silk fibroin nanoparticles showed sustained and efficient killing of tumor cells but weaker inhibition of normal cells. In general, this study provides not only a novel method for preparing CDDP-loaded silk fibroin nanoparticles but also a new carrier system for clinical therapeutic drugs against lung cancers and other tumors. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Dynamic release and clearance of circulating microparticles during cardiac stress.

    PubMed

    Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

    2014-01-03

    Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

  1. RANTES release by human airway smooth muscle: effects of prostaglandin E(2) and fenoterol.

    PubMed

    Lazzeri, N; Belvisi, M G; Patel, H J; Chung, K F; Yacoub, M H; Mitchell, J A

    2001-12-21

    In human airway smooth muscle cells, the levels of RANTES were increased upon stimulation with interleukin-1beta together with tumour necrosis factor-alpha (TNF-alpha) (10 ng ml(-1) for each). In this study, we have assessed the effects of prostaglandin E(2) and the beta(2)-adrenoceptor agonist, fenoterol on RANTES (regulated upon activation, normal T cell expressed and secreted) release by these cells. The levels of RANTES released by human airway smooth muscle cells were measured after 24 h of treatment. Prostaglandin E(2) and fenoterol, only in presence of a cyclo-oxygenase inhibitor indomethacin (10(-6) M), provoked a concentration-dependent reduction in RANTES release. These data suggest that, in settings where cyclo-oxygenase activity is low, both drugs may relieve the symptoms of airway diseases by reducing RANTES production.

  2. Poly(ethylene glycol)/chitosan/sodium glycerophosphate gel replaced the joint capsule with slow-release lubricant after joint surgery.

    PubMed

    Lu, Hailin; Ren, Shanshan; Li, Xing; Guo, Junde; Dong, Guangneng; Li, Jianhui; Gao, Li

    2018-08-01

    Body fluid is normally the only lubricant after joint replacement surgery, but wear problems have occurred because body fluid has poor lubrication ability. However, traditional lubricant would be diluted by body fluids and then absorbed by the human body. Therefore, an injectable gel with the ability to slow-release lubricant was designed to replace the joint capsule. The proposed gel, poly(ethylene glycol)/chitosan/sodium glycerophosphate (PEG/CS/GP) composite gel was then tested. The tribology results showed that the PEG/CS/GP gel had excellent slow-release properties, especially under pressure, and the PEG played an important role in improving the gel's rheological and mechanical properties. Moreover, this study revealed that the release solution had a good lubrication effect because the PEG and GP could crosslink via the hydrogen bond effect.

  3. Lactate dehydrogenase test

    MedlinePlus

    Normal value range is 105 to 333 international units per liter (IU/L). Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your provider about ...

  4. Tertiary structural changes and iron release from human serum transferrin.

    PubMed

    Mecklenburg, S L; Donohoe, R J; Olah, G A

    1997-08-01

    Iron release from human serum transferrin was investigated by comparison of the extent of bound iron, measured by charge transfer absorption band intensity (465 nm), with changes observed by small-angle solution X-ray scattering (SAXS) for a series of equilibrated samples between pH 5.69 and 7.77. The phosphate buffers used in this study promote iron release at relatively high pH values, with an empirical pK of 6.9 for the convolved release from the two sites. The spectral data reveal that the N-lobe release is nearly complete by pH 7.0, while the C-lobe remains primarily metal-laden. Conversely, the radius of gyration, Rg, determined from the SAXS data remains constant between pH 7.77 and 7.05, and the evolution of Rg between its value observed for the diferric protein at pH 7.77 (31.2+/-0.2 A) and that of the apo protein at pH 5.69 (33.9+/-0.4 A) exhibits an empirical pK of 6.6. While Rg is effectively constant in the pH range associated with iron release from the N-lobe, the radius of gyration of cross-section, Rc, increases from 16.9+/-0.2 A to 17.6+/-0.2 A. Model simulations suggest that two different rotations of the NII domain relative to the NI domain about a hinge deep in the iron-binding cleft of the N-lobe, one parallel with and one perpendicular to the plane of the iron-binding site, can be significantly advanced relative to their holo protein positions while yielding constant Rg and increased Rc values consistent with the scattering data. Rotation of the CII domain parallel with the C-lobe iron-binding site plane can partially account for the increased Rg values measured at low pH; however, no reasonable combined repositioning of the NII and CII domains yields the experimentally observed increase in Rg.

  5. Contributions of two types of calcium channels to synaptic transmission and plasticity.

    PubMed

    Edmonds, B; Klein, M; Dale, N; Kandel, E R

    1990-11-23

    In Aplysia sensory and motor neurons in culture, the contributions of the major classes of calcium current can be selectively examined while transmitter release and its modulation are examined. A slowly inactivating, dihydropyridine-sensitive calcium current does not contribute either to normal synaptic transmission or to any of three different forms of plasticity: presynaptic inhibition, homosynaptic depression, and presynaptic facilitation. This current does contribute, however, to a fourth form of plasticity--modulation of transmitter release by tonic depolarization of the sensory neuron. By contrast, a second calcium current, which is rapidly inactivating and dihydropyridine-insensitive, contributes to release elicited by the transient depolarization of an action potential and to the other three forms of plasticity.

  6. Ecological and toxicological aspects of the partial meltdown of the Chernobyl nuclear power plant reactor

    USGS Publications Warehouse

    Eisler, Ronald; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    1995-01-01

    the partial meltdown of the 1000-MW reactor at Chernobyl, Ukraine, on April 26, 1986, released large amounts of radiocesium and other radionuclides into the environment, causing widespread radioactive contamination of Europe and the former Soviet Union.1-7 At least 3,000,000 trillion becquerels (TBq) were released from the fuel during the accident (Table 24.1), dwarfing, by orders of magnitude, radiation released from other highly publicized reactor accidents at Windscale (U.K.) and three-Mile Island (U.S.)3,8 The Chernobyl accident happened while a test was being conducted during a normal scheduled shutdown and is attributed mainly to human error.3

  7. Importance of vesicle release stochasticity in neuro-spike communication.

    PubMed

    Ramezani, Hamideh; Akan, Ozgur B

    2017-07-01

    Aim of this paper is proposing a stochastic model for vesicle release process, a part of neuro-spike communication. Hence, we study biological events occurring in this process and use microphysiological simulations to observe functionality of these events. Since the most important source of variability in vesicle release probability is opening of voltage dependent calcium channels (VDCCs) followed by influx of calcium ions through these channels, we propose a stochastic model for this event, while using a deterministic model for other variability sources. To capture the stochasticity of calcium influx to pre-synaptic neuron in our model, we study its statistics and find that it can be modeled by a distribution defined based on Normal and Logistic distributions.

  8. Reference values and repeatability of the Schirmer tear tests I and II in domesticated, clinically normal dromedary camels (Camelus dromedarius).

    PubMed

    Marzok, Mohamed A; Badawy, Adel M; El-Khodery, Sabry A

    2017-05-01

    To determine the normal values and repeatability for Schirmer tear test (STT) in clinically normal dromedary camels and to analyze the influence of the age and gender on these values. Thirty clinically normal dromedary camels of different ages (calves, immature, and mature). Schirmer tear tests I and II were performed using commercial STT strips. Three measurements were obtained from each eye over three consecutive weeks, and the variance of these measurements was determined. Mean values and coefficient of variation of STT I and STT II for the right and left eyes varied significantly among camel groups (P < 0.05). For STT I, the most frequently recorded values were >14-18, > 22-26, and >30-34 mm/min in calves, immature camels, and mature camels, respectively. For STT II, however, the most frequently recorded values were 7-14, >10-18, and >26-30 mm/min, respectively. The interassay coefficients of variation were 1.7-14.4% and were significantly lower in mature camels than in calves and immature camels (P < 0.05). Age was positively correlated with STT I (r = 0.81) and STT II values (r = 0.88). No significant variations were found between genders. This preliminary study reports STT I and II values and repeatability in normal dromedary camels. This information may assist veterinary practitioners in complete ophthalmic examinations and in accurate diagnosis of ocular surface diseases affecting the tear film in this species. © 2016 American College of Veterinary Ophthalmologists.

  9. Isola spinal instrumentation system for idiopathic scoliosis.

    PubMed

    Benli, I T; Akalin, S; Aydin, E; Baz, A; Citak, M; Kiş, M; Duman, E

    2001-01-01

    Since the definition of three-dimensional components of the scoliotic deformity, there have been important improvements in the surgical treatment of the problem. A derotation maneuver was proposed as a treatment option with CD instrumentation, but the reports of imbalance and decompensation with this system repopularized sublaminar wiring and translation as a corrective maneuver. Isola spinal instrumentation is one of the modern systems that utilizes vertebral translation instead of rod rotation. This study analyzes the results of 24 patients with idiopathic scoliosis who had been followed up for at least 2 years, and were surgically treated with titanium Isola Spinal Instrumentation in the Department of Orthopaedics and Traumatology, Ankara Social Security Hospital. Patients were grouped according to the King-Moe classification. Patients with type III, IV or V curves received only posterior instrumentation while this procedure followed anterior release and discectomy in the same session in patients with type I or II curves. A translation maneuver was utilized in the correction of scoliotic curves using the cantilever technique, either alone or supplemented by sublaminar wiring with Songer multifilament titanium cables. This study aimed to elucidate the effects of this technique in the frontal and sagittal plane curves and the trunk balance. The balance was analyzed clinically and radiologically by measurement of the lateral trunk shift (LT), shift of stable vertebra (SS), and shift of head (SH) in vertebral units (VU). The postoperative correction was significant in the frontal plane for all types of curves (p < 0.05). The postoperative correction was 80.9% +/- 9.5% in type III curves. Overall, the mean Cobb angle of the major curve value in the frontal plane was 66.9 degrees +/- 18.8 degrees, and it was corrected by 62.8% +/- 20.1%. The correction loss of Cobb angles in the frontal plane was 5.4 degrees +/- 5.5 degrees at the last follow-up visit. A normal physiologic thoracic contour (30 degrees - 50 degrees) was achieved in 83.3% of the patients and normal lumbar contour (40 degrees - 60 degrees) in 66.7% of the patients in the sagittal plane. The correction was found to be significant in all balance values (p < 0.05). The postoperative correction in LT values correlated with the correction of the Cobb angle values in the frontal plane. All patients had complete balance (SH: 0 VU and SS: 0 VU) or balanced curves (0 VU < SH, SS < 0.5 VU).Finally, the study concluded that the translation maneuver, especially when used with the cantilever technique, resulted in high correction rates in the frontal plane. Additionally, the technique was also successful in obtaining normal sagittal contours and correcting balance values.

  10. Germination parameterization and development of an after-ripening thermal-time model for primary dormancy release of Lithospermum arvense seeds

    PubMed Central

    Chantre, Guillermo R.; Batlla, Diego; Sabbatini, Mario R.; Orioli, Gustavo

    2009-01-01

    Background and Aims Models based on thermal-time approaches have been a useful tool for characterizing and predicting seed germination and dormancy release in relation to time and temperature. The aims of the present work were to evaluate the relative accuracy of different thermal-time approaches for the description of germination in Lithospermum arvense and to develop an after-ripening thermal-time model for predicting seed dormancy release. Methods Seeds were dry-stored at constant temperatures of 5, 15 or 24 °C for up to 210 d. After different storage periods, batches of 50 seeds were incubated at eight constant temperature regimes of 5, 8, 10, 13, 15, 17, 20 or 25 °C. Experimentally obtained cumulative-germination curves were analysed using a non-linear regression procedure to obtain optimal population thermal parameters for L. arvense. Changes in these parameters were described as a function of after-ripening thermal-time and storage temperature. Key Results The most accurate approach for simulating the thermal-germination response of L. arvense was achieved by assuming a normal distribution of both base and maximum germination temperatures. The results contradict the widely accepted assumption of a single Tb value for the entire seed population. The after-ripening process was characterized by a progressive increase in the mean maximum germination temperature and a reduction in the thermal-time requirements for germination at sub-optimal temperatures. Conclusions The after-ripening thermal-time model developed here gave an acceptable description of the observed field emergence patterns, thus indicating its usefulness as a predictive tool to enhance weed management tactics. PMID:19332426

  11. Survival, recovery and microcystin release of Microcystis aeruginosa in cold or dark condition

    NASA Astrophysics Data System (ADS)

    Ding, Yi; Gan, Nanqin; Liu, Jin; Zheng, Lingling; Li, Lin; Song, Lirong

    2017-03-01

    Microcystis often dominates phytoplankton in eutrophic lakes and must survive a long period of cold or dark conditions. However, the survival strategies of Microcystis to withstand cold or dark stress are less well known. In this study, we conducted experiments on the responses of two toxic Microcystis aeruginosa strains (FACHB-905 and FACHB-915) and their microcystin release in conditions of low temperature (15°C or 4°C, with illumination) or darkness, and subsequent recovery in standard conditions (25°C with illumination). On exposure to 15°C, a small decrease in cell viability was observed, but the cell number increased gradually, suggesting that M. aeruginosa FACHB-905 and FACHB-915 cells seem in general tolerant in 15°C. Interestingly, our results show that a higher carotenoid content and microcystin release potentially enhance the fitness of surviving cells at 15°C. M. aeruginosa cells exposed to lower temperature light stress (4°C) did not completely lose viability and retained the ability to reinitiate growth. In darkness, the maximum quantum yield ( F v/ F m) and the maximum electron transport rate (ETRmax) values and cell viability of M. aeruginosa cells gradually decreased with time. During the recovery period, the photosynthetic efficiency of M. aeruginosa reverted to the normal level. Additionally, M. aeruginosa FACHB-905 and FACHB-915 exposed to low temperature had increased caspase-3-like activity and DNA fragmentation, which suggests the occurrence of a type of cell death in M. aeruginosa cells under cold stress similar to programmed cell death. Overall, our findings could confer certain advantages on the Microcystis for surviving cold or dark conditions encountered in the annual cycle, and help explain its repeated occurrence in water blooms in large and shallow lakes.

  12. Surface rupture and slip distribution of the Denali and Totschunda faults in the 3 November 2002 M 7.9 earthquake, Alaska

    USGS Publications Warehouse

    Haeussler, Peter J.; Schwartz, David P.; Dawson, Timothy E.; Stenner, Heidi D.; Lienkaemper, James J.; Sherrod, Brian; Cinti, Francesca R.; Montone, Paola; Craw, Patricia; Crone, Anthony J.; Personius, Stephen F.

    2004-01-01

    The 3 November 2002 Denali fault, Alaska, earthquake resulted in 341 km of surface rupture on the Susitna Glacier, Denali, and Totschunda faults. The rupture proceeded from west to east and began with a 48-km-long break on the previously unknown Susitna Glacier thrust fault. Slip on this thrust averaged about 4 m (Crone et al., 2004). Next came the principal surface break, along 226 km of the Denali fault, with average right-lateral offsets of 4.5–5.1 m and a maximum offset of 8.8 m near its eastern end. The Denali fault trace is commonly left stepping and north side up. About 99 km of the fault ruptured through glacier ice, where the trace orientation was commonly influenced by local ice fabric. Finally, slip transferred southeastward onto the Totschunda fault and continued for another 66 km where dextral offsets average 1.6–1.8 m. The transition from the Denali fault to the Totschunda fault occurs over a complex 25-km-long transfer zone of right-slip and normal fault traces. Three methods of calculating average surface slip all yield a moment magnitude of Mw 7.8, in very good agreement with the seismologically determined magnitude of M 7.9. A comparison of strong-motion inversions for moment release with our slip distribution shows they have a similar pattern. The locations of the two largest pulses of moment release correlate with the locations of increasing steps in the average values of observed slip. This suggests that slip-distribution data can be used to infer moment release along other active fault traces.

  13. Carbon isotope analyses of n-alkanes released from rapid pyrolysis of oil asphaltenes in a closed system.

    PubMed

    Chen, Shasha; Jia, Wanglu; Peng, Ping'an

    2016-08-15

    Carbon isotope analysis of n-alkanes produced by the pyrolysis of oil asphaltenes is a useful tool for characterizing and correlating oil sources. Low-temperature (320-350°C) pyrolysis lasting 2-3 days is usually employed in such studies. Establishing a rapid pyrolysis method is necessary to reduce the time taken for the pretreatment process in isotope analyses. One asphaltene sample was pyrolyzed in sealed ampoules for different durations (60-120 s) at 610°C. The δ(13) C values of the pyrolysates were determined by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). The molecular characteristics and isotopic signatures of the pyrolysates were investigated for the different pyrolysis durations and compared with results obtained using the normal pyrolysis method, to determine the optimum time interval. Several asphaltene samples derived from various sources were analyzed using this method. The asphaltene pyrolysates of each sample were similar to those obtained by the flash pyrolysis method on similar samples. However, the molecular characteristics of the pyrolysates obtained over durations longer than 90 s showed intensified secondary reactions. The carbon isotopic signatures of individual compounds obtained at pyrolysis durations less than 90 s were consistent with those obtained from typical low-temperature pyrolysis. Several asphaltene samples from various sources released n-alkanes with distinct carbon isotopic signatures. This easy-to-use pyrolysis method, combined with a subsequent purification procedure, can be used to rapidly obtain clean n-alkanes from oil asphaltenes. Carbon isotopic signatures of n-alkanes released from oil asphaltenes from different sources demonstrate the potential application of this method in 'oil-oil' and 'oil-source' correlations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. 3,5-Di-t-butyl catechol is a potent human ryanodine receptor 1 activator, not suitable for the diagnosis of malignant hyperthermia susceptibility.

    PubMed

    Lacava, Caterina; Michalek-Sauberer, Andrea; Kraft, Birgit; Sgaragli, Giampietro; Sipos, Elisabeth; Höller, Carmen; Kress, Hans Georg; Fusi, Fabio; Weigl, Lukas G

    2012-07-01

    3,5-Di-t-butyl catechol (DTCAT) releases Ca(2+) from rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Hence, it is a candidate for use as a substitute for halothane or caffeine in the in vitro contracture test for the diagnosis of susceptibility to malignant hyperthermia (MH). To characterize the effect of DTCAT at cell level, Ca(2+) release experiments were performed on cultured, human skeletal muscle myotubes using the fluorescent Ca(2+) indicator fura2-AM. DTCAT was also assayed in the in vitro contracture test on human skeletal muscle bundles obtained from individuals diagnosed susceptible (MHS), normal (MHN) or equivocal for halothane (MHEH) and compared to the standard test substances caffeine and halothane. DTCAT increased, in a concentration-dependent manner and with a higher efficacy as compared to caffeine, the free, intracellular Ca(2+) levels of cultured MHN and MHS skeletal muscle myotubes. This effect was similar in both types of myotubes and involved the release of Ca(2+) from SR stores as well as Ca(2+)-influx from the extracellular space. Inhibition of ryanodine receptors either with ryanodine or with ruthenium red markedly reduced DTCAT-induced increase in intracellular Ca(2+) concentration while abolishing that induced by caffeine. In MHN skeletal muscle bundles, DTCAT induced contractures with an EC(50) value of 160 ± 91 μM. However, the sensitivity of MHS or MHEH muscles to DTCAT was similar to that of MHN muscles. In conclusion, DTCAT is not suitable for the diagnosis of MH susceptibility due to its failure to discriminate between MHN and MHS muscles. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Internal combustion engine cylinder-to-cylinder balancing with balanced air-fuel ratios

    DOEpatents

    Harris, Ralph E.; Bourn, Gary D.; Smalley, Anthony J.

    2006-01-03

    A method of balancing combustion among cylinders of an internal combustion engine. For each cylinder, a normalized peak firing pressure is calculated as the ratio of its peak firing pressure to its combustion pressure. Each cylinder's normalized peak firing pressure is compared to a target value for normalized peak firing pressure. The fuel flow is adjusted to any cylinder whose normalized peak firing pressure is not substantially equal to the target value.

  16. Normal values of urine total protein- and albumin-to-creatinine ratios in term newborns.

    PubMed

    El Hamel, Chahrazed; Chianea, Thierry; Thon, Séverine; Lepichoux, Anne; Yardin, Catherine; Guigonis, Vincent

    2017-01-01

    It is important to have an accurate assessment of urinary protein when glomerulopathy or kidney injury is suspected. Currently available normal values for the neonate population have limited value, in part because they are based on small populations and obsolete creatinine assays. We have performed a prospective study with the aim to update the normal upper values of the urinary total protein-to-creatinine and albumin-to-creatinine ratios in term newborns. Urine samples were collected from 277 healthy, full-term newborns within the first 48 hours (D0-1) and between 72 and 120 h of life (D3-4). Total protein, albumin, creatinine and osmolality were measured and the upper limit of normal (upper-limit) values determined. At D0-1 and D3-4, the upper-limit values for the total protein-to-creatinine ratio were 1431 and 1205 mg/g (162 and 136 g/mol) and those for the albumin-to-creatinine ratio were 746 and 301 mg/g (84 and 34 g/mol), respectively. The upper-limit values were significantly higher at D0-1 than at D3-4 only for the albumin-to-creatinine ratio. This study determined the upper limit of normal values for urinary total protein-to-creatinine and albumin-to-creatinine ratios in the largest population of newborns studied to date. These values can therefore be considered as the most clinically relevant data currently available for the detection and diagnosis of glomerular injury in daily clinical practice in this population.

  17. Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats

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

    Yu, Yunli, E-mail: chrisyu1255@yahoo.com.cn; Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009; Wang, Xinting, E-mail: wxinting1986@yahoo.com.cn

    Accumulating evidences have showed that gatifloxacin causes dysglycemia in both diabetic and non-diabetic patients. Our preliminary study demonstrated that gatifloxacin stimulated glucagon-like peptide 1 (GLP-1) secretion from intestinal cells. The aim of the study was to investigate the association between gatifloxacin-stimulated GLP-1 release and dysglycemia in both normal and streptozotocin-induced diabetic rats and explore the possible mechanisms. Oral administration of gatifloxacin (100 mg/kg/day and 200 mg/kg/day) for 3 and 12 days led to marked elevation of GLP-1 levels, accompanied by significant decrease in insulin levels and increase in plasma glucose. Similar results were found in normal rats treated with 3-daymore » gatifloxacin. Gatifloxacin-stimulated GLP-1 release was further confirmed in NCI-H716 cells, which was abolished by diazoxide, a K{sub ATP} channel opener. QT-PCR analysis showed that gatifloxacin also upregulated expression of proglucagon and prohormone convertase 3 mRNA. To clarify the contradiction on elevated GLP-1 without insulinotropic effect, effects of GLP-1 and gatifloxacin on insulin release were investigated using INS-1 cells. We found that short exposure (2 h) to GLP-1 stimulated insulin secretion and biosynthesis, whereas long exposure (24 h and 48 h) to high level of GLP-1 inhibited insulin secretion and biosynthesis. Moreover, we also confirmed gatifloxacin acutely stimulated insulin secretion while chronically inhibited insulin biosynthesis. All the results gave an inference that gatifloxacin stimulated over-secretion of GLP-1, in turn, high levels of GLP-1 and gatifloxacin synergistically impaired insulin release, worsening hyperglycemia. -- Highlights: ► Gatifloxacin induced hyperglycemia both in diabetic rats and normal rats. ► Gatifloxacin enhanced GLP-1 secretion but inhibited insulin secretion in rats. ► Long-term exposure to high GLP-1 inhibited insulin secretion and biosynthesis. ► GLP-1 over-secretion may be involved in gatifloxacin-induced hyperglycemia.« less

  18. AMBIENT PARTICULATE MATTER DECREASED IN HUMAN ALVEOLAR MACHROPHAGE CYTOKINE RELEASE

    EPA Science Inventory

    Human exposure to ambient airborne particulate matter (PM) is associated with cardiopulmonary mortality and morbidity, including increased hospitalizations for lung infection. Normal lung immune responses to bacterial infection include alveolar macrophage cytokine production and...

  19. 40 CFR 68.25 - Worst-case release scenario analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... used is based on TNT equivalent methods. (1) For regulated flammable substances that are normally gases... shall be used to determine the distance to the explosion endpoint if the model used is based on TNT...

  20. 40 CFR 68.25 - Worst-case release scenario analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... used is based on TNT equivalent methods. (1) For regulated flammable substances that are normally gases... shall be used to determine the distance to the explosion endpoint if the model used is based on TNT...

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