Community-Level Effects of Excess Total Dissolved Solids Doses Using Model Streams

EPA Science Inventory

Model stream chronic dosing studies (42 days) were conducted with four different total dissolved solids (TDS) recipes. The recipes differed in their relative dominance of major ions. One was made from sodium and calcium chloride salts only. Another was similar to the first, but a...

Study design and early result of a phase I study of SABR for early-stage glottic cancer.

PubMed

Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae

2018-05-14

Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Flavonoids and Tannins from Smilax china L. Rhizome Induce Apoptosis Via Mitochondrial Pathway and MDM2-p53 Signaling in Human Lung Adenocarcinoma Cells.

PubMed

Fu, San; Yang, Yanfang; Liu, Dan; Luo, Yan; Ye, Xiaochuan; Liu, Yanwen; Chen, Xin; Wang, Song; Wu, Hezhen; Wang, Yuhang; Hu, Qiwei; You, Pengtao

2017-01-01

In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed. In addition, the total apoptotic rate induced by total tannins was higher than the rate induced by total flavonoids at the same dose. Cleaved-caspase-3 protein levels in A549 cells after treatment with total flavonoids or total tannins were increased in a dose-dependent manner, followed by the activation of caspase-8 and caspase-9, finally triggering to PARP cleavage. Furthermore, total flavonoids and total tannins increased the expression of Bax, decreased the expression of Bcl-2, and promoted cytochrome [Formula: see text] release. Moreover, MDM2 and p-MDM2 proteins were decreased, while p53 and p-p53 proteins were increased, both in a dose-dependent manner, after A549 treatment with total flavonoids and total tannins. Finally, cleaved-caspase-3 protein levels in the total flavonoids or total tannins-treated H1299 (p53 null) and p53-knockdown A549 cells were increased. Our results indicated that total flavonoids and total tannins from SCR exerted a remarkable effect in reducing A549 growth through their action on mitochondrial pathway and disruption of MDM2-p53 balance. Hence, our findings demonstrated a potential application of total flavonoids and total tannins from SCR in the treatment of human lung adenocarcinoma.

Estimated fluoride doses from toothpastes should be based on total soluble fluoride.

PubMed

Oliveira, Maria José L; Martins, Carolina C; Paiva, Saul M; Tenuta, Livia M A; Cury, Jaime A

2013-11-01

The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride-TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children's toothpaste (n = 78)). The estimated dose (mg F/day/Kg of body weight) of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children's toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p < 0.05), no difference between types of toothpaste was found regarding the ingested dose based on TSF (0.039 ± 0.005 and 0.039 ± 0.005 mg F/day/Kg, respectively; p > 0.05). The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children's toothpaste is used.

Estimated Fluoride Doses from Toothpastes Should be Based on Total Soluble Fluoride

PubMed Central

Oliveira, Maria José L.; Martins, Carolina C.; Paiva, Saul M.; Tenuta, Livia M. A.; Cury, Jaime A.

2013-01-01

The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride—TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children’s toothpaste (n = 78)). The estimated dose (mg F/day/Kg of body weight) of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children’s toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p < 0.05), no difference between types of toothpaste was found regarding the ingested dose based on TSF (0.039 ± 0.005 and 0.039 ± 0.005 mg F/day/Kg, respectively; p > 0.05). The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children’s toothpaste is used. PMID:24189183

Radiation dose-rate meter using an energy-sensitive counter

DOEpatents

Kopp, Manfred K.

1988-01-01

A radiation dose-rate meter is provided which uses an energy-sensitive detector and combines charge quantization and pulse-rate measurement to monitor radiation dose rates. The charge from each detected photon is quantized by level-sensitive comparators so that the resulting total output pulse rate is proportional to the dose-rate.

Phase I dose escalation study of capecitabine and erlotinib concurrent with radiation in locally advanced pancreatic cancer.

PubMed

Jiang, Yixing; Mackley, Heath B; Kimchi, Eric T; Zhu, Junjia; Gusani, Niraj; Kaifi, Jussuf; Staveley-O'Carroll, Kevin F; Belani, Chandra P

2014-07-01

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. The median survival of locally advanced nonoperable disease is approximately 9 months. 5-FU-based chemoradiotherapy has been the standard treatment. However, the survival benefit of this approach is modest. To improve the efficacy of 5-FU-based chemoradiation therapy, we evaluated the safety and feasibility of the combination of capecitabine and erlotinib with radiotherapy in this group of patients. A traditional "3 + 3" dose escalation design was adopted in the study. A total of four dose levels were designed. For safety purpose, a minus I dose level (-I) was also planned. The -I level consisted of capecitabine 600 mg/m² and erlotinib 50 mg daily, and the remaining four dose levels were as follows: level I: capecitabine 600 mg/m² bid (twice daily); level II: 700 mg/m² bid; level III: 825 mg/m² bid; and level IV: 925 mg/m² bid. Erlotinib was administered at 100 mg daily at all dose levels. Erlotinib and capceitabine were given continuously Monday through Friday concurrent with radiotherapy (50.4 Gy in 28 fractions). A total of 18 patients were consented. Fifteen patients were enrolled and completed therapy. No dose-limiting toxicity was observed. The most frequent side effects were lymphopenia, nausea, vomiting, diarrhea, electrolyte imbalances, and skin rashes. The majority of the toxicities were grade 1 and 2. No objective response was observed. The median progression-free survival was 0.59 years (95 % CI 0.31-1.1), and the median overall survival was 1.1 years (95 % CI 0.62-1.59). The combination of capecitabine and erlotinib with radiotherapy in locally advanced pancreatic cancer is well tolerated and feasible at the dose level of capecitabine 925 mg/m² bid and erlotinib 100 mg daily.

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

Warren, J.E.; Klaine, S.J.

The field cricket, Acheta domesticus, was used as a test organism to determine the effects of heavy metal exposure on cellular immunity. Insects were separated by sex and exposed to cadmium chloride or mercuric chloride at concentrations of 0, 2.5, and 5.0 ug/g. Exposures consisted of injecting the chemicals into the hemocoel of each insect on days 0, 2, and 4. Hemolymph was collected on day 7 of the study to determine total hemocyte counts, protein levels, and phenoloxidase activity in individual insects. Cadmium chloride decreased the total number of hemocytes in male crickets at 2.5 and 5.0 ug/g andmore » in female crickets at 5.0 ug/g. Protein levels increased in a dose dependent manner in the males but only slightly increased in the females. Mercuric chloride caused a dose-dependent increase in total hemocytes in both male and female crickets. In addition, mercuric chloride caused a dose-dependent increase in protein levels in males but not females.« less

Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt.

PubMed

Ibrahim, N A; Shalaby, A S; Farag, R S; Elbaroty, G S; Nofal, S M; Hassan, E M

2008-04-15

Flavonoid glycosides, orientin and apigenin 3, 8-di-C-glycosides in addition to, iridoid compound, aucubin were isolated from the ethanolic extract of Vitex agnus-castus fruits. Their structures were identified on the basis of the spectroscopic data. The estrogenic activity of the ethanolic extract in two dose levels 0.6 and 1.2 g kg(-1) per body weight (b.w.) was studied by the vaginal smear, and uterine weight methods for normal and ovariectomized female rats. The extract induced significant increase in the uterine weight of ovariectomized rats at two dose levels comparable to that of control group. The percentages of the total average number of scores were increased significantly too. Significant increases in plasma progesterone and total estrogens levels were shown at the two dose levels when compared to that of control group. On the other side, the extract induced significant reduction in luteinizing and plasma prolactin hormones.

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin’s lymphoma: radiation dose to the testes

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

Hattori, Naoya; Gopal, Ajay K.; Shields, Andrew T.

Purpose: To investigate radiation doses to the testes delivered by a radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. Materials and methods: Testicular uptake and retention of 131I-tositumomab were measured, and testicular absorbed doses were calculated for 67 male patients (54+/-11 years of age) with non-Hodgkin's lymphoma who had undergone myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging studies. In a subset of patients, male sex hormones were measured before and 1 year after the therapy. Results: The absorbed dose to the testes showed considerablemore » variability (range=4.4-70.2 Gy). Pretherapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction [4.6+/-1.8 nmol/l (pre-RIT) vs. 3.8+/-2.9 nmol/l (post-RIT), P<0.05]. Patients receiving higher radiation doses to the testes (>=25 Gy) showed a greater reduction [4.7+/-1.6 nmol/l (pre-RIT) vs. 3.3+/-2.7 nmol/l (post-RIT), P<0.05] compared with patients receiving lower doses (<25 Gy), who showed no significant change in total testosterone levels. Conclusion: The testicular radiation absorbed dose varied highly among individual patients. Finally, patients receiving higher doses to the testes were more likely to show post-RIT suppression of testosterone levels.« less

A strategy for reaching therapeutic salicylate levels in patients with rheumatoid arthritis using standardized dosing regimens.

PubMed

Furst, D E; Blocka, K; Cassell, S; Dromgoole, S; Harris, E R; Hirschberg, J M; Josephson, N; Rupp, P A; Paulus, H E; Trimble, R B

1987-04-01

After one to 2 weeks of 45 mg/kg/day choline magnesium trisalicylate (CMT) in 2 divided doses, 51 of 71 patients with rheumatoid arthritis (72%) had observed steady state serum salicylate concentrations between 150 and 300 mg/l (mean salicylate: 213 +/- 10 mg/l), although 17 later required dose adjustment. CMT dosing was changed in 37 cases by using the formula: dosing rate = total clearance X concentration. The expected and observed concentrations were not different (p = 0.31); thus, this formula can help calculate salicylate dosing changes to bring the serum salicylate level to within the therapeutic range.

A randomized controlled clinical trial investigating the effect of calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress and insulin resistance in pregnant women at risk for pre-eclampsia.

PubMed

Asemi, Z; Samimi, M; Heidarzadeh, Z; Khorrammian, H; Tabassi, Z

2012-05-15

Increased levels of pro-inflammatory factors, markers of oxidative stress and insulin resistance during pregnancy have been associated with the development of pre-eclampsia. There is some evidence to suggest that calcium supplement and aspirin can reduce the risk of the disorder. To our knowledge, no reports are available indicating the effects of consumed calcium supplement plus aspirin on high sensitivity C-reactive protein (hs-CRP), oxidative stress parameters and insulin resistance in pregnant women at risk for pre-eclampsia. This study was designed to investigate the effects of consumed calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress parameters and insulin resistance among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was carried out among 42 pregnant women at risk for pre-eclampsia, primigravida, aged 18-40 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to received either the placebo (n = 22) or calcium supplement plus low-dose aspirin (n = 20) for 9 weeks. Calcium supplement plus low-dose aspirin were containing 500 mg carbonate calcium plus 80 mg aspirin. Fasting blood samples were taken at baseline and after 9 weeks intervention to measure serum hs-CRP, oxidative stress parameters including plasma Total Antioxidant Capacity (TAC) and Total Glutathione (GSH), Fasting Plasma Glucose (FPG), serum insulin and HOMA-IR score. Consumption of calcium supplement plus low-dose aspirin resulted in a significant difference serum hs-CRP levels as compared to the placebo (102.87 vs. 3227.75 ng mL(-1), p = 0.01). Also, mean changes for plasma TAC (68.96 vs. -74.46 mmol L(-1), p = 0.04) and total GSH levels (304.33 vs. -39.33 micromol L(-1), p = 0.03) were significantly different between the two groups. No significant differences were found comparing calcium supplement plus low-dose aspirin and placebo in terms of their effects on FPG, serum insulin levels and HOMA-IR. Within-group differences in the placebo group revealed a significant increase in serum hs-CRP levels (3227.75 ng mL(-1), p = 0.008) and marginally significant increase in plasma total GSH levels (304.33 micromol L(-1), p = 0.07). In conclusion, consumption calcium supplement plus low-dose aspirin during pregnancy for 9 weeks in pregnant women at risk for pre-eclampsia resulted in a significant difference serum hs-CRP and increased levels of plasma TAC and total GSH as compared to the placebo group, but could not affect serum insulin levels and HOMA-IR score.

How Long Can the Hubble Space Telescope Operate Reliably? A Total Dose Perspective

NASA Technical Reports Server (NTRS)

Xapsos, M. A.; Stauffer, C.; Jordan, T.; Poivey, C.; Haskins, D. N.; Lum, G.; Pergosky, A. M.; Smith, D. C.; LaBel, K. A.

2014-01-01

The Hubble Space Telescope has been at the forefront of discoveries in the field of astronomy for more than 20 years. It was the first telescope designed to be serviced in space and the last such servicing mission occurred in May 2009. The question of how much longer this valuable resource can continue to return science data remains. In this paper a detailed analysis of the total dose exposure of electronic parts at the box level is performed using solid angle sectoring/3-dimensional ray trace and Monte Carlo radiation transport simulations. Results are related to parts that have been proposed as possible total dose concerns. The spacecraft subsystem that appears to be at the greatest risk for total dose failure is identified. This is discussed with perspective on the overall lifetime of the spacecraft.

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.

PubMed

Takeoka, Hiroaki; Yamada, Kazuhiko; Azuma, Koichi; Zaizen, Yoshiaki; Yamashita, Fumie; Yoshida, Tsukasa; Naito, Yoshiko; Okayama, Yusuke; Miyamoto, Maki; Hoshino, Tomoaki

2014-05-01

The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer. Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy. A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months). The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

PubMed

Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo

2016-10-01

We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

How Does Patient Radiation Exposure Compare With Low-dose O-arm Versus Fluoroscopy for Pedicle Screw Placement in Idiopathic Scoliosis?

PubMed

Su, Alvin W; McIntosh, Amy L; Schueler, Beth A; Milbrandt, Todd A; Winkler, Jennifer A; Stans, Anthony A; Larson, A Noelle

Intraoperative C-arm fluoroscopy and low-dose O-arm are both reasonable means to assist in screw placement for idiopathic scoliosis surgery. Both using pediatric low-dose O-arm settings and minimizing the number of radiographs during C-arm fluoroscopy guidance decrease patient radiation exposure and its deleterious biological effect that may be associated with cancer risk. We hypothesized that the radiation dose for C-arm-guided fluoroscopy is no less than low-dose O-arm scanning for placement of pedicle screws. A multicenter matched-control cohort study of 28 patients in total was conducted. Fourteen patients who underwent O-arm-guided pedicle screw insertion for spinal fusion surgery in 1 institution were matched to another 14 patients who underwent C-arm fluoroscopy guidance in the other institution in terms of the age of surgery, body weight, and number of imaged spine levels. The total effective dose was compared. A low-dose pediatric protocol was used for all O-arm scans with an effective dose of 0.65 mSv per scan. The effective dose of C-arm fluoroscopy was determined using anthropomorphic phantoms that represented the thoracic and lumbar spine in anteroposterior and lateral views, respectively. The clinical outcome and complications of all patients were documented. The mean total effective dose for the O-arm group was approximately 4 times higher than that of the C-arm group (P<0.0001). The effective dose for the C-arm patients had high variability based on fluoroscopy time and did not correlate with the number of imaged spine levels or body weight. The effective dose of 1 low-dose pediatric O-arm scan approximated 85 seconds of the C-arm fluoroscopy time. All patients had satisfactory clinical outcomes without major complications that required returning to the operating room. Radiation exposure required for O-arm scans can be higher than that required for C-arm fluoroscopy, but it depends on fluoroscopy time. Inclusion of more medical centers and surgeons will better account for the variability of C-arm dose due to distinct patient characteristics, surgeon's preference, and individual institution's protocol. Level III-case-control study.

Clinical radiobiology of stage T2-T3 bladder cancer.

PubMed

Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

2004-09-01

To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which included the treatment-related parameters and other clinical factors, revealed that the hemoglobin level and bladder capacity before RT and T-stage were statistically significant factors determining local control and overall survival. The total radiation dose was of borderline statistical significance for overall survival (p = 0.087), and OTT did not reach statistical significance. The results of our study showed that the treatment outcome after RT for bladder cancer depends mainly on clinical factors: hemoglobin level and bladder capacity before RT, and clinical T stage. An increase in the total radiation dose seemed to be associated with a better treatment outcome. The effect of the OTT was difficult to define, because it was influenced by other prognostic factors.

Impact of single-dose nandrolone decanoate on gonadotropins, blood lipids and HMG CoA reductase in healthy men.

PubMed

Gårevik, N; Börjesson, A; Choong, E; Ekström, L; Lehtihet, M

2016-06-01

The aim was to study the effect and time profile of a single dose of nandrolone decanoate (ND) on gonadotropins, blood lipids and HMG CoA reductase [3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR)] in healthy men. Eleven healthy male participants aged 29-46 years were given a single dose of 150 mg ND as an intramuscular dose of Deca Durabol®, Organon. Blood samples for sex hormones, lipids and HMGCR mRNA analysis were collected prior to ND administration day 0, 4 and 14. A significant suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) was seen after 4 days. Total testosterone and bioavailable testosterone level decreased significantly throughout the observed study period. A small but significant decrease in sexual hormone-binding globulin (SHBG) was seen after 4 days but not after 14 days. Total serum (S)-cholesterol and plasma (P)-apolipoprotein B (ApoB) increased significantly after 14 days. In 80% of the individuals, the HMGCR mRNA level was increased 4 days after the ND administration. Our results show that a single dose of 150 mg ND increases (1) HMGCR mRNA expression, (2) total S-cholesterol and (3) P-ApoB level. The long-term consequences on cardiovascular risk that may appear in users remain to be elucidated. © 2015 Blackwell Verlag GmbH.

Different Doses of Tripterygium Glycosides in the Treatment of Diabetic Nephropathy: Effects on Blood Lipids.

PubMed

Wang, Wei

2018-06-07

The aim of this study was to investigate the therapeutic effect of different doses of tripterygium glycosides (TG) in the treatment of diabetic nephropathy (DN). The effect of TG on blood lipids and safety were also evaluated. Sixty patients with type 2 DN were randomly divided into three groups (n=20 per group): low-dose (30 mg/day TG), double-dose (60 mg/day TG) and control (placebo) groups, all three times daily for 6 months. The levels of triglycerides, total cholesterol, urinary protein, plasma albumin and serum tumour necrosis factor (TNF)-α were compared between the three groups. After treatment, urinary protein and TNF-α level significantly decreased in patients in the treatment groups, compared with the control group. This decrease was significantly larger in the double-dose group than in the low-dose group. However, there was no significant decrease in triglycerides and total cholesterol in the two treatment groups. Furthermore, plasma albumin was lower in the treatment groups than in the control group. The double dose of TG has improved clinical efficacy, compared with the low dose, and the same safety profile. © 2018 The Author(s). Published by S. Karger AG, Basel.

Survey of computed tomography scanners in Taiwan: Dose descriptors, dose guidance levels, and effective doses

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

Tsai, H. Y.; Tung, C. J.; Yu, C. C.

2007-04-15

The IAEA and the ICRP recommended dose guidance levels for the most frequent computed tomography (CT) examinations to promote strategies for the optimization of radiation dose to CT patients. A national survey, including on-site measurements and questionnaires, was conducted in Taiwan in order to establish dose guidance levels and evaluate effective doses for CT. The beam quality and output and the phantom doses were measured for nine representative CT scanners. Questionnaire forms were completed by respondents from facilities of 146 CT scanners out of 285 total scanners. Information on patient, procedure, scanner, and technique for the head and body examinationsmore » was provided. The weighted computed tomography dose index (CTDI{sub w}), the dose length product (DLP), organ doses and effective dose were calculated using measured data, questionnaire information and Monte Carlo simulation results. A cost-effective analysis was applied to derive the dose guidance levels on CTDI{sub w} and DLP for several CT examinations. The mean effective dose{+-}standard deviation distributes from 1.6{+-}0.9 mSv for the routine head examination to 13{+-}11 mSv for the examination of liver, spleen, and pancreas. The surveyed results and the dose guidance levels were provided to the national authorities to develop quality control standards and protocols for CT examinations.« less

INSECTICIDAL AND OXIDATIVE EFFECTS OF AZADIRACHTIN ON THE MODEL ORGANISM Galleria mellonella L. (LEPIDOPTERA: PYRALIDAE).

PubMed

Dere, Beyza; Altuntaş, Hülya; Nurullahoğlu, Z Ulya

2015-07-01

The insecticidal effects, specifically, changes in hemolymph total protein and malondialdehyde (MDA) levels, and antioxidant enzyme activities of azadirachtin (AZA) given to the wax moth, Galleria mellonella L. (Lepidoptera: Pyralidae) larvae via force feeding were investigated. Bioassays showed that the LD50 and LD99 (lethal dose) values of AZA were 2.1 and 4.6 μg/larva, respectively. Experimental analyses were performed with five doses of AZA (0.5, 1, 1.5, 2, and 3 μg/larva). Total protein level in larval hemolymph increased at all AZA doses at 24 h whereas a considerable decrease was observed at 2 and 3 μg/larva doses, and only an increase displayed at 1.5 μg/larva at 72 h. The level of MDA increased at 2 and 3 μg/larva doses at 24 h compared with controls. This trend was also observed at 1.5, 2, and 3 μg/larva doses at 72 h and MDA levels were lower when compared with those of 24 h at all doses except for 1.5 μg/larva dose. Catalase activity decreased at 1, 1.5, and 2 μg/larva doses at 24 h whereas increased at all doses except for 0.5 μg/larva at 72 h compared with controls. AZA led to a decline in superoxide dismutase activity at all experimental doses at 24 and 72 h except for 3 μg/larva doses at 72 h. An increase in glutathione-S-transferase (GST) activity was evident at all AZA doses at 24 h. AZA displayed 68% decline in GST activity at 72 h post treatments when compared to 24 h. Consequently, We infer that the toxicity of AZA extends beyond its known actions in molting processes to redox homeostasis. © 2015 Wiley Periodicals, Inc.

Fast method for in-flight estimation of total dose from protons and electrons using RADE Minstrument on JUICE

NASA Astrophysics Data System (ADS)

Hajdas, Wojtek; Mrigakshi, Alankrita; Xiao, Hualin

2017-04-01

The primary concern of the ESA JUICE mission to Jupiter is the harsh particle radiation environment. Ionizing particles introduce radiation damage by total dose effects, displacement damages or single events effects. Therefore, both the total ionizing dose and the displacement damage equivalent fluence must be assessed to alert spacecraft and its payload as well as to quantify radiation levels for the entire mission lifetime. We present a concept and implementations steps for simplified method used to compute in flight a dose rate and total dose caused by protons. We also provide refinement of the method previously developed for electrons. The dose rates values are given for predefined active volumes located behind layers of materials with known thickness. Both methods are based on the electron and proton flux measurements provided by the Electron and Proton Detectors inside the Radiation Hard Electron Monitor (RADEM) located on-board of JUICE. The trade-off between method accuracy and programming limitations for in-flight computations are discussed. More comprehensive and precise dose rate computations based on detailed analysis of all stack detectors will be made during off-line data processing. It will utilize full spectral unfolding from all RADEM detector subsystems.

Therapeutic effect of high-dose green tea extract on weight reduction: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Chen, I-Ju; Liu, Chia-Yu; Chiu, Jung-Peng; Hsu, Chung-Hua

2016-06-01

To examine the effect and safety of high-dose green tea extract (Epigallocatechin gallate, EGCG) at a daily dosage of 856.8 mg on weight reduction and changes of lipid profile and obesity-related hormone peptides in women with central obesity. We conducted a randomized, double-blind trial registered under ClinicalTrials.gov Identifier no. NCT02147041. A total of 115 women with central obesity were screened at our clinic. 102 of them with a body mass index (BMI) ≥ 27 kg/m(2) and a waist circumference (WC) ≥ 80 cm were eligible for the study. These women were randomly assigned to either a high-dose green tea group or placebo group. The total treatment time was 12 weeks. The main outcome measures were anthropometric measurements, lipid profiles, and obesity related hormone peptides including leptin, adiponectin, ghrelin, and insulin. Significant weight loss, from 76.8 ± 11.3 kg to 75.7 ± 11.5 kg (p = 0.025), as well as decreases in BMI (p = 0.018) and waist circumference (p = 0.023) were observed in the treatment group after 12 weeks of high-dose EGCG treatment. This study also demonstrated a consistent trend of decreased total cholesterol, reaching 5.33%, and decreased LDL plasma levels. There was good tolerance of the treatment among subjects without any side effects or adverse events. Significantly lower ghrelin levels and elevated adiponectin levels were detected in the study group than in the placebo group. 12 weeks of treatment with high-dose green tea extract resulted in significant weight loss, reduced waist circumference, and a consistent decrease in total cholesterol and LDL plasma levels without any side effects or adverse effects in women with central obesity. The antiobestic mechanism of high-dose green tea extract might be associated in part with ghrelin secretion inhibition, leading to increased adiponectin levels. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Assessment of dose rate to terrestrial biota in the area around coal fired power plant applying ERICA tool and RESRAD BIOTA code.

PubMed

Ćujić, Mirjana; Dragović, Snežana

2018-08-01

This paper presents the environmental radiation risk assessment based on two software program approaches ERICA Tool (version 1.2) and RESRAD BIOTA (version 1.5) to estimate dose rates to terrestrial biota in the area around the largest coal fired power plant in Serbia. For dose rate assessment software's default reference animals and plants and the best estimated values of activity concentrations of 238 U, 234 U, 234 Th, 232 Th, 230 Th, 226 Ra, 210 Pb, 210 Po, 137 Cs in soil were used. Both approaches revealed the highest contribution to the internal dose rate due to 226 Ra and 210 Po, while 137 Cs contributed the most to the external dose rate. In the investigated area total dose rate to biota derived using ERICA Tool ranged from 0.3 to 14.4 μGy h -1 . The natural radionuclides exhibited significantly higher contribution to the total dose rate than the artificial one. In the investigated area, only dose rate for lichens and bryophytes exceeded ERICA Tool screening value of total dose rate of 10 μGy h -1 suggested as confident that environmental risks are negligible. The assessed total dose rates for reference animals and plants using RESRAD BIOTA were found to be 7 and 3 μGy h -1 , respectively. In RESRAD BIOTA - Level 3, 10 species (Lumbricus terrestris, Rana lessonae, Sciurus vulgaris, Anas platyrhynchos, Lepus europaeus, Vulpes vulpes, Capreolus capreolus, Suss crofa, Quercu srobur, Tilia spp.) representative for the study area were modeled. Among them the highest total dose rate (4.5 μGy h -1 ) was obtained for large mammals. Differences in the predicted dose rates to biota using the two software programs are the consequence of the difference in the values of transfer parameters used to calculate activity concentrations in biota. Doses of ionizing radiation estimated in this study will not exhibit deterministic effects at the population level. Thus, the obtained results indicate no significant radiation impact of coal fired power plant operation on terrestrial biota. This paper confirms the use ERICA Tool and RESRAD BIOTA softwares as flexible and effective means of radiation impact assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

ELDRS Characterization for a Very High Dose Mission

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

2010-01-01

Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing.

PubMed

Edelman, Alison B; Cherala, Ganesh; Blue, Steven W; Erikson, David W; Jensen, Jeffrey T

2016-07-01

To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations. Healthy, reproductive-age women with obese and normal BMIs received 1.5mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5h. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group. A total of 10 women enrolled and completed the study (normal BMI=5, median 22.8kg/m(2), range 20.8-23.7; obese BMI=5, 39.5kg/m(2), range 35.9-46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern. Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women. This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women. Copyright © 2016 Elsevier Inc. All rights reserved.

Toxicity of dietary Heliotropium circinatum to rats.

PubMed

Eröksüz, H; Eröksüz, Y; Ozer, H; Ceribasi, A O; Tosun, F; Tamer, U; Kizilay, C Akyüz

2003-08-01

Pyrrolizidine alkaloid intoxication was produced in adult, male rats by feeding different levels (0, 1, 3, 5 or 10%) of Heliotropium circinatum for 20 w. Combined GC-MS revealed 0.15% total alkaloid content in the plant material of which 12% and 88% were basic and N-oxide forms, respectively. The specific alkaloids identified were europine (67.33%), heliotrine (16.34%), lasiocarpine (8.12%), heleurine (4.18%), echinatine (1.56%), 7-angeylheliotrine (1.19%), and an unknown alkaloid (1.28%). Neither mortality nor significant clinical changes occurred in test groups. Mild to moderate, dose-related hepatic megalocytosis was the most prominent histopathological finding. In addition to chronic hepatotoxicity, notable medial thickening occurred in the pulmonary arterioles and arteries of the high-dosed groups. This study indicated that H. circinatum plant has limited toxic potential in rats with mild to moderate histological changes and no mortality at the dosing levels, total doses, or time of exposure employed.

SU-E-T-812: Volumetric Modulated Arc Therapy-Total Body Irradiation (VMAT-TBI) V.s. Conventional Extended SSD-TBI (cTBI): A Dosimetric Comparisom

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

Ouyang, L; Folkerts, M; Lee, H

2015-06-15

Purpose: To perform a dosimetric evaluation on a new developed volumetric modulated arc therapy based total body irradiation (VMAT-TBI). Methods: Three patients were CT scanned with an indexed rotatable body frame to get whole body CT images. Concatenated CT images were imported in Pinnacle treatment planning system and whole body and lung were contoured as PTV and organ at risk, respectively. Treatment plans were generated by matching multiple isocenter volumetric modulated arc (VMAT) fields of the upper body and multiple isocenter parallel-opposed fields of the lower body. For each plan, 1200 cGy in 8 fractions was prescribed to the wholemore » body volume and the lung dose was constrained to a mean dose of 750 cGy. Such a two-level dose plan was achieved by inverse planning of the torso VMAT fields. For comparison, conventional standing TBI (cTBI) plans were generated on the same whole body CT images at an extended SSD (550cm).The shape of compensators and lung blocks are simulated using body segments and lung contours Compensation was calculated based on the patient CT images, in mimic of the standing TBI treatment. The whole body dose distribution of cTBI plans were calculated with a home-developed GPU Monte Carlo dose engine. Calculated cTBI dose distribution was prescribed to the mid-body point at umbilical level. Results: The VMAT-TBI treatment plans of three patients’ plans achieved 80.2%±5.0% coverage of the total body volume within ±10% of the prescription dose, while cTBI treatment plans achieved 72.2%±4.0% coverage of the total body volume. The averaged mean lung dose of all three patients is lower for VMAT-TBI (7.48 cGy) than for cTBI (8.96 cGy). Conclusion: The proposed patient comfort-oriented VMAT-TBI technique provides for a uniform dose distribution within the total body while reducing the dose to the lungs.« less

Low-dose CT imaging of a total hip arthroplasty phantom using model-based iterative reconstruction and orthopedic metal artifact reduction.

PubMed

Wellenberg, R H H; Boomsma, M F; van Osch, J A C; Vlassenbroek, A; Milles, J; Edens, M A; Streekstra, G J; Slump, C H; Maas, M

2017-05-01

To compare quantitative measures of image quality, in terms of CT number accuracy, noise, signal-to-noise-ratios (SNRs), and contrast-to-noise ratios (CNRs), at different dose levels with filtered-back-projection (FBP), iterative reconstruction (IR), and model-based iterative reconstruction (MBIR) alone and in combination with orthopedic metal artifact reduction (O-MAR) in a total hip arthroplasty (THA) phantom. Scans were acquired from high- to low-dose (CTDI vol : 40.0, 32.0, 24.0, 16.0, 8.0, and 4.0 mGy) at 120- and 140- kVp. Images were reconstructed using FBP, IR (iDose 4 level 2, 4, and 6) and MBIR (IMR, level 1, 2, and 3) with and without O-MAR. CT number accuracy in Hounsfield Units (HU), noise or standard deviation, SNRs, and CNRs were analyzed. The IMR technique showed lower noise levels (p < 0.01), higher SNRs (p < 0.001) and CNRs (p < 0.001) compared with FBP and iDose 4 in all acquisitions from high- to low-dose with constant CT numbers. O-MAR reduced noise (p < 0.01) and improved SNRs (p < 0.01) and CNRs (p < 0.001) while improving CT number accuracy only at a low dose. At the low dose of 4.0 mGy, IMR level 1, 2, and 3 showed 83%, 89%, and 95% lower noise values, a factor 6.0, 9.2, and 17.9 higher SNRs, and 5.7, 8.8, and 18.2 higher CNRs compared with FBP respectively. Based on quantitative analysis of CT number accuracy, noise values, SNRs, and CNRs, we conclude that the combined use of IMR and O-MAR enables a reduction in radiation dose of 83% compared with FBP and iDose 4 in the CT imaging of a THA phantom.

Occupational exposure due to naturally occurring radionuclide material in granite quarry industry.

PubMed

Ademola, J A

2012-02-01

The potential occupational exposure in granite quarry industry due to the presence of naturally occurring radioactive material (NORM) has been investigated. The activity concentrations of (40)K, (226)Ra and (232)Th were determined using gamma-ray spectroscopy method. The annual effective dose of workers through different exposure pathways was determined by model calculations. The total annual effective dose varied from 21.48 to 33.69 μSv y(-1). Inhalation dose contributes the highest to the total effective dose. The results obtained were much lower than the intervention exemption levels (1.0 mSv y(-1)) given in the International Commission on Radiological Protection Publication 82.

Dose-dependent consumption of farmed Atlantic salmon (Salmo salar) increases plasma phospholipid n-3 fatty acids differentially

PubMed Central

Raatz, Susan K.; Rosenberger, Thad A.; Johnson, LuAnn K.; Wolters, William W.; Burr, Gary S; Picklo, Matthew J.

2013-01-01

Enhanced omega-3 fatty acid (n-3) intake benefits cardiovascular disease (CVD) risk reduction. Increasing consumption at a population level may be better addressed by diet than through supplementation. However, limited data are available on the effect of the dose response to fish intake on plasma levels of n-3 fatty acids. To compare the effects of different doses of farmed Atlantic salmon on plasma phospholipid fatty acid (PLFA) proportions and CVD risk biomarkers (glucose, insulin, HOMAIR, hsCRP, and IL-6) in healthy subjects we performed a randomized 3-period cross-over designed trial (4 wk treatment, 4-8 wk washout) to compare the effects of twice/wk consumption of farmed Atlantic salmon at doses of 90, 180, and 270 g in 19 apparently healthy men and women with a mean age of aged 40-65 years and a BMI between 25-34.9 kg/m2. All study visits were conducted at the USDA, ARS Grand Forks Human Nutrition Research Center. EPA and total n-3 were increased (p<0.05) by all treatments in a dose response manner, with total n-3 of 8.03 ± 0.26 and 9.21 ± 0.26 % for 180 and 270 g doses, respectively. Linoleic acid did not change in response to treatment while arachidonic acid (P<0.05) and total omega-6 fatty acids (n-6) decreased dose dependently (<0.0001). The addition of farmed Atlantic salmon to the diet twice/wk for 4 wk at portions of 180g and 270g modifies PLFA proportions of n-3 and n-6 in a level associated with decreased risk for CVD. PMID:23351633

Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid.

PubMed

Cisneros, F J; Gough, B J; Patton, R E; Ferguson, S A

2005-01-01

Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximately 90% of the control and total protein levels to approximately 93% of the control while substantially elevating triglyceride levels to approximately 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximately 62% higher than the controls and total protein levels were approximately 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same-sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints. Copyright (c) 2005 John Wiley & Sons, Ltd.

SU-G-BRB-14: Uncertainty of Radiochromic Film Based Relative Dose Measurements

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

Devic, S; Tomic, N; DeBlois, F

2016-06-15

Purpose: Due to inherently non-linear dose response, measurement of relative dose distribution with radiochromic film requires measurement of absolute dose using a calibration curve following previously established reference dosimetry protocol. On the other hand, a functional form that converts the inherently non-linear dose response curve of the radiochromic film dosimetry system into linear one has been proposed recently [Devic et al, Med. Phys. 39 4850–4857 (2012)]. However, there is a question what would be the uncertainty of such measured relative dose. Methods: If the relative dose distribution is determined going through the reference dosimetry system (conversion of the response bymore » using calibration curve into absolute dose) the total uncertainty of such determined relative dose will be calculated by summing in quadrature total uncertainties of doses measured at a given and at the reference point. On the other hand, if the relative dose is determined using linearization method, the new response variable is calculated as ζ=a(netOD)n/ln(netOD). In this case, the total uncertainty in relative dose will be calculated by summing in quadrature uncertainties for a new response function (σζ) for a given and the reference point. Results: Except at very low doses, where the measurement uncertainty dominates, the total relative dose uncertainty is less than 1% for the linear response method as compared to almost 2% uncertainty level for the reference dosimetry method. The result is not surprising having in mind that the total uncertainty of the reference dose method is dominated by the fitting uncertainty, which is mitigated in the case of linearization method. Conclusion: Linearization of the radiochromic film dose response provides a convenient and a more precise method for relative dose measurements as it does not require reference dosimetry and creation of calibration curve. However, the linearity of the newly introduced function must be verified. Dave Lewis is inventor and runs a consulting company for radiochromic films.« less

Intraoperative radiation exposure in spinal scoliosis surgery for pediatric patients using the O-arm® imaging system.

PubMed

Kobayashi, Kazuyoshi; Ando, Kei; Ito, Kenyu; Tsushima, Mikito; Morozumi, Masayoshi; Tanaka, Satoshi; Machino, Masaaki; Ota, Kyotaro; Ishiguro, Naoki; Imagama, Shiro

2018-05-01

The O-arm ® navigation system allows intraoperative CT imaging that can facilitate highly accurate instrumentation surgery, but radiation exposure is higher than with X-ray radiography. This is a particular concern in pediatric surgery. The purpose of this study is to examine intraoperative radiation exposure in pediatric spinal scoliosis surgery using O-arm. The subjects were 38 consecutive patients (mean age 12.9 years, range 10-17) with scoliosis who underwent spinal surgery with posterior instrumentation using O-arm. The mean number of fused vertebral levels was 11.0 (6-15). O-arm was performed before and after screw insertion, using an original protocol for the cervical, thoracic, and lumbar spine doses. The average scanning range was 6.9 (5-9) intervertebral levels per scan, with 2-7 scans per patient (mean 4.0 scans). Using O-arm, the dose per scan was 92.5 (44-130) mGy, and the mean total dose was 401 (170-826) mGy. This dose was 80.2% of the mean preoperative CT dose of 460 (231-736) mGy (P = 0.11). The total exposure dose and number of scans using intraoperative O-arm correlated strongly and significantly with the number of fused levels; however, there was no correlation with the patient's height. As the fused range became wider, several scans were required for O-arm, and the total radiation exposure became roughly the same as that in preoperative CT. Use of O-arm in our original protocol can contribute to reduction in radiation exposure.

Effects of sublethal fenitrothion ingestion on cholinesterase inhibition, standard metabolism, thermal preference, and prey-capture ability in the Australian central bearded dragon (Pogona vitticeps, Agamidae).

PubMed

Bain, David; Buttemer, William A; Astheimer, Lee; Fildes, Karen; Hooper, Michael J

2004-01-01

The central bearded dragon (Pogona vitticeps) is a medium-sized lizard that is common in semiarid habitats in Australia and that potentially is at risk of fenitrothion exposure from use of the chemical in plague locust control. We examined the effects of single sublethal doses of this organophosphate (OP; low dose = 2.0 mg/kg; high dose = 20 mg/kg; control = vehicle alone) on lizard thermal preference, standard metabolic rate, and prey-capture ability. We also measured activities of plasma total cholinesterase (ChE) and acetylcholinesterase before and at 0, 2, 8, 24, 120, and 504 h after OP dosing. Predose plasma total ChE activity differed significantly between sexes and averaged 0.66 +/- 0.06 and 0.45 +/- 0.06 micromol/min/ml for males and females, respectively. Approximately 75% of total ChE activity was attributable to butyrylcholinesterase. Peak ChE inhibition reached 19% 2 h after OP ingestion in the low-dose group, and 68% 8 h after ingestion in high-dose animals. Neither OP doses significantly affected diurnal body temperature, standard metabolic rate, or feeding rate. Plasma total ChE levels remained substantially depressed up to 21 d after dosing in the high-dose group, making this species a useful long-term biomonitor of OP exposure in its habitat.

[Protective effect of emodin pretreatment in young rats with intrahepatic cholestasis].

PubMed

Xiong, Xiao-Li; Yan, Su-Qi; Qin, Huan; Zhou, Li-Shan; Zhang, Ling-Ling; Jiang, Zhi-Xia; Ding, Yan

2016-02-01

To investigate the protective effect of emodin in young rats with intrahepatic cholestasis. A total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate (ANIT, 50 mg/kg) was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points. Compared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points (P<0.01). In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours (P<0.05). At 24, 48, and 72 hours, the high-, medium-, and low-dose emodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group (P<0.05); the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group (P<0.05). The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain improvement in pathological changes of the liver at each time point, and the medium-dose emodin group had better improvement compared with the high- and low-dose emodin groups. Emodin can effectively improve ANIT-induced intrahepatic cholestasis in young rats, and medium-dose emodin shows the best effect.

The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children.

PubMed

Gnatzy, Richard; Hempel, Gunther; Kaisers, Udo X; Höhne, Claudia

2015-11-01

The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, p<0.05. A total of 62 children (11.5±2.9 years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

RCT: Module 2.06, Air Sampling Program and Methods, Course 8772

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

Hillmer, Kurt T.

The inhalation of radioactive particles is the largest cause of an internal radiation dose. Airborne radioactivity measurements are necessary to ensure that the control measures are and continue to be effective. Regulations govern the allowable effective dose equivalent to an individual. The effective dose equivalent is determined by combining the external and internal dose equivalent values. Typically, airborne radioactivity levels are maintained well below allowable levels to keep the total effective dose equivalent small. This course will prepare the student with the skills necessary for RCT qualification by passing quizzes, tests, and the RCT Comprehensive Phase 1, Unit 2 Examinationmore » (TEST 27566) and will provide in-the-field skills.« less

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

PubMed

Jung, Caroline; Greco, Santo; Nguyen, Hanh H T; Ho, Jui T; Lewis, John G; Torpy, David J; Inder, Warrick J

2014-11-26

Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period. An oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

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

Farfan, E.; Jannik, T.

This article describes major studies performed by the Chernobyl Center's International Radioecology Laboratory (Slavutich, Ukraine) on radioecology of murine rodents and shrews inhabiting the Chernobyl Exclusion Zone. The article addresses the long-term (1986-2005) and seasonal dynamics of radioactive contamination of animals, and reviews interspecies differences in radionuclide accumulations and factors affecting the radionuclide accumulations. It is shown that bioavailability of radionuclides in the 'soil-to-plant' chain and a trophic specialization of animals play key roles in determining their actual contamination levels. The total absorbed dose rates in small mammals significantly reduced during the years following the Chernobyl Nuclear Power Plant accident.more » In 1986, the absorbed dose rate reached 1.3-6.0 Gy hr{sup -1} in the central areas of the Chernobyl Exclusion Zone (the 'Red Forest'). In 1988 and 1990, the total absorbed dose rates were 1.3 and 0.42 Gy hr{sup -1}, respectively. In 1995, 2000, and 2005, according to the present study, the total absorbed dose rates rarely exceeded 0.00023, 0.00018, and 0.00015 Gy hr{sup -1}, respectively. Contributions of individual radiation sources into the total absorbed dose are described.« less

Controlled-release systemic delivery - a new concept in cancer chemoprevention

PubMed Central

2012-01-01

Many chemopreventive agents have encountered bioavailability issues in pre-clinical/clinical studies despite high oral doses. We report here a new concept utilizing polycaprolactone implants embedded with test compounds to obtain controlled systemic delivery, circumventing oral bioavailability issues and reducing the total administered dose. Compounds were released from the implants in vitro dose dependently and for long durations (months), which correlated with in vivo release. Polymeric implants of curcumin significantly inhibited tissue DNA adducts following the treatment of rats with benzo[a]pyrene, with the total administered dose being substantially lower than typical oral doses. A comparison of bioavailability of curcumin given by implants showed significantly higher levels of curcumin in the plasma, liver and brain 30 days after treatment compared with the dietary route. Withaferin A implants resulted in a nearly 60% inhibition of lung cancer A549 cell xenografts, but no inhibition occurred when the same total dose was administered intraperitoneally. More than 15 phytochemicals have been tested successfully by this formulation. Together, our data indicate that this novel implant-delivery system circumvents oral bioavailability issues, provides continuous delivery for long durations and lowers the total administered dose, eliciting both chemopreventive/chemotherapeutic activities. This would also allow the assessment of activity of minor constituents and synthetic metabolites, which otherwise remain uninvestigated in vivo. PMID:22696595

A randomized, double-blind, placebo-controlled clinical trial on the treatment of vitamin D insufficiency in postmenopausal women

PubMed Central

Hansen, Karen E.; Johnson, R. Erin; Chambers, Kaitlin R.; Johnson, Michael G.; Lemon, Christina C.; Thuy Vo, Tien Nguyen; Marvdashti, Sheeva

2015-01-01

Importance Experts debate optimal 25(OH)D levels for musculoskeletal health. Objective To compare effects of placebo, low-dose and high-dose vitamin D on one-year changes in total fractional calcium absorption, bone mineral density, Timed-Up-and-Go and 5-sit-to-stand tests and muscle mass in postmenopausal women with vitamin D insufficiency. Design Randomized, double-blind, placebo-controlled, clinical trial conducted from May 2010 to August 2014. Setting Single-center trial conducted in Madison, Wisconsin. Participants 230 postmenopausal women ≤75 years old with baseline 25(OH)D levels 14-27 ng/mL and no osteoporosis. Intervention Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=76), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels ≥30 ng/mL. Main Outcome Measures One year change in total fractional calcium absorption using two stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed-Up-and-Go and 5-Sit-to-Stand tests, functional status (Health Assessment Questionnaire) and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of p-values to control the false discovery rate. Results After controlling for baseline absorption, calcium absorption increased 1% (10 mg/day) in the high-dose arm, but decreased by 2% in low-dose (p=0.005 vs. high-dose) and by 1.3% placebo (p=0.03 vs. high-dose) arms. We found no between-arm changes in spine, mean total hip, mean femoral neck or total body bone mineral density, trabecular bone score, muscle mass, 5-sit-to-stand or Timed-Up-and-Go test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity or functional status. Conclusion and Relevance High-dose vitamin D therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on bone mineral density, muscle function, muscle mass or falls. We found no data to support experts’ recommendations to maintain serum 25(OH)D levels ≥30 ng/mL in postmenopausal women. Instead, we found that low and high-dose vitamin D were equivalent to placebo, in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels <30 ng/mL. ClinicalTrials.gov.Identifier:NCT00933244 PMID:26237520

Caffeine and sleep-deprivation mediated changes in open-field behaviours, stress response and antioxidant status in mice.

PubMed

Onaolapo, J Olakunle; Onaolapo, Y Adejoke; Akanmu, A Moses; Olayiwola, Gbola

2016-01-01

Effects of daily caffeine consumption on open-field behaviours, serum corticosterone and brain antioxidant levels were investigated after six hours of total sleep-deprivation in prepubertal mice. We tested the hypothesis that daily caffeine consumption may significantly alter behaviour, stress and antioxidative response of prepubertal mice to an acute episode of total sleep-deprivation. Prepubertal Swiss mice of both sexes were assigned to two main groups of 120 each (subdivided into 6 groups of 10 each, based on sex), and administered vehicle or graded oral doses of caffeine (10, 20, 40, 80 and 120 mg/kg/day) for 14 days. On day 14, a main group was subjected to 6 h of total sleep-deprivation by 'gentle-handling'. Open-field behaviours were then assessed in both groups, after which animals were euthanized, and levels of corticosterone, superoxide dismutase and glutathione peroxidase assayed. Horizontal locomotion, rearing and grooming increased significantly, compared to control, with sleep-deprived (SD) mice showing stronger caffeine-driven responses at higher doses; and SD female mice showing sustained response to caffeine, compared to respective males. Plasma corticosterone increased with increasing doses of caffeine in both non sleep-deprived (NSD) and SD mice; although SD mice had higher corticosterone levels. Sleep-deprivation and/or higher doses of caffeine were associated with derangements in brain antioxidant levels. Repeated caffeine consumption and/or acute sleep-deprivation led to significant changes in pattern of open-field behaviour and stress/antioxidant response in mice. Responses seen in the study are probably due to modulatory effects of caffeine on the total body response to stressful stimuli.

TH-A-19A-06: Site-Specific Comparison of Analytical and Monte Carlo Based Dose Calculations

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

Schuemann, J; Grassberger, C; Paganetti, H

2014-06-15

Purpose: To investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict dose distributions and to verify currently used uncertainty margins in proton therapy. Methods: Dose distributions predicted by an analytical pencilbeam algorithm were compared with Monte Carlo simulations (MCS) using TOPAS. 79 complete patient treatment plans were investigated for 7 disease sites (liver, prostate, breast, medulloblastoma spine and whole brain, lung and head and neck). A total of 508 individual passively scattered treatment fields were analyzed for field specific properties. Comparisons based on target coverage indices (EUD, D95, D90 and D50)more » were performed. Range differences were estimated for the distal position of the 90% dose level (R90) and the 50% dose level (R50). Two-dimensional distal dose surfaces were calculated and the root mean square differences (RMSD), average range difference (ARD) and average distal dose degradation (ADD), the distance between the distal position of the 80% and 20% dose levels (R80- R20), were analyzed. Results: We found target coverage indices calculated by TOPAS to generally be around 1–2% lower than predicted by the analytical algorithm. Differences in R90 predicted by TOPAS and the planning system can be larger than currently applied range margins in proton therapy for small regions distal to the target volume. We estimate new site-specific range margins (R90) for analytical dose calculations considering total range uncertainties and uncertainties from dose calculation alone based on the RMSD. Our results demonstrate that a reduction of currently used uncertainty margins is feasible for liver, prostate and whole brain fields even without introducing MC dose calculations. Conclusion: Analytical dose calculation algorithms predict dose distributions within clinical limits for more homogeneous patients sites (liver, prostate, whole brain). However, we recommend treatment plan verification using Monte Carlo simulations for patients with complex geometries.« less

Ameliorative effects of curcumin on the spermatozoon tail length, count, motility and testosterone serum level in metronidazole-treated mice.

PubMed

Karbalay-Doust, S; Noorafshan, A

2011-01-01

Metronidazole (MTZ) is used as an antiparasitic drug. Curcumin is considered as anti-oxidant and anti-inflammatory agent. The ameliorative effects of curcumin on MTZ induced toxicity on mice spermatozoon tail length, count, motility and testosterone level were investigated. MTZ was administered in 500 and 165 (high and therapeutic doses) mg/kg/day, with and without curcumin (100 mg/kg/day). After 16 days the above parameters were assessed. Spermatozoon count and motility and serum testosterone level MTZ-treated (500 and 165) mice were reduced. In the mice treated with MTZ+curcumin these parameters decreased but in a lesser extent than the MTZ-treated animals. Mid-piece and total lengths of the spermatozoon tail in control animals were 31.6 ± 9.0 μm and 100.3 ± 15.0 μm and in the mice treated with high doses (500) of MTZ were reduced. The mid-piece and total spermatozoon tail length has been decreased in a lesser extent in the mice treated with high dose MTZ+curcumin than the mice treated with high dose MTZ (p<0.01). But the length was not changed in animals treated with therapeutic dose of MTZ. It means curcumin treated animals had ~52% and ~39% average increase in mid-piece and total lengths in comparison with the MTZ-treated (500) animals. Stereological estimation of the sperm tail length, including sampling of spermatozoa and also counting of the intersections of their tails with the stereological grids was a rapid technique and took only 5-10 minutes. It can be concluded that curcumin has an ameliorative effect on the spermatozoon, testosterone level and tail length in MTZ-treated mice.

Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

PubMed

Lemburg, Stefan P; Peters, Soeren A; Roggenland, Daniela; Nicolas, Volkmar; Heyer, Christoph M

2010-12-01

The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p < 0.001) mainly owing to the significantly higher CT-related cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p < 0.001). Overall, CT accounted for 86% of the total cumulative effective dose. Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

PubMed

Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

1998-06-01

Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60. The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule.

Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats.

PubMed

Aziza, Samy Ali Hussein; Azab, Mohammed El-Said; El-Shall, Soheir Kamal

2014-08-01

Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against IOL-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg kg(-1) b.wt.) as one dose every two days, by intraperitoneal injections (IP) and administrated rutin (50 mg kg(-1) b.wt.) as one daily oral dose until the sacrificed day. Blood samples for serum separation and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profiles total iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), transferrin (Tf) and Transferrin Saturation% (TS%)}, ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, total iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), Nitric Oxide (NO) and Total Nucleic Acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that, iron overload (IOL) resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels and AST and ALT activities and also increased liver iron, L-MDA and NO levels. Meanwhile, it decreased serum UIBC, total cholesterol, triacylglycerols, albumin, total protein and liver GSH, TNA levels and Gpx, CAT and SOD activities when compared with the control group. Rutin administration to iron-overloaded rats resulted in significant decrease in serum total iron, TIBC, Tf, TS%, ferritin levels and AST and ALT activities and liver total iron, L-MDA and NO levels with significant increases in serum UIBC, albumin, total protein and total cholesterol levels and in liver GSH, CAT and SOD activities compared with the IOL group. This study provides in vivo evidence that rutin administration can improve the antioxidant defense systems against IOL-induced hepatic oxidative stress in rats. This protective effect in liver of iron-loaded rats may be due to both antioxidant and metal chelation activities.

Carbohydrate-to-insulin ratio is estimated from 300-400 divided by total daily insulin dose in type 1 diabetes patients who use the insulin pump.

PubMed

Kuroda, Akio; Yasuda, Tetsuyuki; Takahara, Mitsuyoshi; Sakamoto, Fumie; Kasami, Ryuichi; Miyashita, Kazuyuki; Yoshida, Sumiko; Kondo, Eri; Aihara, Ken-ichi; Endo, Itsuro; Matsuoka, Taka-aki; Kaneto, Hideaki; Matsumoto, Toshio; Shimomura, Iichiro; Matsuhisa, Munehide

2012-11-01

To optimize insulin dose using insulin pump, basal and bolus insulin doses are widely calculated from total daily insulin dose (TDD). It is recommended that total daily basal insulin dose (TBD) is 50% of TDD and that the carbohydrate-to-insulin ratio (CIR) equals 500 divided by TDD. We recently reported that basal insulin requirement is approximately 30% of TDD. We therefore investigated CIR after adjustment of the proper basal insulin rate. Forty-five Japanese patients with type 1 diabetes were investigated during several weeks of hospitalization. The patients were served standard diabetes meals (25-30 kcal/kg of ideal body weight). Each meal omission was done to confirm basal insulin rate. Target blood glucose level was set at 100 and 150 mg/dL before and 2 h after each meal, respectively. After the basal insulin rate was fixed and target blood glucose levels were achieved, TBD, CIR, TDD, and their products were determined. Mean (±SD) blood glucose levels before and 2 h after meals were 121±47 and 150±61 mg/dL, respectively. TDD was 31.5±9.0 U, and TBD was 27.0±6.5% of TDD. CIR×TDD of breakfast was significantly lower than those of lunch and supper (288±73 vs. 408±92 and 387±83, respectively; P<0.01). CIR has diurnal variance and is estimated from the formula CIR=300/TDD at breakfast or CIR=400/TDD at lunch and supper in type 1 diabetes patients. These results indicate that the insulin dose has been underestimated by using previously established calculations.

Oral MSG administration alters hepatic expression of genes for lipid and nitrogen metabolism in suckling piglets.

PubMed

Chen, Gang; Zhang, Jun; Zhang, Yuzhe; Liao, Peng; Li, Tiejun; Chen, Lixiang; Yin, Yulong; Wang, Jinquan; Wu, Guoyao

2014-01-01

This experiment was conducted to investigate the effects of oral administration of monosodium glutamate (MSG) on expression of genes for hepatic lipid and nitrogen metabolism in piglets. A total of 24 newborn pigs were assigned randomly into one of four treatments (n = 6/group). The doses of oral MSG administration, given at 8:00 and 18:00 to sow-reared piglets between 0 and 21 days of age, were 0 (control), 0.06 (low dose), 0.5 (intermediate dose), and 1 (high dose) g/kg body weight/day. At the end of the 3-week treatment, serum concentrations of total protein and high-density lipoprotein cholesterol in the intermediate dose group were elevated than those in the control group (P < 0.05). Hepatic mRNA levels for fatty acid synthase, acetyl-coA carboxylase, insulin-like growth factor-1, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase were higher in the middle-dose group (P < 0.05), compared with the control group. MSG administration did not affect hepatic mRNA levels for hormone-sensitive lipase or carnitine palmitoyl transferase-1. We conclude that oral MSG administration alters hepatic expression of certain genes for lipid and nitrogen metabolism in suckling piglets.

Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study.

PubMed

Peechakara, Seenia; Bena, James; Clarke, Nigel J; McPhaul, Michael J; Reitz, Richard E; Weil, Robert J; Recinos, Pablo; Kennedy, Laurence; Hamrahian, Amir H

2017-09-01

The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard. The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12). All tests were done in random order. Sensitivity and specificity were calculated for total cortisol and serum free cortisol cut-off levels during cosyntropin stimulation tests. The median (range) age and F/M sex ratios for patients and controls were 54 years (23-62), 2/8, and 33 years (21-51), 6/6, respectively. The best total cortisol cut-off during low dose cosyntropin test, medium dose cosyntropin test, 30 min and 60 min standard dose cosyntropin test were 14.6 μg/dL (100% sensitivity & specificity), 18.7 μg/dL (100% sensitivity, 88% specificity), 16.1 (100% sensitivity & specificity), and 19.5 μg/dL (100% sensitivity & specificity), respectively. There was no difference in the ROC curve for cortisol values between the cosyntropin stimulation tests (p  > 0.41). Using a cortisol cut-off of 18 μg/dL during cosyntropin stimulation tests, only cortisol level at 30 min during standard dose cosyntropin test provided discrimination similar to insulin tolerance test. The best peak free cortisol cut-off levels were 1 μg/dL for insulin tolerance test, 0.9 μg/dL for low dose cosyntropin test, 0.9 μg/dL for medium dose cosyntropin test, and 0.9 μg/dL and 1.3 μg/dL for 30 min and 60 min standard dose cosyntropin test, respectively. All cosyntropin stimulation tests had excellent correlations with insulin tolerance test, when appropriate cut-offs were used. This pilot study does not suggest an advantage in using 25 μg cosyntropin dose during the cosyntropin stimulation test. A serum free cortisol cut-off of 0.9 μg/dL may be used as pass criterion during low dose cosyntropin test, standard dose cosyntropin test cosyntropin test, and 30 min standard dose cosyntropin test.

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.

PubMed

Huang, Zhenhua; Liang, Lining; Li, Lingyu; Xu, Miao; Li, Xiang; Sun, Hao; He, Songwei; Lin, Lilong; Zhang, Yixin; Song, Yancheng; Yang, Man; Luo, Yuling; Loh, Horace H; Law, Ping-Yee; Zheng, Dayong; Zheng, Hui

2016-03-08

Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5-8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer.

Effects of whole-body, ionizing radiation on the semen in beagle dogs

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

Day, P.A.

1988-01-01

Six beagle dogs were exposed to a total dose of 183 R of gamma radiation at a dose rate of 1 R/day, while three other dogs were exposed to a single dose of 100 R. Weekly semen analysis was performed on all irradiated dogs plus four nonirradiated dogs. Semen volume, sperm concentration, total sperm count, sperm motility and sperm head morphometry were examined. Dogs exposed to chronic radiation showed a severe decline in sperm numbers, detected after seven weeks of exposure. Sperm concentration and total sperm count were the first parameters affected and were the only parameters consistently affected. Themore » dogs exposed to 100 R as a single dose, did not show a significant decline in sperm numbers. During a 36 week recovery period, the chronically irradiated dogs did show a slight increase in sperm numbers, but they never approached pre-exposure levels.« less

Switching to instant black coffee modulates sodium selenite-induced cataract in rats.

PubMed

El Okda, E A; Mohamed, M M; Shaheed, E B; Abdel-Moemin, A R

2016-01-01

The influence of daily consumption of some common beverages on the development of cataract in rats was investigated. Total phenol content was determined in the beverages and an oral standardized dose of total phenols from each beverage was given to the treated rats. Weaned male albino rats were used and divided into five groups (n=7). Rats were fed Ain 93G and administered the standardized dose of instant coffee, black tea and hibiscus beverages for 30 days. On day 14 all rats were injected with a single dose of sodium selenite (Na2SeO3) 15 µmol/kg bodyweight, except the control groups NC (negative control, did not receive Na2SeO3) and PC (positive control, was already injected on day 1 of the study). The rats were continued on Ain 93G and the standardized dose for another 16 days. Positive control rats were used. Total phenols were 210, 40, and 44 mg/g dry weight gallic acid equivalent in black coffee, black tea, and hibiscus, respectively. Decreased levels (statistically significant P<0.05) of malondialdehyde, total nitric oxide, Ca-ATPase, tumor necrosis factor-α, interleukin-1β, superoxide dismutase, and conversely, increased levels (statistically significant P<0.05) of total protein, reduced glutathione, catalase were found in the lenses of the coffee group compared to PC. There are co-phenol substances in the instant black coffee that promoted coffee to be the most effective beverage.

Switching to instant black coffee modulates sodium selenite-induced cataract in rats

PubMed Central

El Okda, E. A.; Mohamed, M. M.; Shaheed, E. B.; Abdel-Moemin, A. R.

2016-01-01

The influence of daily consumption of some common beverages on the development of cataract in rats was investigated. Total phenol content was determined in the beverages and an oral standardized dose of total phenols from each beverage was given to the treated rats. Weaned male albino rats were used and divided into five groups (n=7). Rats were fed Ain 93G and administered the standardized dose of instant coffee, black tea and hibiscus beverages for 30 days. On day 14 all rats were injected with a single dose of sodium selenite (Na2SeO3) 15 µmol/kg bodyweight, except the control groups NC (negative control, did not receive Na2SeO3) and PC (positive control, was already injected on day 1 of the study). The rats were continued on Ain 93G and the standardized dose for another 16 days. Positive control rats were used. Total phenols were 210, 40, and 44 mg/g dry weight gallic acid equivalent in black coffee, black tea, and hibiscus, respectively. Decreased levels (statistically significant P<0.05) of malondialdehyde, total nitric oxide, Ca-ATPase, tumor necrosis factor-α, interleukin-1β, superoxide dismutase, and conversely, increased levels (statistically significant P<0.05) of total protein, reduced glutathione, catalase were found in the lenses of the coffee group compared to PC. There are co-phenol substances in the instant black coffee that promoted coffee to be the most effective beverage. PMID:27158251

Long-term variations of the UV-B radiation over Central Europe since early 1960s, as revealed from the UV observations and reconstructed data

NASA Astrophysics Data System (ADS)

Krzyscin, J. W.

2003-04-01

A method of reconstruction of the UV variations for periods when UV-B measurements were not carried out is proposed. The reconstruction is based on observations of total (Sun+sky) radiation by a pyranometer, Dobson total ozone, sunshine duriation from the Campbel Stokes heliograph, and atmospheric column water content taken from NCEP/NOAA reanalysis. Modeled all-sky erythemaly weighted daily dose is calculated as a product of the cloud reduction factor (CRF) over UV range and clear-sky dose from a radiative transfer model. CRF over UV range is estimated from measured CRF for total solar radiation and the statistical dependence relating CRF over UV with that over whole solar spectrum. The measured daily UV doses and daily sum of total radiation taken at Belsk, Poland (52N, 21E) for the period 1976-2001 have been used to construct the regressions for various solar zenith angles. The time series of monthly means from the modeled daily UV doses follows the observed monthly means supporting the possibility of reconstruction of the UV time series for other periods. An inspection of the long-term stability of total radiation measurements is necessary to discuss trends in the reconstructed time series. We examine the data homogeneity analyzing the ratio of the observed to modeled total radiation for fully clear sky days that are selected from the daily values of sunshine duration measured by the Campbel-Stokes heliograph. Combining reconstructed and observed monthly means of the UV doses we found a positive trend in the UV radiation in the period 1980-1995 and almost constant UV level for other periods (early 60s up to 1980, and 1995-2001). The trend pattern suggests dominating role of the long-term total ozone forcing on the UV level with a small impact of the long-term changes in the cloud/aerosol properties.

Radiation dose to the global flying population.

PubMed

Alvarez, Luis E; Eastham, Sebastian D; Barrett, Steven R H

2016-03-01

Civil airliner passengers and crew are exposed to elevated levels of radiation relative to being at sea level. Previous studies have assessed the radiation dose received in particular cases or for cohort studies. Here we present the first estimate of the total radiation dose received by the worldwide civilian flying population. We simulated flights globally from 2000 to 2013 using schedule data, applying a radiation propagation code to estimate the dose associated with each flight. Passengers flying in Europe and North America exceed the International Commission on Radiological Protection annual dose limits at an annual average of 510 or 420 flight hours per year, respectively. However, this falls to 160 or 120 h on specific routes under maximum exposure conditions.

Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing

PubMed Central

Edelman, Alison B; Cherala, Ganesh; Blue, Steven W; Erikson, David W; Jensen, Jeffrey T

2016-01-01

Objective To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations. Study design Healthy, reproductive-age women with obese and normal BMIs received 1.5 mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5 hours. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group. Results A total of 10 women enrolled and completed the study (normal BMI = 5, median 22.8 kg/m2, range 20.8–23.7; obese BMI = 5, 39.5 kg/m2, range 35.9–46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48 ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=0.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=0.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern. Conclusion Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women. Implications This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women. PMID:27000996

Dose-per-fraction escalation of accelerated hypofractionated three-dimensional conformal radiotherapy in locally advanced non-small cell lung cancer.

PubMed

Kepka, Lucyna; Tyc-Szczepaniak, Dobromira; Bujko, Krzysztof

2009-07-01

To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC). Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 through 2.8 Gy (level 1 escalation) to 2.9 Gy (level 2 escalation); the total dose increased, respectively, from 56.7 Gy through 58.8 Gy to 60.9 Gy. The dose to the elective area and the overall treatment time remained unchanged. Fit patients received two to three courses of chemotherapy before radiotherapy. The 2- and 3-year overall survival rates were 32 and 19%, respectively (median survival = 17 months). Of the patients, 7% had grade III acute esophageal toxicity and 6% had grade III or greater late pulmonary toxicity. Two of the nine patients who received the level 2 escalation (60.9 Gy) died of pulmonary toxicity. The study was terminated at a dose of 58.8 Gy and this schema was adopted as the institutional policy for treatment of stage III NSCLC. Although dose escalation with accelerated hypofractionated 3D-CRT was limited, the results and toxicity profiles obtained using this technique are promising.

Biological impact of low dose-rate simulated solar particle event radiation in vivo.

PubMed

Chang, P Y; Doppalapudi, R; Bakke, J; Wang, A; Menda, S; Davis, Z

2010-08-01

C57Bl6-lacZ animals were exposed to a range of low dose-rate simulated solar particle event (sSPE) radiation at the NASA-sponsored Research Laboratory (NSRL) at Brookhaven National Laboratory (BNL). Peripheral blood was harvested from animals from 1 to 12 days after total body irradiation (TBI) to quantify the level of circulating reticulocytes (RET) and micronucleated reticulocytes (MN-RET) as an early indicator of radiation-induced genotoxicity. Bone marrow lymphocytes and hippocampal tissues from each animal were collected at 12 days and up to two months, to evaluate dose-dependent late effects after sSPE exposure. Early hematopoietic changes show that the % RET was reduced up to 3 days in response to radiation exposure but recovered at 12 days postirradiation. The % MN-RET in peripheral blood was temporally regulated and dependant on the total accumulated dose. Total chromosome aberrations in lymphocytes increased linearly with dose within a week after radiation and remained significantly higher than the control values at 4 weeks after exposure. The level of aberrations in the irradiated animals returned to control levels by 8 weeks postirradiation. Measurements of chromosome 2 and 8 specific aberrations indicate that, consistent with conventional giemsa-staining methods, the level of aberrations is also not significantly higher than in control animals at 8 weeks postirradiation. The hippocampus was surveyed for differential transcriptional regulation of genes known to be associated with neurogenesis. Our results showed differential expression of neurotrophin and their associated receptor genes within 1 week after sSPE exposure. Progressive changes in the profile of expressed genes known to be involved in neurogenic signaling pathways were dependent on the sSPE dose. Our results to date suggest that radiation-induced changes in the hematopoietic system, i.e., chromosome aberrations in lymphocytes, are transient and do not persist past 4 weeks after radiation. On the other hand, alteration in the profile of genes known to be involved in neurotrophic functions in the hippocampal tissue appears to persist for up to 8 weeks after radiation exposure. Such temporal changes confirm that, although cytogenetic changes after a single dose of low-dose and low-dose-rate protons appear to be transient, the impact of this exposure is sufficient to lead to persistent dynamic changes in neuronal tissues long after the initial radiation exposure.

Synthesis, Characterization, Antioxidant Status, and Toxicity Study of Vanadium-Rutin Complex in Balb/c Mice.

PubMed

Roy, Souvik; Majumdar, Sumana; Singh, Amit Kumar; Ghosh, Balaram; Ghosh, Nilanjan; Manna, Subhadip; Chakraborty, Tania; Mallick, Sougato

2015-08-01

A new trend was developed for the formation of a complex between vanadium and flavonoid derivatives in order to increase the intestinal absorption and to reduce the toxicity of vanadium compounds. The vanadium-rutin complex was characterized by several spectroscopic techniques like ultraviolet (UV)-visible, Fourier transform infrared (FTIR), NMR, mass spectrometry, and microscopic evaluation by scanning electron microscopy. The mononuclear complex was formed by the interaction between vanadium and rutin with 1:2 metal to ligand stoichiometry. Antioxidant activity of the complex was evaluated by 1,1-diphenyl-2 picrylhydrazyl, ferric-reducing power, and 2,2'-azin-obis 3-ethylbenzothiazoline-6-sulphonic acid methods. It was shown that radical scavenging activity and ferric-reducing potential of free rutin was lower as compared with vanadium-rutin complex. The study was also investigated for oral acute toxicity and 28 days repeated oral subacute toxicity study of vanadium-rutin complex in balb/c mice. The vanadium-rutin complex showed mortality at a dose of 120 mg/kg in the balb/c mice. In 28 days repeated oral toxicity study, vanadium-rutin complex was administered to both sex of balb/c mice at dose levels of 90, 45, and 20 ppm, respectively. In addition, subacute toxicity study of vanadium-rutin complex (at 90 ppm dose level) showed increase levels of white blood cell (WBC), total bilirubin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen and decrease level of total protein (TP) as compared with control group. Histopathological study of vanadium-rutin showed structural alteration in the liver, kidney, and stomach at 90 ppm dose level. No observed toxic level of vanadium-rutin complex at 20 ppm dose level could be good for further study.

Radiation ecology issues associated with murine rodents and shrews in the Chernobyl exclusion zone.

PubMed

Gaschak, Sergey P; Maklyuk, Yulia A; Maksimenko, Andrey M; Bondarkov, Mikhail D; Jannik, G Timothy; Farfán, Eduardo B

2011-10-01

This article describes major studies performed by the Chernobyl Center's International Radioecology Laboratory (Slavutich, Ukraine) on radioecology of murine rodents and shrews inhabiting the Chernobyl Exclusion Zone. The article addresses the long-term (1986-2005) and seasonal dynamics of radioactive contamination of animals and reviews interspecies differences in radionuclide accumulations and factors affecting the radionuclide accumulations. It is shown that bioavailability of radionuclides in the "soil-to-plant" chain and a trophic specialization of animals play key roles in determining their actual contamination levels. The total absorbed dose rates in small mammals significantly reduced during the years following the Chernobyl Nuclear Power Plant accident. In 1986, the absorbed dose rate reached 1.3-6.0 Gy h(-1) in the central areas of the Chernobyl Exclusion Zone (the "Red Forest"). In 1988 and 1990, the total absorbed dose rates were 1.3 and 0.42 Gy h(-1), respectively. In 1995, 2000, and 2005, according to the present study, the total absorbed dose rates rarely exceeded 0.00023, 0.00018, and 0.00015 Gy h(-1), respectively. Contributions of individual radiation sources into the total absorbed dose are described.

Pediatric chest HRCT using the iDose4 Hybrid Iterative Reconstruction Algorithm: Which iDose level to choose?

NASA Astrophysics Data System (ADS)

Smarda, M.; Alexopoulou, E.; Mazioti, A.; Kordolaimi, S.; Ploussi, A.; Priftis, K.; Efstathopoulos, E.

2015-09-01

Purpose of the study is to determine the appropriate iterative reconstruction (IR) algorithm level that combines image quality and diagnostic confidence, for pediatric patients undergoing high-resolution computed tomography (HRCT). During the last 2 years, a total number of 20 children up to 10 years old with a clinical presentation of chronic bronchitis underwent HRCT in our department's 64-detector row CT scanner using the iDose IR algorithm, with almost similar image settings (80kVp, 40-50 mAs). CT images were reconstructed with all iDose levels (level 1 to 7) as well as with filtered-back projection (FBP) algorithm. Subjective image quality was evaluated by 2 experienced radiologists in terms of image noise, sharpness, contrast and diagnostic acceptability using a 5-point scale (1=excellent image, 5=non-acceptable image). Artifacts existance was also pointed out. All mean scores from both radiologists corresponded to satisfactory image quality (score ≤3), even with the FBP algorithm use. Almost excellent (score <2) overall image quality was achieved with iDose levels 5 to 7, but oversmoothing artifacts appearing with iDose levels 6 and 7 affected the diagnostic confidence. In conclusion, the use of iDose level 5 enables almost excellent image quality without considerable artifacts affecting the diagnosis. Further evaluation is needed in order to draw more precise conclusions.

The effects of slice thickness and radiation dose level variations on computer-aided diagnosis (CAD) nodule detection performance in pediatric chest CT scans

NASA Astrophysics Data System (ADS)

Emaminejad, Nastaran; Lo, Pechin; Ghahremani, Shahnaz; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael F.

2017-03-01

For pediatric oncology patients, CT scans are performed to assess treatment response and disease progression. CAD may be used to detect lung nodules which would reflect metastatic disease. The purpose of this study was to investigate the effects of reducing radiation dose and varying slice thickness on CAD performance in the detection of solid lung nodules in pediatric patients. The dataset consisted of CT scans of 58 pediatric chest cases, from which 7 cases had lung nodules detected by radiologist, and a total of 28 nodules were marked. For each case, the original raw data (sinogram data) was collected and a noise addition model was used to simulate reduced-dose scans of 50%, 25% and 10% of the original dose. In addition, the original and reduced-dose raw data were reconstructed at slice thicknesses of 1.5 and 3 mm using a medium sharp (B45) kernel; the result was eight datasets (4 dose levels x 2 thicknesses) for each case An in-house CAD tool was applied on all reconstructed scans, and results were compared with the radiologist's markings. Patient level mean sensitivities at 3mm thickness were 24%, 26%, 25%, 27%, and at 1.5 mm thickness were 23%, 29%, 35%, 36% for 10%, 25%, 50%, and 100% dose level, respectively. Mean FP numbers were 1.5, 0.9, 0.8, 0.7 at 3 mm and 11.4, 3.5, 2.8, 2.8 at 1.5 mm thickness for 10%, 25%, 50%, and 100% dose level respectively. CAD sensitivity did not change with dose level for 3mm thickness, but did change with dose for 1.5 mm. False Positives increased at low dose levels where noise values were high.

[Patients treated for differentiated thyroid cancer with negative 131I whole-body scans and elevated thyroglobulin levels: a possible course].

PubMed

Gutiérrez Cardo, A L; Rodríguez Rodríguez, J R; Borrego Dorado, I; Navarro González, E; Tirado Hospital, J L; Vázquez Albertino, R

2007-01-01

To verify the existence of patients with treated differentiated thyroid cancer (DTC) with negative 131I whole-body scanning (WBS) and high serum thyroglobulin (Tg) in the follow-up who evolve towards normalization without other therapy interventions. Retrospective revision of the periodic examinations established in the protocol for patients with DTC, analyzing the levels of Tg found with IRMA annually in those with hormonal treatment and every 1-5 years in absence of previous hormonal treatment to WBS. Minimum surveillance of 2 years. Those who had elevated levels of Tg and WBS and other negative imaging tests in their course were selected. The characteristics of the patients selected were analysed in those whose Tg levels evolved to normalization without specific medical or surgical treatment (Group I) and those who did not reach normalization of Tg (Group II). A total of 130 patients (17.93 %) with high levels of Tg and negative WBS were detected. Group I: 31 patients (4.28 %), 11 men and 20 women; average age at the moment of the diagnosis of 33.4 years (rank: 5-60); average surveillance: 12.4 years (+/- 7.4). 27 papillary and 4 follicular carcinoma. Average ablation dose: 3.260 GBq (88,1 mCi); average total I131 dose: 6.850 GBq (185.13 mCi). Tg normalization average time: 8.2 years. Group II: 99 patients (13.65 %), 27 men and 72 women. Average age of 40.4 years (rank: 7-76). Average surveillance: 9.8 years. 86 papillary and 13 follicular carcinoma. Average ablation dose: 3.266 GBq (88.28 mCi); average total 131I dose: 9.363 GBq (253,06 mCi). Two of the patients in group I had negative PET-FDG. There were 13 patients in whom progressive reduction of the levels of thyroglobulin without reaching normalization with negative PET-FDG was detected. In patients with radiated DTC, deferred normalization of the levels of the serum thyroglobulin is possible. Empirical treatments cannot be considered the only factor that contributes to this result, which can occur without the administration of high-doses of 131I.

Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells

PubMed Central

Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

2015-01-01

Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body γ-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to γ-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

Efficacy of two once-daily methylphenidate formulations compared across dose levels at different times of the day: preliminary indications from a secondary analysis of the COMACS study data.

PubMed

Sonuga-Barke, Edmund J S; Swanson, James M; Coghill, David; DeCory, Heleen H; Hatch, Simon J

2004-09-30

Methylphenidate (MPH) is commonly prescribed in the treatment of Attention-Deficit/Hyperactivity Disorder or ADHD. Concerta and Metadate CD are once-daily formulations of MPH using different delivery mechanisms resulting in different pharmacokinetic profiles. A recent study (COMACS) showed that for near-milligram (mg) equivalent daily doses, Metadate CD provides greater symptom control in the morning (1.5 through 4.5 hours post-dose), while Concerta provides greater control in the early evening (12 hours post-dose). Non-inferential comparison of effects for different dose levels of the two formulations suggested that equivalent levels of morning symptom control could be obtained with lower daily doses of Metadate CD than Concerta; the situation being reversed in the evening. The current paper presents a secondary analysis that provides a statistical test of these observations. The COMACS study was a multi-center, double-blind crossover study of Metadate CD, Concerta and placebo with each treatment administered for 1 week. Children were assigned on the basis of their pre-trial dosage to either high (Metadate CD 60 mg; Concerta 54 mg), medium (Metadate CD 40 mg; Concerta 36 mg) or low doses (Metadate CD 20 mg; Concerta 18 mg) of MPH, and attended a laboratory school on the 7th day for assessment at 7 sessions across the day. For the post-hoc comparisons across dose levels presented here, total SKAMP scores with the active treatments (adjusted for placebo response) were analyzed using an analysis of covariance, with a combined measure modeling placebo response across all time period as the covariate. Symptom control from 1.5 through 6.0 hours post-dose was as good with lower doses of Metadate CD (20 and 40 mg) as with higher doses of Concerta (36 and 54 mg, respectively). Lower daily doses of Concerta (18 and 36 mg) and higher doses of Metadate CD (40 and 60 mg, respectively) gave equivalent control at 7.5 and 12 hours with Metadate CD giving better control from1.5 through 6.0 hours post-dose. Different delivery profiles of Metadate CD and Concerta can be exploited to limit total daily exposure to MPH while at the same targeting a specific, especially clinically significant, period of the day. These results need to be confirmed in a study in which children are randomly allocated to different dose levels of the two formulations and plasma MPH concentrations are assessed simultaneously.

Time- and dose-dependent differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase enzymatic activity and mRNA level by vitamin E in rat blood cells.

PubMed

Hajiani, Maliheh; Razi, Farideh; Golestani, Aboualfazl; Frouzandeh, Mehdi; Owji, Ali Akbar; Khaghani, Shahnaz; Ghannadian, Naghmeh; Shariftabrizi, Ahmad; Pasalar, Parvin

2012-01-01

Vitamin E is the most important lipid-soluble antioxidant. Recently, it has been proposed as a gene regulator, and its gene modulation effects have been observed at different levels of gene expression and cell signaling. This study was performed to investigate the effects of vitamin E on the activity and expression of the most important endogenous antioxidant enzyme, superoxide dismutase (SOD), in rat plasma. Twenty-eight male Sprauge-Dawley rats were divided into four groups: control group and three dosing groups. The control group received the vehicle (liquid paraffin), and the dosing groups received twice-weekly intraperitoneal injections of 10, 30, and 100 mg/kg of vitamin E ((±)-α-Tocopherol) for 6 weeks. Quantitative real-time reverse transcription-polymerase chain reaction and enzyme assays were used to assess the levels of Cu/Zn-SOD and Mn-SOD mRNA and enzyme activity levels in blood cells at 0, 2, 4, and 6 weeks following vitamin E administration. Catalase enzyme activity and total antioxidant capacity were also assessed in plasma at the same time intervals. Mn-SOD activity was significantly increased in the 100 and 30 mg/kg dosing groups after 4 and 6 weeks, with corresponding significant increase in their mRNA levels. Cu/Zn-SOD activity was not significantly changed in response to vitamin E administration at any time points, whereas Cu/Zn-SOD mRNA levels were significantly increased after longer time points with high doses (30 and 100 mg/kg) of vitamin E. Catalase enzyme activity was transiently but significantly increased after 4 weeks of vitamin E treatment in 30 and 100 mg/kg dosing groups. Total antioxidant status was significantly increased after 4 and 6 weeks in the 100 mg/kg dosing group. Only the chronic administration of higher doses of alpha-tocopherol is associated with the increased activity and expression of Mn-SOD in rats. Cu/Zn-SOD activity and expression does not dramatically change in response to vitamin E.

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

PubMed Central

Liebman, Howard A.; Saleh, Mansoor N.; Bussel, James B.; Negrea, O. George; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2016-01-01

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066 PMID:27515248

Total integrated dose testing of solid-state scientific CD4011, CD4013, and CD4060 devices by irradiation with CO-60 gamma rays

NASA Technical Reports Server (NTRS)

Dantas, A. R. V.; Gauthier, M. K.; Coss, J. R.

1985-01-01

The total integrated dose response of three CMOS devices manufactured by Solid State Scientific has been measured using CO-60 gamma rays. Key parameter measurements were made and compared for each device type. The data show that the CD4011, CD4013, and CD4060 produced by this manufacturers should not be used in any environments where radiation levels might exceed 1,000 rad(Si).

Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

PubMed

Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

2014-09-01

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence of hypoglycemia was 4.1%, 2.0%, and 6.3%, respectively (P = 0.557). The currently proposed weight-based insulin glargine dose titration regimen is effective, tolerable, and user-friendly at achieving FBG target levels in hospitalized patients with hyperglycemia. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

PubMed

Sturgeon, Kathleen; Digiovanni, Laura; Good, Jerene; Salvatore, Domenick; Fenderson, Desiré; Domchek, Susan; Stopfer, Jill; Galantino, Mary Lou; Bryan, Cathy; Hwang, Wei-Ting; Schmitz, Kathryn

2016-08-01

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR. ©2016 American Association for Cancer Research.

Dose reduction potential of iterative reconstruction algorithms in neck CTA-a simulation study.

PubMed

Ellmann, Stephan; Kammerer, Ferdinand; Allmendinger, Thomas; Brand, Michael; Janka, Rolf; Hammon, Matthias; Lell, Michael M; Uder, Michael; Kramer, Manuel

2016-10-01

This study aimed to determine the degree of radiation dose reduction in neck CT angiography (CTA) achievable with Sinogram-affirmed iterative reconstruction (SAFIRE) algorithms. 10 consecutive patients scheduled for neck CTA were included in this study. CTA images of the external carotid arteries either were reconstructed with filtered back projection (FBP) at full radiation dose level or underwent simulated dose reduction by proprietary reconstruction software. The dose-reduced images were reconstructed using either SAFIRE 3 or SAFIRE 5 and compared with full-dose FBP images in terms of vessel definition. 5 observers performed a total of 3000 pairwise comparisons. SAFIRE allowed substantial radiation dose reductions in neck CTA while maintaining vessel definition. The possible levels of radiation dose reduction ranged from approximately 34 to approximately 90% and depended on the SAFIRE algorithm strength and the size of the vessel of interest. In general, larger vessels permitted higher degrees of radiation dose reduction, especially with higher SAFIRE strength levels. With small vessels, the superiority of SAFIRE 5 over SAFIRE 3 was lost. Neck CTA can be performed with substantially less radiation dose when SAFIRE is applied. The exact degree of radiation dose reduction should be adapted to the clinical question, in particular to the smallest vessel needing excellent definition.

Dosimetry for radiobiological studies of the human hematopoietic system

NASA Technical Reports Server (NTRS)

Beck, W. L.; Stokes, T. R.; Lushbaugh, C. C.

1972-01-01

A system for estimating individual bone marrow doses in therapeutic radiation exposures of leukemia patients was studied. These measurements are used to make dose response correlations and to study the effect of dose protraction on peripheral blood cell levels. Three irradiators designed to produce a uniform field of high energy gamma radiation for total body exposures of large animals and man are also used for radiobiological studies.

Analysis of the criteria used by the International Commission on Radiological Protection to justify the setting of numerical protection level values.

PubMed

2006-01-01

This report compiles the various numerical protection level values published by the International Commission on Radiological Protection (ICRP) since its 1990 Recommendations (Publication 60). Several terms are used to denominate the protection levels: individual dose limit, 'maximum' individual dose, dose constraint, exemption level, exclusion level, action level, or intervention level. The reasons provided by the Commission for selecting the associated numerical values is quoted as far as available. In some cases the rationale is not totally explicit in the original ICRP report concerned; in such cases the Task Group that prepared the present report have proposed their own interpretation. Originally, this report was prepared by a Task Group at CEPN, a French research and development center, in behalf of IRSN, a French public expert body engaged in radiological protection and nuclear safety. It is published here with kind permission by CEPN and IRSN.

ESTIMATION OF ADULT PATIENT DOSES FOR CHEST X-RAY EXAMINATIONS AND COMPARISON WITH DIAGNOSTIC REFERENCE LEVELS (DRLs).

PubMed

Bas Mor, H; Altinsoy, N; Söyler, I

2018-05-08

The aim of this study was to evaluate the radiation doses to patient during chest (posterior anterior/and lateral) examinations. The study was performed in three public hospitals of İstanbul province with a total of 300 adult patients. Entrance surface dose (ESD) measurements were conducted on computed radiography, digital radiography and screen film system. ESD was estimated by using International Atomic Energy Agency (IAEA) model and Davies model which are the common indirect models. Results were compared with diagnostic reference levels from the European Commission, IAEA and National Radiological Protection Board. Although the results are compatible with the international diagnostic reference levels, they present variations between the hospitals. Dose variations for the same type of X-ray examination support the idea that further optimization is possible.

Efficacy and safety of teneligliptin in addition to insulin therapy in type 2 diabetes mellitus patients on hemodialysis evaluated by continuous glucose monitoring.

PubMed

Yajima, Takahiro; Yajima, Kumiko; Hayashi, Makoto; Takahashi, Hiroshi; Yasuda, Keigo

2016-12-01

Appropriate glycemic control without hypoglycemia is important in patients with type 2 diabetes on hemodialysis. Teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, can be used without dose adjustment for these patients. Using continuous glucose monitoring (CGM), we evaluated the efficacy and safety of adding teneligliptin to insulin therapy. Twenty-one type 2 diabetes mellitus patients on hemodialysis treated with insulin were enrolled. After the adjustment of insulin dose, their blood glucose level was monitored by CGM. Insulin dose was reduced after teneligliptin administration. The median total daily insulin dose significantly reduced from 18 (9-24)U to 6 (0-14)U (p<0.0001). Maximum, mean, and standard deviation of blood glucose level on the hemodialysis and non-hemodialysis days did not change after teneligliptin administration. However, minimum blood glucose level was significantly elevated on the hemodialysis day after teneligliptin administration (from 3.9±1.0mmol/L to 4.4±0.9mmol/L, p=0.040). The incidence of asymptomatic hypoglycemia on the hemodialysis day detected by CGM significantly decreased from 38.1% to 19.0% (p=0.049). Teneligliptin may contribute toward reducing the total daily insulin dose and preventing hypoglycemic events on the hemodialysis day in type 2 diabetes mellitus patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mold and aflatoxin reduction by gamma radiation of packed hot peppers and their evolution during storage.

PubMed

Iqbal, Qumer; Amjad, Muhammad; Asi, Muhammad Rafique; Ariño, Agustin

2012-08-01

The effect of gamma radiation on moisture content, total mold counts, Aspergillus counts, and aflatoxins of three hot pepper hybrids (Sky Red, Maha, and Wonder King) was investigated. Whole dried peppers packed in polyethylene bags were gamma irradiated at 0 (control), 2, 4, and 6 kGy and stored at 25°C for 90 days. Gamma radiation proved to be effective in reducing total mold and Aspergillus counts in a dose-dependent relationship. Total mold counts in irradiated peppers immediately after treatments were significantly lowered compared with those in nonirradiated samples, achieving 90 and 99% reduction at 2- and 4-kGy doses, respectively. Aspergillus counts were significantly reduced, by 93 and 97%, immediately after irradiation at doses of 2 and 4 kGy, respectively. A radiation dose of 6 kGy completely eliminated the population of total molds and Aspergillus fungi. The evolution of total molds in control and irradiated samples indicated no further fungal proliferation during 3 months of storage at 25°C. Aflatoxin levels were slightly affected by radiation doses of 2 and 4 kGy and showed a nonsignificant reduction of 6% at the highest radiation dose of 6 kGy. The distinct effectiveness of gamma radiation in molds and aflatoxins can be explained by the target theory of food irradiation, which states that the likelihood of a microorganism or a molecule being inactivated by gamma rays increases as its size increases.

Three-Dimensional Dose Calculation for Total Body Irradiation

NASA Astrophysics Data System (ADS)

Ito, Akira

Bone Marrow Transplant (BMT) therapy has been a big success in the treatment of leukemia and other haematopoietic diseases 1 . Prior to BMT, total body irradiation (TBI) is given to the patient for the purpose of (1) killing leukemia cells in bone marrow, as well as in the whole body, and (2) producing immuno-suppressive status in the patient so that the donor's marrow cells will be transplanted without rejection. TBI employs a very large field photon beam to irradiate the whole body of the patient. A uniform dose distribution over the entire body is the treatment goal. To prevent the occurrence of a serious side effect (interstitial pneumonia), the lung dose should not exceed a certain level. This novel technique poses various new radiological physics problems. The accurate assessment of dose and dose distribution in the patient is essential. Physical and dosimetric problems associated with TBI are reviewed elsewhere 2,3 .

Functional Voice Testing Detects Early Changes in Vocal Pitch in Women During Testosterone Administration

PubMed Central

Pencina, Karol M.; Coady, Jeffry A.; Beleva, Yusnie M.; Bhasin, Shalender; Basaria, Shehzad

2015-01-01

Objective: To determine dose-dependent effects of T administration on voice changes in women with low T levels. Methods: Seventy-one women who have undergone a hysterectomy with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3, 6.25, 12.5, or 25 mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Voice handicap was measured by self-report using a validated voice handicap index questionnaire at baseline and 24 weeks after intervention. Functional voice testing was performed using the Kay Elemetrics-Computer Speech Lab to determine voice frequency, volume, and harmonics. Results: Forty-six women with evaluable voice data at baseline and after intervention were included in the analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 13, 83, 106, 122, and 250 ng/dL in the placebo, 3-, 6.25-, 12.5-, and 25-mg groups, respectively. Analyses of acoustic voice parameters revealed significant lowering of average pitch in the 12.5- and 25-mg dose groups compared to placebo (P < .05); these changes in pitch were significantly related to increases in T concentrations. No significant dose- or concentration-dependent changes in self-reported voice handicap index scores were observed. Conclusion: Testosterone administration in women with low T levels over 24 weeks was associated with dose- and concentration-dependent decreases in average pitch in the higher dose groups. These changes were seen despite the lack of self-reported changes in voice. PMID:25875779

Functional Voice Testing Detects Early Changes in Vocal Pitch in Women During Testosterone Administration.

PubMed

Huang, Grace; Pencina, Karol M; Coady, Jeffry A; Beleva, Yusnie M; Bhasin, Shalender; Basaria, Shehzad

2015-06-01

To determine dose-dependent effects of T administration on voice changes in women with low T levels. Seventy-one women who have undergone a hysterectomy with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3, 6.25, 12.5, or 25 mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Voice handicap was measured by self-report using a validated voice handicap index questionnaire at baseline and 24 weeks after intervention. Functional voice testing was performed using the Kay Elemetrics-Computer Speech Lab to determine voice frequency, volume, and harmonics. Forty-six women with evaluable voice data at baseline and after intervention were included in the analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 13, 83, 106, 122, and 250 ng/dL in the placebo, 3-, 6.25-, 12.5-, and 25-mg groups, respectively. Analyses of acoustic voice parameters revealed significant lowering of average pitch in the 12.5- and 25-mg dose groups compared to placebo (P < .05); these changes in pitch were significantly related to increases in T concentrations. No significant dose- or concentration-dependent changes in self-reported voice handicap index scores were observed. Testosterone administration in women with low T levels over 24 weeks was associated with dose- and concentration-dependent decreases in average pitch in the higher dose groups. These changes were seen despite the lack of self-reported changes in voice.

Bile acid changes after high-dose ursodeoxycholic acid treatment in primary sclerosing cholangitis: relation to disease progression

PubMed Central

Sinakos, Emmanouil; Marschall, Hanns-Ulrich; Kowdley, Kris V.; Befeler, Alex; Keach, Jill; Lindor, Keith

2010-01-01

High-dose (28-30mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), due to limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high dose UDCA versus placebo. Samples for analysis were obtained at baseline and at the end of treatment. The mean changes in UDCA (16.86 vs 0.05 μmol/L) and total bile acid (17.21 vs −0.55 μmol/L) levels were significantly higher in the UDCA group (n=29) compared to placebo (n=27) when pretreatment levels were compared (p<0.0001). LCA was also markedly increased (0.22 vs 0.01 μmol/L) in the UDCA group compared to placebo (p=0.001). No significant changes were detected for cholic acid (CA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). Patients (n=9) in the UDCA group who reached clinical endpoints of disease progression (development of cirrhosis, varices, liver transplantation or death) tend to have greater increase in their post-treatment total bile acid levels (34.99 vs 9.21 μmol/L) (p<0.08) compared to those who did not. Conclusion High-dose UDCA treatment in PSC patients results in marked UDCA enrichment and significant expansion of the total serum bile acid pool including lithocholic acid. PMID:20564380

RhBMP-2-induced radiculitis in patients undergoing transforaminal lumbar interbody fusion: relationship to dose.

PubMed

Villavicencio, Alan T; Burneikiene, Sigita

2016-10-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) remains the primary synthetic osteoinductive material used in spinal fusion surgery today. The early inflammation reaction to rhBMP-2 manifesting with radicular symptoms has been previously reported in patients undergoing transforaminal lumbar interbody fusion (TLIF). There is a disagreement with regard to the factors affecting its occurrence and whether such symptoms are dose dependent. The purpose of this analysis was to determine the incidence of rhBMP-2-induced radiculitis and its relationship to dose. A retrospective cohort analysis was performed of the prospectively collected data. All consecutive patients (n=204) who underwent one- or two-level TLIF and instrumented posterolateral fusion with an off-label rhBMP-2 use were included in this analysis. The patients who developed new radicular symptoms after initial improvement postoperatively and had sterile fluid collections indicative of inflammatory process, or in the absence of any structural abnormalities that would explain these symptoms on imaging studies, were deemed to have rhBMP-2-induced radiculitis. Magnetic resonance imaging (MRI) scans were obtained for all patients who developed postoperative radicular symptoms. Correlations between the total rhBMP-2 dose, dose per spinal level, and incidence of radiculitis were evaluated while controlling for age, sex, number of TLIF levels, and surgeon. The incidence of postoperative radiculitis was 11.3% (23 out of 204). The average total rhBMP-2 dose was 4.9 mg (range=2.1-12) and the average dose per spinal level was 3.8 mg (range=1.05-12). Logistic regression analysis did not identify any significant correlations between the rhBMP-2 doses and the incidence of radiculitis (p=.6). The incidence of rhBMP-2-induced radiculitis in patients undergoing TLIF is quite high, but there were no dose-related correlations found. The study, however, cannot rule out a possibility that a larger variation in bone morphogenetic protein (BMP) doses could still be a factor in the development of rhBMP-2-associated radiculitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats.

PubMed

Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor

2018-01-05

In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3,5,6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Copyright © 2017 Elsevier B.V. All rights reserved.

Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

PubMed Central

Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim

2014-01-01

Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

Dosimetric assessment from 212Pb inhalation at a thorium purification plant.

PubMed

Campos, M P; Pecequilo, B R S

2004-01-01

At the Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, Brazil, there is a facility (thorium purification plant) where materials with high thorium concentrations are manipulated. In order to estimate afterwards the lung cancer risk for the workers, the thoron daughter (212Pb) levels were assessed and the committed effective and lung committed equivalent doses for workers in place. A total of 28 air filter samples were measured by total alpha counting through the modified Kusnetz method, to determine the 212Pb concentraion. The committed effective dose and lung committed equivalent dose due to 212Pb inhalation were derived from compartmental analysis following the ICRP 66 lung compartmental model, and ICRP 67 lead metabolic model.

Prospective, open, multicentre Phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and cisplatin for esophageal carcinoma.

PubMed

Ma, Hong-Bing; Di, Zheng-Li; Wen, Jiao; Ke, Yue; Sun, Xiaodong; Ren, Juan

2015-02-01

Esophageal squamous cell carcinoma is increasingly treated with trimodality therapy. The objective of this Phase I/II clinical study is to assess the efficacy and safety of neoadjuvant radiochemotherapy with docetaxel and cisplatin and radiotherapy in patients with esophagectomy for locally advanced squamous cell carcinoma of the esophagus with neoadjuvant chemoradiotherapy. Patients with esophageal squamous cell carcinoma received radiochemotherapy (50 Gy/25 fractions during Weeks 1-5) using a three-dimensional conformal radiation therapy or intensity-modulated radiation therapy technique together with weekly docetaxel (20 mg/m(2) at dose levels 1 and 2, 25 mg/m(2) at dose level 3 on Weeks 1-5) and cisplatin (30 mg/m(2) at dose level 1, 40 mg/m(2) at dose levels 2 and 3 on Weeks 1-5) from January 2009 to December 2011. The dose-limiting toxicities and maximum tolerated dose were the primary endpoints and overall response rate and progression-free survival were the secondary endpoints. Over this timeframe, a total of 49 patients completed trimodality therapy. Thirteen patients were treated at dose level 1, 21 patients at dose level 2 and 15 patients at dose level 3.The maximum tolerated dose for docetaxel was 20 mg/m(2) and cisplatin 40 mg/m(2). The complete response or partial response was observed in 26.5% (13/49) of patients. Thirty-four patients (69.4%) were treated with neoadjuvant radiochemotherapy followed by surgical resection. The median progression-free survival and median overall survival for all patients (n = 49) were 8 and 17.2 months, respectively. The median overall survival was 27.5 months for patients treated at dose level 2. Neoadjuvant radiochemotherapy with docetaxel 20 mg/m(2) and cisplatin 40 mg/m(2) was effective and tolerable induction regimen in patients with esophageal tumors. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes.

PubMed

Lu, Ting; Sheng, Hongguang; Wu, Johnna; Cheng, Yuan; Zhu, Jianming; Chen, Yan

2012-06-01

For thousands of years, cinnamon has been used as a traditional treatment in China. However, there are no studies to date that investigate whether cinnamon supplements are able to aid in the treatment of type 2 diabetes in Chinese subjects. We hypothesized cinnamon should be effective in improving blood glucose control in Chinese patients with type 2 diabetes. To address this hypothesis, we performed a randomized, double-blinded clinical study to analyze the effect of cinnamon extract on glycosylated hemoglobin A(1c) and fasting blood glucose levels in Chinese patients with type 2 diabetes. A total of 66 patients with type 2 diabetes were recruited and randomly divided into 3 groups: placebo and low-dose and high-dose supplementation with cinnamon extract at 120 and 360 mg/d, respectively. Patients in all 3 groups took gliclazide during the entire 3 months of the study. Both hemoglobin A(1c) and fasting blood glucose levels were significantly reduced in patients in the low- and high-dose groups, whereas they were not changed in the placebo group. The blood triglyceride levels were also significantly reduced in the low-dose group. The blood levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and liver transaminase remained unchanged in the 3 groups. In conclusion, our study indicates that cinnamon supplementation is able to significantly improve blood glucose control in Chinese patients with type 2 diabetes. Copyright © 2012 Elsevier Inc. All rights reserved.

Benchmarking pediatric cranial CT protocols using a dose tracking software system: a multicenter study.

PubMed

De Bondt, Timo; Mulkens, Tom; Zanca, Federica; Pyfferoen, Lotte; Casselman, Jan W; Parizel, Paul M

2017-02-01

To benchmark regional standard practice for paediatric cranial CT-procedures in terms of radiation dose and acquisition parameters. Paediatric cranial CT-data were retrospectively collected during a 1-year period, in 3 different hospitals of the same country. A dose tracking system was used to automatically gather information. Dose (CTDI and DLP), scan length, amount of retakes and demographic data were stratified by age and clinical indication; appropriate use of child-specific protocols was assessed. In total, 296 paediatric cranial CT-procedures were collected. Although the median dose of each hospital was below national and international diagnostic reference level (DRL) for all age categories, statistically significant (p-value < 0.001) dose differences among hospitals were observed. The hospital with lowest dose levels showed smallest dose variability and used age-stratified protocols for standardizing paediatric head exams. Erroneous selection of adult protocols for children still occurred, mostly in the oldest age-group. Even though all hospitals complied with national and international DRLs, dose tracking and benchmarking showed that further dose optimization and standardization is possible by using age-stratified protocols for paediatric cranial CT. Moreover, having a dose tracking system revealed that adult protocols are still applied for paediatric CT, a practice that must be avoided. • Significant differences were observed in the delivered dose between age-groups and hospitals. • Using age-adapted scanning protocols gives a nearly linear dose increase. • Sharing dose-data can be a trigger for hospitals to reduce dose levels.

Diagnostic radiation exposure in pediatric trauma patients.

PubMed

Brunetti, Marissa A; Mahesh, Mahadevappa; Nabaweesi, Rosemary; Locke, Paul; Ziegfeld, Susan; Brown, Robert

2011-02-01

The amount of imaging studies performed for disease diagnosis has been rapidly increasing. We examined the amount of radiation exposure that pediatric trauma patients receive because they are an at-risk population. Our hypothesis was that pediatric trauma patients are exposed to high levels of radiation during a single hospital visit. Retrospective review of children who presented to Johns Hopkins Pediatric Trauma Center from July 1, 2004, to June 30, 2005. Radiographic studies were recorded for each patient and doses were calculated to give a total effective dose of radiation. All radiographic studies that each child received during evaluation, including any associated hospital admission, were included. A total of 945 children were evaluated during the study year. A total of 719 children were included in the analysis. Mean age was 7.8 (±4.6) years. Four thousand six hundred three radiographic studies were performed; 1,457 were computed tomography (CT) studies (31.7%). Average radiation dose was 12.8 (±12) mSv. We found that while CT accounted for only 31.7% of the radiologic studies performed, it accounted for 91% of the total radiation dose. Mean dose for admitted children was 17.9 (±13.8) mSv. Mean dose for discharged children was 8.4 (±7.8) mSv (p<0.0001). Burn injuries had the lowest radiation dose [1.2 (±2.6) mSv], whereas motor vehicle collision victims had the highest dose [18.8 (±14.7) mSv]. When the use of radiologic imaging is considered essential, cumulative radiation exposure can be high. In young children with relatively long life spans, the benefit of each imaging study and the cumulative radiation dose should be weighed against the long-term risks of increased exposure.

Use of a hybrid iterative reconstruction technique to reduce image noise and improve image quality in obese patients undergoing computed tomographic pulmonary angiography.

PubMed

Kligerman, Seth; Mehta, Dhruv; Farnadesh, Mahmmoudreza; Jeudy, Jean; Olsen, Kathryn; White, Charles

2013-01-01

To determine whether an iterative reconstruction (IR) technique (iDose, Philips Healthcare) can reduce image noise and improve image quality in obese patients undergoing computed tomographic pulmonary angiography (CTPA). The study was Health Insurance Portability and Accountability Act compliant and approved by our institutional review board. A total of 33 obese patients (average body mass index: 42.7) underwent CTPA studies following standard departmental protocols. The data were reconstructed with filtered back projection (FBP) and 3 iDose strengths (iDoseL1, iDoseL3, and iDoseL5) for a total of 132 studies. FBP data were collected from 33 controls (average body mass index: 22) undergoing CTPA. Regions of interest were drawn at 6 identical levels in the pulmonary artery (PA), from the main PA to a subsegmental branch, in both the control group and study groups using each algorithm. Noise and attenuation were measured at all PA levels. Three thoracic radiologists graded each study on a scale of 1 (very poor) to 5 (ideal) by 4 categories: image quality, noise, PA enhancement, and "plastic" appearance. Statistical analysis was performed using an unpaired t test, 1-way analysis of variance, and linear weighted κ. Compared with the control group, there was significantly higher noise with FBP, iDoseL1, and iDoseL3 algorithms (P<0.001) in the study group. There was no significant difference between the noise in the control group and iDoseL5 algorithm in the study group. Analysis within the study group showed a significant and progressive decrease in noise and increase in the contrast-to-noise ratio as the level of IR was increased (P<0.001). Compared with FBP, readers graded overall image quality as being higher using iDoseL1 (P=0.0018), iDoseL3 (P<0.001), and iDoseL5 (P<0.001). Compared with FBP, there was subjective improvement in image noise and PA enhancement with increasing levels of iDose. The use of an IR technique leads to qualitative and quantitative improvements in image noise and image quality in obese patients undergoing CTPA.

A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

PubMed

Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

2005-08-01

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Bowers, Karen J; McAllister, Kelly B; Ray, Meredith; Heitz, Corey

2017-06-01

This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids; 2) to measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids; 3) to compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids; 4) to monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids; and 5) to identify effect variation between different subgroups of patients, with the purpose of focusing future research. We hypothesized that low-dose ketamine, compared to placebo, as an adjunctive treatment to opioids would result in better pain control over 2 hours and greater patient satisfaction with pain control; further, this protocol will result in a lower opioid dosage over 2 hours. This was a randomized, double-blinded, placebo-controlled trial at a single academic emergency department evaluating the use of ketamine versus placebo in conjunction with opioids for moderate to severe pain. Subjects with a continued high level of pain after an initial dose of opioid analgesia were randomized to receive either 0.1 mg/kg ketamine or placebo prior to protocol-based dosing of additional opioid analgesia, if required. Over 120 minutes, subjects were assessed for pain level (0-10), satisfaction with pain control (0-4), side effects, sedation level, and need for additional pain medication. Total opioid dose, including the initial dose, was compared between groups. Sixty-three subjects were randomized to the placebo group and 53 to the ketamine group. No significant differences were found in demographics between the groups. Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo (p = 0.015). Total opioid dose was lower in the ketamine group (mean ± SD = 9.95 ± 4.83 mg) compared to placebo (mean ± SD = 12.81 ± 6.81 mg; p = 0.02). Satisfaction did not differ between groups. Fewer patients in the ketamine group required additional opioid doses. More patients reported light-headedness and dizziness in the ketamine group. Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia. More side effects were reported in the ketamine group (51% vs. 19%), but the side effect profile appears tolerable. © 2017 by the Society for Academic Emergency Medicine.

Acute, 28days sub acute and genotoxic profiling of Quercetin-Magnesium complex in Swiss albino mice.

PubMed

Ghosh, Nilanjan; Sandur, Rajendra; Ghosh, Deepanwita; Roy, Souvik; Janadri, Suresh

2017-02-01

Quercetin-Magnesium complex is one of the youngest alkaline rare earth metal (Magnesium) complexes with flavonoids (Quercetin) in organo-metalic family. Earlier studies describe the details of the complex formation, characterization and antioxidant study of the complex but toxicity profile is still under darkness. The present study was taken up to investigate the oral acute toxicity, 28days repeated oral sub-acute toxicity study and genotoxicity study of Quercetin-Magnesium complex in Swiss albino mice. Quercetin-Magnesium complex showed mortality at a dose of 185mg/kg in the Swiss albino mice. In 28days repeated oral toxicity study, Quercetin-Magnesium complex was administered to both sex of Swiss albino mice at dose levels of 150, 130 and 100mg/kg body weight respectively. Where 150mg/kg dose shows increased levels of white blood cells and changes in total protein, serum creatinine and blood urea nitrogen. Histopathological study of Quercetin-Magnesium complex shows minor structural alteration in kidney at 150mg/kg dose. No observed toxic level found in 130mg/kg or below doses. No genotoxic effect found in any doses of the complex. Therefore 130mg/kg or below dose level could be better for further study. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

PubMed

Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

1992-02-01

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

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

Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong

Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{supmore » 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.« less

Effects of irradiation source and dose level on quality characteristics of processed meat products

NASA Astrophysics Data System (ADS)

Ham, Youn-Kyung; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Kim, Yong-Jae; Choi, Yun-Sang; Song, Beom-Seok; Park, Jong-Heum; Kim, Cheon-Jei

2017-01-01

The effect of irradiation source (gamma-ray, electron-beam, and X-ray) and dose levels on the physicochemical, organoleptic and microbial properties of cooked beef patties and pork sausages was studied, during 10 days of storage at 30±1 °C. The processed meat products were irradiated at 0, 2.5, 5, 7.5, and 10 kGy by three different irradiation sources. The pH of cooked beef patties and pork sausages was unaffected by irradiation sources or their doses. The redness of beef patties linearly decreased with increasing dose level (P<0.05), obviously by e-beam irradiation compared to gamma-ray and X-ray (P<0.05). The redness of pork sausages was increased by gamma-ray irradiation, whereas it decreased by e-beam irradiation depending on absorbed dose level. No significant changes in overall acceptability were observed for pork sausages regardless of irradiation source (P>0.05), while gamma-ray irradiated beef patties showed significantly decreased overall acceptability in a dose-dependent manner (P<0.05). Lipid oxidation of samples was accelerated by irradiation depending on irradiation sources and dose levels during storage at 30 °C. E-beam reduced total aerobic bacteria of beef patties more effectively, while gamma-ray considerably decreased microbes in pork sausages as irradiation dose increased. The results of this study indicate that quality attributes of meat products, in particular color, lipid oxidation, and microbial properties are significantly influenced by the irradiation sources.

Effect of radiation dose reduction and iterative reconstruction on computer-aided detection of pulmonary nodules: Intra-individual comparison.

PubMed

Den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evert-Jan P A; Milles, Julien; Schilham, Arnold M R; Lammers, Jan-Willem; de Jong, Pim A; Leiner, Tim; Budde, Ricardo P J

2016-02-01

To evaluate the effect of radiation dose reduction and iterative reconstruction (IR) on the performance of computer-aided detection (CAD) for pulmonary nodules. In this prospective study twenty-five patients were included who were scanned for pulmonary nodule follow-up. Image acquisition was performed at routine dose and three reduced dose levels in a single session by decreasing mAs-values with 45%, 60% and 75%. Tube voltage was fixed at 120 kVp for patients ≥ 80 kg and 100 kVp for patients < 80 kg. Data were reconstructed with filtered back projection (FBP), iDose(4) (levels 1,4,6) and IMR (levels 1-3). All noncalcified solid pulmonary nodules ≥ 4 mm identified by two radiologists in consensus served as the reference standard. Subsequently, nodule volume was measured with CAD software and compared to the reference consensus. The numbers of true-positives, false-positives and missed pulmonary nodules were evaluated as well as the sensitivity. Median effective radiation dose was 2.2 mSv at routine dose and 1.2, 0.9 and 0.6 mSv at respectively 45%, 60% and 75% reduced dose. A total of 28 pulmonary nodules were included. With FBP at routine dose, 89% (25/28) of the nodules were correctly identified by CAD. This was similar at reduced dose levels with FBP, iDose(4) and IMR. CAD resulted in a median number of false-positives findings of 11 per scan with FBP at routine dose (93% of the CAD marks) increasing to 15 per scan with iDose(4) (95% of the CAD marks) and 26 per scan (96% of the CAD marks) with IMR at the lowest dose level. CAD can identify pulmonary nodules at submillisievert dose levels with FBP, hybrid and model-based IR. However, the number of false-positive findings increased using hybrid and especially model-based IR at submillisievert dose while dose reduction did not affect the number of false-positives with FBP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

PubMed

Kojima, Shuji

2006-10-01

We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

Terrestrial Gamma Radiation Dose Rate of West Sarawak

NASA Astrophysics Data System (ADS)

Izham, A.; Ramli, A. T.; Saridan Wan Hassan, W. M.; Idris, H. N.; Basri, N. A.

2017-10-01

A study of terrestrial gamma radiation (TGR) dose rate was conducted in west of Sarawak, covering Kuching, Samarahan, Serian, Sri Aman, and Betong divisions to construct a baseline TGR dose rate level data of the areas. The total area covered was 20,259.2 km2, where in-situ measurements of TGR dose rate were taken using NaI(Tl) scintillation detector Ludlum 19 micro R meter NaI(Tl) approximately 1 meter above ground level. Twenty-nine soil samples were taken across the 5 divisions covering 26 pairings of 9 geological formations and 7 soil types. A hyperpure Germanium detector was then used to find the samples' 238U, 232Th, and 40K radionuclides concentrations producing a correction factor Cf = 0.544. A total of239 measured data were corrected with Cf resulting in a mean Dm of 47 ± 1 nGy h-1, with a range between 5 nGy h-1 - 103 nGy h-1. A multiple regression analysis was conducted between geological means and soil types means against the corrected TGR dose rate Dm, generating Dg,s= 0.847Dg+ 0.637Ds- 22.313 prediction model with a normalized Beta equation of Dg,s= 0.605Dg+ 0.395Ds. The model has an 84.6% acceptance of Whitney- Mann test null hypothesis when tested against the corrected TGR dose rates.

Protective effects of l-glutamine against toxicity of deltamethrin in the cerebral tissue

PubMed Central

Varol, Sefer; Özdemir, Hasan Hüseyin; Çevik, Mehmet Uğur; Altun, Yaşar; Ibiloğlu, Ibrahim; Ekinci, Aysun; Ibiloğlu, Aslıhan Okan; Balduz, Metin; Arslan, Demet; Tekin, Recep; Aktar, Fesih; Aluçlu, Mehmet Ufuk

2016-01-01

Background Deltamethrin (DLM) is a broad-spectrum synthetic dibromo-pyrethroid pesticide that is widely used for agricultural and veterinary purposes. However, human exposure to the pesticide leads to neurotoxicity. Glutamine is one of the principal, free intracellular amino acids and may also be an antioxidant. This study was undertaken in order to examine the neuroprotective and antioxidant potential of l-glutamine against DLM toxicity in female Wistar albino rats. Materials and methods The rats were divided into the following groups (n=10): Group I: control (distilled water; 10 mL/kg, po one dose), Group II: l-glutamine (1.5 g/kg, po one dose), Group III: DLM (35 mg/kg, po one dose), and Group IV: DLM (35 mg/kg, po one dose) and l-glutamine (1.5 g/kg, po one dose after 4 hours). Total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels and apoptosis were evaluated in brain tissue. Results DLM-treated animals had a significant increase in brain biochemical parameters, as well as TOS and TAS. Furthermore, the histopathological examination showed neuronal cell degeneration in the cerebral tissue. l-Glutamine treatment decreased the elevated brain levels of TOS and neuronal cell degeneration. There was no difference in tumor necrosis factor-α, IL-1β, and IL-6 levels between the groups. Conclusion l-Glutamine may reduce the toxic effects of DLM in the cerebral tissue through antioxidant properties. PMID:27143900

Pharmacokinetic and Genomic Effects of Arsenite in Drinking Water on Mouse Lung in a 30-Day Exposure

PubMed Central

Chilakapati, Jaya; Wallace, Kathleen; Hernandez-Zavala, Araceli; Moore, Tanya; Ren, Hongzu

2015-01-01

The 2 objectives of this subchronic study were to determine the arsenite drinking water exposure dependent increases in female C3H mouse liver and lung tissue arsenicals and to characterize the dose response (to 0, 0.05, 0.25, 1, 10, and 85 ppm arsenite in drinking water for 30 days and a purified AIN-93M diet) for genomic mouse lung expression patterns. Mouse lungs were analyzed for inorganic arsenic, monomethylated, and dimethylated arsenicals by hydride generation atomic absorption spectroscopy. The total lung mean arsenical levels were 1.4, 22.5, 30.1, 50.9, 105.3, and 316.4 ng/g lung tissue after 0, 0.05, 0.25, 1, 10, and 85 ppm, respectively. At 85 ppm, the total mean lung arsenical levels increased 14-fold and 131-fold when compared to either the lowest noncontrol dose (0.05 ppm) or the control dose, respectively. We found that arsenic exposure elicited minimal numbers of differentially expressed genes (DEGs; 77, 38, 90, 87, and 87 DEGs) after 0.05, 0.25, 1, 10, and 85 ppm, respectively, which were associated with cardiovascular disease, development, differentiation, apoptosis, proliferation, and stress response. After 30 days of arsenite exposure, this study showed monotonic increases in mouse lung arsenical (total arsenic and dimethylarsinic acid) concentrations but no clear dose-related increases in DEG numbers. PMID:26674514

Pharmacokinetic and Genomic Effects of Arsenite in Drinking Water on Mouse Lung in a 30-Day Exposure.

PubMed

Chilakapati, Jaya; Wallace, Kathleen; Hernandez-Zavala, Araceli; Moore, Tanya; Ren, Hongzu; Kitchin, Kirk T

2015-01-01

The 2 objectives of this subchronic study were to determine the arsenite drinking water exposure dependent increases in female C3H mouse liver and lung tissue arsenicals and to characterize the dose response (to 0, 0.05, 0.25, 1, 10, and 85 ppm arsenite in drinking water for 30 days and a purified AIN-93M diet) for genomic mouse lung expression patterns. Mouse lungs were analyzed for inorganic arsenic, monomethylated, and dimethylated arsenicals by hydride generation atomic absorption spectroscopy. The total lung mean arsenical levels were 1.4, 22.5, 30.1, 50.9, 105.3, and 316.4 ng/g lung tissue after 0, 0.05, 0.25, 1, 10, and 85 ppm, respectively. At 85 ppm, the total mean lung arsenical levels increased 14-fold and 131-fold when compared to either the lowest noncontrol dose (0.05 ppm) or the control dose, respectively. We found that arsenic exposure elicited minimal numbers of differentially expressed genes (DEGs; 77, 38, 90, 87, and 87 DEGs) after 0.05, 0.25, 1, 10, and 85 ppm, respectively, which were associated with cardiovascular disease, development, differentiation, apoptosis, proliferation, and stress response. After 30 days of arsenite exposure, this study showed monotonic increases in mouse lung arsenical (total arsenic and dimethylarsinic acid) concentrations but no clear dose-related increases in DEG numbers.

Metabolic changes in humans following total body irradiation. Report for February 1960-October 1961

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

Not Available

These studies are designed to obtain new information about the metabolic effects of total body and partial body irradiation so as to have a better understanding of the acute and subacute effects of irradiation in the human. The initial studies are pointed toward the elucidation of biological indicators of radiation effects in humans. The major parameters being investigated at present are urinary amino aciduria and alterations in immunological patterns. Certain other parameters such as creatine and creatinine excretion and hematological effects are also being followed. The long-term program envisions carrying out the various observations at dose levels of 100 radmore » and gradually increasing the dose to 150, 200, 250 and 300 rad. Eventually doses up to 600 rad are anticipated. Also comparison of effects of radiomimetic drugs with total body radiation will be studied.« less

The total ozone and UV solar radiation over Stara Zagora, Bulgaria

NASA Astrophysics Data System (ADS)

Mendeva, B. D.; Gogosheva, Ts. N.; Petkov, B. H.; Krastev, D. G.

The results from direct ground-based solar UV irradiance measurements and the total ozone content (TOC) over Stara Zagora (42° 25'N, 25° 37'E), Bulgaria are presented. During the period 1999-2003 the TOC data show seasonal variations, typical for the middle latitudes - maximum in the spring and minimum in the autumn. The comparison between TOC ground-based data and Global Ozone Monitoring Experiment (GOME) satellite-borne ones shows a seasonal dependence of the differences between them. A strong negative relationship between the total ozone and the 305 nm wavelength irradiance was found. The dependence between the two variables is significant ( r = -0.62 ± 0.18) at 98% confidence level. The direct sun UV doses for some specific biological effects (erythema and eyes) are obtained. The estimation of the radiation amplification factor RAF shows that the ozone reduction by 1% increases the erythemal dose by 2.3%. The eye-damaging doses are more influenced by the TOC changes and in this case RAF = -2.7%. The amount of these biological doses depended on the solar altitude over the horizon. This dependence was not so strong when the total ozone content in the atmosphere was lower.

[The effect of bemetil on the production of DNA antibodies in patients with systemic lupus erythematosus].

PubMed

Lisitsyna, T A; Durnev, A D; Ivanova, M M; Speranskiĭ, A I; Seredenin, S B; Nasonova, V A

1999-01-01

The levels of autoantibodies against DNA in blood serum and severity of the disease were evaluated prior to, during, and after 8-week treatment of patients suffering from lupus erythematosus systemicus (LES) with prednisolonum (daily dose of 5-60 mg/kg, 15 patient) and with prednisolonum in combination with cyclophosphane (CP) (a total dose of 2-4 mg/kg per os. 15 patients), or bemithyl doses of 500-750 mg/day per os (15 patients) or bemithyl in combination with CP (the same doses, 16 patients). It was shown that introduction of bemithyl into LES treatment schedule significantly lowered the level of autoantibodies against DNA evaluated in immunoassay and reduced LES severity assessed using standard SLEDAI-1 and ECLAM scales.

Implementation and application of an interactive user-friendly validation software for RADIANCE

NASA Astrophysics Data System (ADS)

Sundaram, Anand; Boonn, William W.; Kim, Woojin; Cook, Tessa S.

2012-02-01

RADIANCE extracts CT dose parameters from dose sheets using optical character recognition and stores the data in a relational database. To facilitate validation of RADIANCE's performance, a simple user interface was initially implemented and about 300 records were evaluated. Here, we extend this interface to achieve a wider variety of functions and perform a larger-scale validation. The validator uses some data from the RADIANCE database to prepopulate quality-testing fields, such as correspondence between calculated and reported total dose-length product. The interface also displays relevant parameters from the DICOM headers. A total of 5,098 dose sheets were used to test the performance accuracy of RADIANCE in dose data extraction. Several search criteria were implemented. All records were searchable by accession number, study date, or dose parameters beyond chosen thresholds. Validated records were searchable according to additional criteria from validation inputs. An error rate of 0.303% was demonstrated in the validation. Dose monitoring is increasingly important and RADIANCE provides an open-source solution with a high level of accuracy. The RADIANCE validator has been updated to enable users to test the integrity of their installation and verify that their dose monitoring is accurate and effective.

The value of fixed rasburicase dosing versus weight-based dosing in the treatment and prevention of tumor lysis syndrome.

PubMed

Boutin, Alyssa; Blackman, Alison; O'Sullivan, David M; Forcello, Nicholas

2018-01-01

Background Rasburicase is a recombinant urate oxidase enzyme used for the treatment and prevention of tumor lysis syndrome. Our objective was to assess the efficacy of indication-based, low-dose rasburicase administration compared to the Food and Drug Administration-approved weight-based dosing. Methods This was a retrospective cohort study utilizing data from a tertiary medical center including patients admitted from 2012 to 2016, who received at least one dose of rasburicase. The primary outcome was achieving a uric acid level less than 7.5 mg/dl after a single dose of rasburicase in the preprotocol (Food and Drug Administration-approved weight-based dosing) and postprotocol (indication-based, low-dose) groups. Secondary outcomes included the change in uric acid levels between the pre- and postprotocol groups, adherence to the new institutional protocol, need for repeat rasburicase doses, and a cost analysis. Results Sixty-four patients received at least one dose of rasburicase between 1 January 2012 and 1 December 2016. Twenty-seven (79.4%) doses in the preprotocol group and 28 (82.4%) doses in the postprotocol group successfully achieved a uric acid level less than 7.5 mg/dl after a single dose of rasburicase (p=1.000). The average total monthly cost of rasburicase was reduced by 59.9% after adoption of the new protocol. Conclusions Indication-based, low-dose rasburicase displayed significantly more value when compared to weight-based dosing as shown by achieving cost savings without compromising clinical efficacy.

Dose rate effects on array CCDs exposed by Co-60 γ rays induce saturation output degradation and annealing tests

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Chen, Wei; He, Baoping

The experimental tests of dose rate and annealing effects on array charge-coupled devices (CCDs) are presented. The saturation output voltage (V{sub S}) versus the total dose at the dose rates of 0.01, 0.1, 1.0, 10.0 and 50 rad(Si)/s are compared. Annealing tests are performed to eliminate the time-dependent effects. The V{sub S} degradation levels depend on the dose rates. The V{sub S} degradation mechanism induced by dose rate and annealing effects is analyzed. The V{sub S} at 20 krad(Si) with the dose rate of 0.03 rad(Si)/s are supplemented to assure the degradation curves between the dose rates of 0.1 andmore » 0.01 rad(Si)/s. The CCDs are divided into two groups, with one group biased and the other unbiased during {sup 60}Co γ radiation. The V{sub S} degradation levels of the biased CCDs during radiation are more severe than that of the unbiased CCDs.« less

Total skin electron irradiation for mycosis fungoides: relationship between acute toxicities and measured dose at different anatomic sites.

PubMed

Desai, K R; Pezner, R D; Lipsett, J A; Vora, N L; Luk, K H; Wong, J Y; Chan, S L; Findley, D O; Hill, L R; Marin, L A

1988-09-01

From June 1978 to June 1986, 50 patients with primary and recurrent mycosis fungoides were treated with total skin electron irradiation (TSEI), using the Stanford technique, to a total dose of 3600 cGy. TSEI was used alone, or in combination with low dose total body photon irradiation, or MOPP. Thermoluminescent dosimeter (TLD) measurements of the prescribed skin dose were obtained on twenty patients. The dorsum of the foot was 24% higher. The axillae, the bottom, and the arch of the foot were significantly underdosed. Frequencies of acute toxicities noted at 2000 cGy were: Skin, Grade I-II (RTOG) 80%. Partial epilation: scalp, 100%; eyebrows and at eyelashes, 20%. Nail dystrophy, 48%. Edema: hands and feet, 44%. Bullae: dorsum of feet, 8%; hands, 4%; and 3600 cGy: Skin, grade III 22%. Total epilation: scalp, 66%; eyebrows and eyelashes, 56%. Nail loss, 38%. Edema: hands and feet, 76%. Bullae: dorsum of feet, 34%; hands, 12%. Conjunctivitis, 4%. Large bullae, were more significant on the dorsum of the feet. Severe moist desquamation occurred in eight patients who had ulcerated lesions on initial presentation. Three patients were hospitalized due to ulceration and skin infection. All patients completed treatment after a short to moderate break. No patient developed skin necrosis, or corneal ulceration. No correlation exists between dose level, degree and onset of toxicity with previous chemotherapy or TBI. We conclude that the overall toxicity of TSEI is well tolerated.

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs

PubMed Central

Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-01-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day. PMID:25874036

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs.

PubMed

Nam, Chunja; Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-03-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

High level gamma radiation effects on Cernox™ cryogenic temperature sensors

NASA Astrophysics Data System (ADS)

Courts, S. S.

2017-12-01

Cryogenic temperature sensors are used in high energy particle colliders to monitor the temperatures of superconducting magnets, superconducting RF cavities, and cryogen infrastructure. While not intentional, these components are irradiated by leakage radiation during operation of the collider. A common type of cryogenic thermometer used in these applications is the Cernox™ resistance thermometer (CxRT) manufactured by Lake Shore Cryotronics, Inc. This work examines the radiation-induced calibration offsets on CxRT models CX-1050-SD-HT and CX-1080-SD-HT resulting from exposure to very high levels of gamma radiation. Samples from two different wafers of each of the two models tested were subjected to a gamma radiation dose ranging from 10 kGy to 5 MGy. Data were analysed in terms of the temperature-equivalent resistance change between pre- and post-irradiation calibrations. The data show that the resistance of these devices decreased following irradiation resulting in positive temperature offsets across the 1.4 K to 330 K temperature range. Variations in response were observed between wafers of the same CxRT model. Overall, the offsets increased with increasing temperature and increasing gamma radiation dose. At 1.8 K, the average offset increased from 0 mK to +13 mK as total dose increased from 10 kGy to 5 MGy. At 4.2 K, the average offset increased from +4 mK to +33 mK as total dose increased from 10 kGy to 5 MGy. Equivalent temperature offset data are presented over the 1.4 K to 330 K temperature range by CxRT model, wafer, and total gamma dose.

Phase I Study of Oral S-1 Plus Cisplatin With Concurrent Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer

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

Kaira, Kyoichi; Sunaga, Noriaki; Yanagitani, Noriko

Purpose: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: S-1 was administered orally twice daily for 14 days and cisplatin on Days 1 and 8 of each cycle; this was repeated every 3 weeks. Doses of each drug were planned as follows: level 0, 50/40; level 1, 60/40; level 2, 70/40; level 3, 80/40 (S-1 [mg/m{sup -2}/day{sup -1}]/cisplatin [mg/m{sup -2}/day{sup -1}]). Thoracic radiation therapy was administered in 2 Gy fractions five times weekly to amore » total dose of 60 Gy. Results: Ten patients were enrolled in this study. All patients received 60 Gy of thoracic radiotherapy and 7 (70%) patients received four cycles of chemotherapy. At level 1, 2 of 3 patients experienced a delay exceeding 10 days in the cisplatin administration of Day 29. Grade 4 neutropenia and Grade 3 fever occurred in 1 and 1 patients, respectively. Nonhematologic toxicities were mild. None developed {>=}Grade 3 esophagitis or lung toxicity. At level 0, 2 of 7 patients developed dose-limiting toxicity. Thus, level 1 was considered the MTD and Level 0 was selected as the RD. Objective responses were seen in all patients. Conclusions: The RD is the level 0 dose, and this regimen is a feasible and well-tolerated regimen for the treatment of patients with Stage III NSCLC.« less

Inhaled corticosteroids and asthma control in adult-onset asthma: 12-year follow-up study.

PubMed

Vähätalo, Iida; Ilmarinen, Pinja; Tuomisto, Leena E; Niemelä, Onni; Kankaanranta, Hannu

2018-04-01

Prescribed inhaled corticosteroid (ICS) doses in asthma have been studied in cross-sectional settings whereas long-term follow-up studies have not been carried out. To evaluate prescribed medication longitudinally by calculating cumulative ICS doses and dose changes in a cohort of new-onset adult asthma during 12 years and in different groups of asthma control. A total of 203 patients were followed for 12 years as part of Seinäjoki Adult Asthma Study (SAAS). All asthma-related visits and prescribed medication over the study period were collected from medical records. Total cumulative ICS dose for the 12-year follow-up period was 3.4g (±SEM 0.1) per patient. Both respiratory specialists and GPs prescribed step-ups and step-downs in ICS treatment and in total 649 dose changes were noted during the follow-up (median 3(1-5) per patient). Patients with uncontrolled asthma received higher ICS doses throughout the follow-up period, and therefore, cumulative 12-year ICS dose (3.8g ± SEM 0.2) in this group was higher than that in those with partially controlled (3.4g ± SEM 0.2) or controlled disease (2.9g ± SEM 0.2) (p = 0.0001). Patients with uncontrolled asthma were also prescribed a higher number of ICS dose changes than patients with controlled disease. Despite frequent dose changes and high ICS doses during the 12-year follow-up, the level of asthma control remained poor in patients with uncontrolled asthma. This suggests that high ICS doses may not be effective enough for management of disease in patients with uncontrolled adult-onset asthma and novel targeted treatments are required. Copyright © 2018 Elsevier Ltd. All rights reserved.

Growth hormone (GH) effects on central fat accumulation in adult Japanese GH deficient patients: 6-month fixed-dose effects persist during second 6-month individualized-dose phase.

PubMed

Chihara, Kazuo; Shimatsu, Akira; Kato, Yuzuru; Kohno, Hitoshi; Tanaka, Toshiaki; Takano, Kazue; Irie, Minoru

2006-12-01

Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced abdominal obesity, which is associated with increased risk of cardiovascular complications. We investigated the effects of GH treatment in 27 adult Japanese GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD. Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a double-blind design and the dose was then individualized for each patient according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA) data were evaluated for percentages of trunk fat, total body fat and lean body mass. Serum IGF-I and lipid concentrations were determined at a central laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6 and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day, respectively. With the reductions in dose when individualized between weeks 24 and 48, mean serum IGF-I level was reduced and excessively high values, observed in AO patients on the fixed GH dose, were no longer seen. The decrease from baseline in trunk fat was similar at week 24 (-3.8 +/- 3.3%, p<0.001) and week 48 (-3.1 +/- 3.7%, p<0.001), and the difference between changes was not significant. Total cholesterol was decreased from baseline by -24 +/- 28 mg/dl (p<0.001) at week 24 and -17 +/- 28 mg/dl (p = 0.007) at week 48. Two patients had elevated HbA1c levels: one continued GH treatment after a dose reduction and the other discontinued due to persistent impaired glucose tolerance. Therefore, excessively high IGF-I levels can be avoided by individualized dosing during long-term GH treatment. Individualized dosing maintains the decrease in abdominal fat in adult Japanese GHD patients and should reduce the cardiovascular risk.

Population Pharmacokinetics of Enoxaparin in Pediatric Patients.

PubMed

Moffett, Brady S; Lee-Kim, YoungNa; Galati, Marianne; Mahoney, Donald; Shah, Mona D; Teruya, Jun; Yee, Donald

2018-02-01

There are no studies evaluating the pharmacokinetics of enoxaparin in the hospitalized pediatric patient population. To characterize the pharmacokinetics of enoxaparin in pediatric patients. A retrospective review of inpatients 1 to 18 years of age admitted to our institution who received enoxaparin with anti-factor Xa activity level monitoring was performed. Demographic variables, enoxaparin dosing, and anti-factor Xa activity levels were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. Simulation (n = 10 000) was performed to determine the percentage who achieved targeted anti-Xa levels at various doses. A total of 853 patients (male 52.1%, median age = 12.2 years; interquartile range [IQR] = 4.6-15.8 years) received a mean enoxaparin dose of 0.86 ± 0.31 mg/kg/dose. A median of 3 (IQR = 1-5) anti-factor Xa levels were sampled at 4.4 ± 1.3 hours after a dose, with a mean anti-factor Xa level of 0.52 ± 0.23 U/mL. A 1-compartment model best fit the data, and significant covariates included allometrically scaled weight, serum creatinine, and hematocrit on clearance, and platelets on volume of distribution. Simulations were run for patients both without and with reduced kidney function (creatinine clearance of ≤30 mL/min/1.73 m 2 ). A dose of 1 mg/kg/dose every 12 hours had the highest probability (72.3%) of achieving an anti-Xa level within the target range (0.5-1 U/mL), whereas a dose reduction of ~30% achieved the same result in patients with reduced kidney function. Pediatric patients should initially be dosed at 1-mg/kg/dose subcutaneously every 12 hours for treatment of thromboembolism followed by anti-Xa activity monitoring. Dose reductions of ~30% for creatinine clearance ≤30 mL/min/1.73 m 2 are required.

Computed Tomography Imaging of a Hip Prosthesis Using Iterative Model-Based Reconstruction and Orthopaedic Metal Artefact Reduction: A Quantitative Analysis.

PubMed

Wellenberg, Ruud H H; Boomsma, Martijn F; van Osch, Jochen A C; Vlassenbroek, Alain; Milles, Julien; Edens, Mireille A; Streekstra, Geert J; Slump, Cornelis H; Maas, Mario

To quantify the combined use of iterative model-based reconstruction (IMR) and orthopaedic metal artefact reduction (O-MAR) in reducing metal artefacts and improving image quality in a total hip arthroplasty phantom. Scans acquired at several dose levels and kVps were reconstructed with filtered back-projection (FBP), iterative reconstruction (iDose) and IMR, with and without O-MAR. Computed tomography (CT) numbers, noise levels, signal-to-noise-ratios and contrast-to-noise-ratios were analysed. Iterative model-based reconstruction results in overall improved image quality compared to iDose and FBP (P < 0.001). Orthopaedic metal artefact reduction is most effective in reducing severe metal artefacts improving CT number accuracy by 50%, 60%, and 63% (P < 0.05) and reducing noise by 1%, 62%, and 85% (P < 0.001) whereas improving signal-to-noise-ratios by 27%, 47%, and 46% (P < 0.001) and contrast-to-noise-ratios by 16%, 25%, and 19% (P < 0.001) with FBP, iDose, and IMR, respectively. The combined use of IMR and O-MAR strongly improves overall image quality and strongly reduces metal artefacts in the CT imaging of a total hip arthroplasty phantom.

Metabolic changes in serum steroids induced by total-body irradiation of female C57B/6 mice.

PubMed

Moon, Ju-Yeon; Shin, Hee-June; Son, Hyun-Hwa; Lee, Jeongae; Jung, Uhee; Jo, Sung-Kee; Kim, Hyun Sik; Kwon, Kyung-Hoon; Park, Kyu Hwan; Chung, Bong Chul; Choi, Man Ho

2014-05-01

The short- and long-term effects of a single exposure to gamma radiation on steroid metabolism were investigated in mice. Gas chromatography-mass spectrometry was used to generate quantitative profiles of serum steroid levels in mice that had undergone total-body irradiation (TBI) at doses of 0Gy, 1Gy, and 4Gy. Following TBI, serum samples were collected at the pre-dose time point and 1, 3, 6, and 9 months after TBI. Serum levels of progestins, progesterone, 5β-DHP, 5α-DHP, and 20α-DHP showed a significant down-regulation following short-term exposure to 4Gy, with the exception of 20α-DHP, which was significantly decreased at each of the time points measured. The corticosteroids 5α-THDOC and 5α-DHB were significantly elevated at each of the time points measured after exposure to either 1 or 4Gy. Among the sterols, 24S-OH-cholestoerol showed a dose-related elevation after irradiation that reached significance in the high dose group at the 6- and 9-month time points. Copyright © 2014 Elsevier Ltd. All rights reserved.

Natural radioactivity measurements and dosimetric evaluations in soil samples with a high content of NORM

NASA Astrophysics Data System (ADS)

Caridi, F.; Marguccio, S.; Durante, G.; Trozzo, R.; Fullone, F.; Belvedere, A.; D'Agostino, M.; Belmusto, G.

2017-01-01

In this article natural radioactivity measurements and dosimetric evaluations in soil samples contaminated by Naturally Occurring Radioactive Materials (NORM) are made, in order to assess any possible radiological hazard for the population and for workers professionally exposed to ionizing radiations. Investigated samples came from the district of Crotone, Calabria region, South of Italy. The natural radioactivity investigation was performed by high-resolution gamma-ray spectrometry. From the measured gamma spectra, activity concentrations were determined for 226Ra , 234-mPa , 224Ra , 228Ac and 40K and compared with their clearance levels for NORM. The total effective dose was calculated for each sample as due to the committed effective dose for inhalation and to the effective dose from external irradiation. The sum of the total effective doses estimated for all investigated samples was compared to the action levels provided by the Italian legislation (D.Lgs.230/95 and subsequent modifications) for the population members (0.3mSv/y) and for professionally exposed workers (1mSv/y). It was found to be less than the limit of no radiological significance (10μSv/y).

Iatrogenic radiation exposure to patients with early onset spine and chest wall deformities.

PubMed

Khorsand, Derek; Song, Kit M; Swanson, Jonathan; Alessio, Adam; Redding, Gregory; Waldhausen, John

2013-08-01

Retrospective cohort series. Characterize average iatrogenic radiation dose to a cohort of children with thoracic insufficiency syndrome (TIS) during assessment and treatment at a single center with vertically expandable prosthetic titanium rib. Children with TIS undergo extensive evaluations to characterize their deformity. No standardized radiographical evaluation exists, but all reports use extensive imaging. The source and level of radiation these patients receive is not currently known. We evaluated a retrospective consecutive cohort of 62 children who had surgical treatment of TIS at our center from 2001-2011. Typical care included obtaining serial radiographs, spine and chest computed tomographic (CT) scans, ventilation/perfusion scans, and magnetic resonance images. Epochs of treatment were divided into time of initial evaluation to the end of initial vertically expandable prosthetic titanium rib implantation with each subsequent epoch delineated by the next surgical intervention. The effective dose for each examination was estimated within millisieverts (mSv). Plain radiographs were calculated from references. Effective dose was directly estimated for CT scans since 2007 and an average of effective dose from 2007-2011 was used for scans before 2007. Effective dose from fluoroscopy was directly estimated. All doses were reported in mSv. A cohort of 62 children had a total of 447 procedures. There were a total of 290 CT scans, 4293 radiographs, 147 magnetic resonance images, and 134 ventilation/perfusion scans. The average accumulated effective dose was 59.6 mSv for children who had completed all treatment, 13.0 mSv up to initial surgery, and 3.2 mSv for each subsequent epoch of treatment. CT scans accounted for 74% of total radiation dose. Children managed for TIS using a consistent protocol received iatrogenic radiation doses that were on average 4 times the estimated average US background radiation exposure of 3 mSv/yr. CT scans comprised 74% of the total dose. 3.

PAEDIATRIC CT EXPOSURE PRACTICE IN THE COUNTY OF RIO DE JANEIRO: THE NEED TO ESTABLISH DIAGNOSTIC REFERENCE LEVELS.

PubMed

de Jesus, Fillipe M; Magalhães, Luis A G; Kodlulovich, Simone

2016-11-01

A pilot study of dose indicators in paediatric computed tomography (CT) was conducted to prove the need to establish diagnostic reference levels (DRLs) for the county of Rio de Janeiro. The dose descriptors were estimated from the beam dosimetry by applying the protocols used in each examination. The total patient sample included 279 children. Regarding the comparison of the dose-length product values among the hospitals, the high-resolution chest CT scans were distinguished among the three types of examinations, due to the discrepancies of 1148 % (1-5 y age group) and 2248 % (5-10 y age group) presented in Hospital A's dose-length product values relative to Hospital D's dose-length product values. The results showed that without DRL, the dose variation can be significant between hospitals in the same county for the same age group in the same examination. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of gamma-irradiation on the levels of total and cis/trans isomers of beta-carotene in dehydrated parsley

NASA Astrophysics Data System (ADS)

Sebastião, Kátia I.; Almeida-Muradian, Lígia B.; Romanelli, Maria Fernanda; Koseki, Paula Massae; Villavicencio, Anna Lúcia C. H.

2002-03-01

Ionizing radiation is a method for preservation of foods that use the high energy of gamma rays or accelerated electrons, thereby ionizing molecules. The most important precursor of vitamin A is β-carotene, a carotenoid with pro-vitamin A activity. The highly unsaturated chain confers the instability of β-carotene, and some reactions, as isomerisation, can reduce the characteristics of pro-vitamin A. The present study investigated whether increasing doses of 0, 10 and 20 kGy lower the total β-carotene level and if an enhancement of cis-isomers occurred on samples of dehydrated parsley. No differences were observed of either fractions analyzed at doses applied in this study, nor did it contribute to the decrease of vitamin A.

The role of red dragon fruit peel (Hylocereus polyrhizus) to improvement blood lipid levels of hyperlipidaemia male mice

NASA Astrophysics Data System (ADS)

Hernawati; Setiawan, N. A.; Shintawati, R.; Priyandoko, D.

2018-05-01

The purpose of this research was to know the role of red dragon fruit peel powder to total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and weight in the male hyperlipidaemic Balb-C mice (Mus musculus). This study used a completely randomized design (CRD) and four replicates for each dose treatments. Samples were 24 male mice that divided into six groups i.e. positive and negative controls, doses of 50; 100; 150 and 200 mg/kgBW/days red dragon fruit peel powder. Before being given treatment, mice were given feed containing high fat for 20 days until experiencing conditions hyperlipidaemia. The red dragon fruit peel powder was given at oral with used gavage for 30 days. Blood samples were taken from the tail on vena caudalis. Blood lipid samples were analysed at enzymatic with BIOLABO kits. The results of this study indicate that after administration of red dragon fruit peel powder total cholesterol levels, triglycerides and LDL-c decreased, along with increasing doses of red dragon fruit peel powder for 30 days. Furthermore showed that dragon fruit powder can increase HDL-c levels. The conclusion of this research was The red dragon fruit peel powder can improve blood lipid level of male Balb-c mice hyperlipidaemia.

Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non-small cell lung cancer

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

Martin, Kate L.; Gomez, Jorge; Nazareth, Daryl P.

2012-07-01

To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectivelymore » for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit.« less

Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats

PubMed Central

Omidi, Arash; Riahinia, Narges; Montazer Torbati, Mohammad Bagher; Behdani, Mohammad-Ali

2014-01-01

Objectives: Acetaminophen (APAP) toxicity is known to be common and potentially fatal. This study aims to investigate the protective effects of hydroalcoholic extract, remaining from Crocus sativus petals (CSP) against APAP-induced hepatotoxicity by measuring the blood parameters and studying the histopathology of liver in male rats. Materials and Methods: Wister rats (24) were randomly assigned into four groups including: I) healthy, receiving normal saline; II) Intoxicated, receiving only APAP (600 mg/kg); III) pre-treated with low dose of CSP (10 mg /kg) and receiving APAP (600 mg/kg); IV) pre-treated with high dose of CSP (20 mg/kg) and receiving APAP (600 mg/kg). Results: The APAP treatment resulted in higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin, along with lower total protein and albumin concentration than the control group. The administration of CSP with a dose of 20 mg/kg was found to result in lower levels of AST, ALT and bilirubin, with a significant higher concentration of total protein and albumin. The histopathological results regarding liver pathology, revealed sever conditions including cell swelling, severe inflammation and necrosis in APAP-exposed rats, which was quiet contrasting compared to the control group. The pre-treated rats with low doses of ‍CSP showed hydropic degeneration with mild necrosis in centrilobular areas of the liver, while the same subjects with high doses of ‍CSP appeared to have only mild hepatocyte degeneration. Conclusions: Doses of 20 mg/kg of CSP ameliorates APAP–induced acute liver injury in rats. It was concluded that the antioxidant property of CSP resulted in reducing the oxidative stress complications of toxic levels of APAP in intoxicated rats. PMID:25386395

Bacterial extract (OM-85) with human-equivalent doses does not inhibit the development of asthma in a murine model.

PubMed

Rodrigues, A; Gualdi, L P; de Souza, R G; Vargas, M H M; Nuñez, N K; da Cunha, A A; Jones, M H; Pinto, L A; Stein, R T; Pitrez, P M

OM-85 is an immunostimulant bacterial lysate, which has been proven effective in reducing the number of lower airways infections. We investigated the efficacy of the bacterial lysate OM-85 in the primary prevention of a murine model of asthma. In the first phase of our study the animals received doses of 0.5μg, 5μg and 50μg of OM-85 through gavage for five days (days -10 to -6 of the protocol), 10 days prior to starting the sensitisation with ovalbumin (OVA), in order to evaluate the results of dose-response protocols. A single dose (5μg) was then chosen in order to verify in detail the effect of OM-85 on the pulmonary allergic response. Total/differential cells count and cytokine levels (IL-4, IL-5, IL-13 and IFN-γ) from bronchoalveolar lavage fluid (BALF), OVA-specific IgE levels from serum, lung function and lung histopathological analysis were evaluated. OM-85 did not reduce pulmonary eosinophilic response, regardless of the dose used. In the phase protocol using 5μg/animal of OM-85, no difference was shown among the groups studied, including total cell and eosinophil counts in BALF, serum OVA-specific IgE, lung histopathologic findings and lung resistance. However, OM-85 decreased IL-5 and IL-13 levels in BALF. OM-85, administered in early life in mice in human-equivalent doses, does not inhibit the development of allergic pulmonary response in mice. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Exploring Radiotherapy Targeting Strategy and Dose: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III Non-Small Cell Lung Cancer.

PubMed

Schild, Steven E; Fan, Wen; Stinchcombe, Thomas E; Vokes, Everett E; Ramalingam, Suresh S; Bradley, Jeffrey D; Kelly, Karen; Pang, Herbert H; Wang, Xiaofei

2018-04-21

Concurrent chemoradiotherapy(CRT) is standard therapy for locally-advanced non-small-cell lung cancer(LA-NSCLC)patients. This study was performed to examine thoracic radiotherapy(TRT) parameters and their impact on patient survival. We collected Individual patient data(IPD) from 3600LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy(elective nodal irradiation(ENI) compared to involved field TRT(IF-TRT)), total dose, and biologically effective dose(BED). Hazard ratios(HRs) for overall survival were calculated with univariable and multivariable Cox models. TRT doses ranged from 60 to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT(univariable HR,1.37;95%CI,1.24-1.51,p<0.0001;multivariable HR,1.31;95%CI,1.08-1.59,p=0.002). The median survival of the IF and ENI patients were 24 and 16 months, respectively. Patients were divided into 3 dose groups: low total dose(60 Gy), medium total dose(>60Gy-66Gy) and high total dose(>66Gy-74 Gy). With reference to the low dose group, the multivariable HR's were 1.08 for the medium dose group(95%CI=0.93-1.25) and 1.12 for the high dose group(CI=0.97-1.30).The univariate p=0.054 and multivariable p=0.17. BED was grouped as follows: low(<55.5Gy 10 ), medium(=55.5 Gy 10) , or high(>55.5 Gy 10 ). With reference to the low BED group, the HR was 1.00(95%CI=0.85-1.18) for the medium BED group and 1.10(95%CI=0.93-1.31) for the high BED group. The univariable p=0.076 and multivariable p=0.16. For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT. Copyright © 2018. Published by Elsevier Inc.

Chemical and toxicological evaluation of methanol extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed on hematological parameters and hepatorenal functions in mice.

PubMed

Mazumder, Upal Kanti; Gupta, Malaya; Pal, Dilipkumar; Bhattacharya, Shiladitya

2003-01-01

Methanol extract of Cuscuta reflexa Roxb. stem (MECR) contain flavonoids (0.2%) and Corchorus olitorius Linn. seed (MECO) was found to contain steroids and cardenolide glycosides. Effects of multiple weekly dose of MECR (25, 50, 75 mg/kg, i.p.) and MECO (15, 20, 25 mg/kg, i.p.) on liver and kidney functions and hematological parameters in mice were studied. No significant alteration of RBC count and hemoglobin content was observed in all dose level of treatment in MECR and MECO treated mice whereas significant increase of clotting time was seen in moderate and high doses in both case. MECR and MECO both caused significant increase in WBC count only in high dose level of treatment. Both the extracts in medium and high dose level increased SGOT, SGPT, NPN and plasma cholesterol significantly. Serum alkaline phosphatase and total bilirubin were also increased by both moderate and high dose level of treatments in MECR and MECO treated mice respectively. Low dose of both the extract did not exhibit any significant change of creatinine and serum protein level. But high dose level of MECR and MECO significantly increased creatinine level. Increase in plasma cholesterol may be due to decrease in cholesterol catabolism owing to liver dysfunction of due to the intake of MECO itself as it was found to be steroid in nature. Elevated level of SGOT, SGPT and serum alkaline phosphatase activity in moderate and high dose level of weekly treated mice may be due to improper liver function following the treatment. Increased urea, non protein nitrogen and creatinine content in blood have been observed with impaired renal function. The slightly higher toxicity in case of MECO treated mice may be due to the presence of cardenolide glycosides in the ME of C. olitorius seed. However, low doses of MECR and MECO (25 and 15 mg/kg, i.p. respectively) did not exhibit any remarkable change on liver and kidney functions and hematological parameters.

Dose-specific transcriptional responses in thyroid tissue in mice after (131)I administration.

PubMed

Rudqvist, Nils; Schüler, Emil; Parris, Toshima Z; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2015-03-01

In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after (131)I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with (131)I exposure in normal mouse thyroid tissue and 2) propose biomarkers for (131)I exposure of the thyroid. Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of (131)I and killed 24h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. In total, 497, 546, and 90 transcripts were regulated (fold change ≥1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to (131)I exposure of thyroid. During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low, intermediate, and high absorbed doses from (131)I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to (131)I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology. This work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread. Copyright © 2014 Elsevier Inc. All rights reserved.

Contrast Dose and Radiation Dose Reduction in Abdominal Enhanced Computerized Tomography Scans with Single-phase Dual-energy Spectral Computerized Tomography Mode for Children with Solid Tumors

PubMed Central

Yu, Tong; Gao, Jun; Liu, Zhi-Min; Zhang, Qi-Feng; Liu, Yong; Jiang, Ling; Peng, Yun

2017-01-01

Background: Contrast dose and radiation dose reduction in computerized tomography (CT) scan for adult has been explored successfully, but there have been few studies on the application of low-concentration contrast in pediatric abdominal CT examinations. This was a feasibility study on the use of dual-energy spectral imaging and adaptive statistical iterative reconstruction (ASiR) for the reduction of radiation dose and iodine contrast dose in pediatric abdominal CT patients with solid tumors. Methods: Forty-five patients with solid tumors who had initial CT (Group B) and follow-up CT (Group A) after chemotherapy were enrolled. The initial diagnostic CT scan (Group B) was performed using the standard two-phase enhanced CT with 320 mgI/ml concentration contrast, and the follow-up scan (Group A) was performed using a single-phase enhanced CT at 45 s after the beginning of the 270 mgI/ml contrast injection using spectral mode. Forty percent ASiR was used for the images in Group B and monochromatic images with energy levels ≥60 keV in Group A. In addition, filtered back-projection (FBP) reconstruction was used for monochromatic images <60 keV in Group A. The total radiation dose, total iodine load, contrast injection speed, and maximum injection pressure were compared between the two groups. The 40 keV and 60 keV spectral CT images of Group A were compared with the images of Group B to evaluate overall image quality. Results: The total radiation dose, total iodine load, injection speed, and maximum injection pressure for Group A were decreased by 19%, 15%, 34.4%, and 18.3%, respectively. The optimal energy level in spectral CT for displaying the abdominal vessels was 40 keV. At this level, the CT values in the abdominal aorta and its three branches, the portal vein and its two branches, and the inferior vena cava were all greater than 340 hounsfield unit (HU). The abdominal organs of Groups A and B had similar degrees of absolute and relative enhancement (t = 0.36 and −1.716 for liver, −0.153 and −1.546 for pancreas, and 2.427 and 0.866 for renal cortex, all P > 0.05). Signal-to-noise ratio of the abdominal organs was significantly lower in Group A than in Group B (t = −8.11 for liver, −7.83 for pancreas, and −5.38 for renal cortex, all P < 0.05). However, the subjective scores for the 40 keV (FBP) and 60 keV (40% ASiR) spectral CT images determined by two radiologists were all >3, indicating clinically acceptable image quality. Conclusions: Single-phase, dual-energy spectral CT used for children with solid abdominal tumors can reduce contrast dose and radiation dose and can also maintain clinically acceptable image quality. PMID:28345547

Contrast Dose and Radiation Dose Reduction in Abdominal Enhanced Computerized Tomography Scans with Single-phase Dual-energy Spectral Computerized Tomography Mode for Children with Solid Tumors.

PubMed

Yu, Tong; Gao, Jun; Liu, Zhi-Min; Zhang, Qi-Feng; Liu, Yong; Jiang, Ling; Peng, Yun

2017-04-05

Contrast dose and radiation dose reduction in computerized tomography (CT) scan for adult has been explored successfully, but there have been few studies on the application of low-concentration contrast in pediatric abdominal CT examinations. This was a feasibility study on the use of dual-energy spectral imaging and adaptive statistical iterative reconstruction (ASiR) for the reduction of radiation dose and iodine contrast dose in pediatric abdominal CT patients with solid tumors. Forty-five patients with solid tumors who had initial CT (Group B) and follow-up CT (Group A) after chemotherapy were enrolled. The initial diagnostic CT scan (Group B) was performed using the standard two-phase enhanced CT with 320 mgI/ml concentration contrast, and the follow-up scan (Group A) was performed using a single-phase enhanced CT at 45 s after the beginning of the 270 mgI/ml contrast injection using spectral mode. Forty percent ASiR was used for the images in Group B and monochromatic images with energy levels ≥60 keV in Group A. In addition, filtered back-projection (FBP) reconstruction was used for monochromatic images <60 keV in Group A. The total radiation dose, total iodine load, contrast injection speed, and maximum injection pressure were compared between the two groups. The 40 keV and 60 keV spectral CT images of Group A were compared with the images of Group B to evaluate overall image quality. The total radiation dose, total iodine load, injection speed, and maximum injection pressure for Group A were decreased by 19%, 15%, 34.4%, and 18.3%, respectively. The optimal energy level in spectral CT for displaying the abdominal vessels was 40 keV. At this level, the CT values in the abdominal aorta and its three branches, the portal vein and its two branches, and the inferior vena cava were all greater than 340 hounsfield unit (HU). The abdominal organs of Groups A and B had similar degrees of absolute and relative enhancement (t = 0.36 and -1.716 for liver, -0.153 and -1.546 for pancreas, and 2.427 and 0.866 for renal cortex, all P> 0.05). Signal-to-noise ratio of the abdominal organs was significantly lower in Group A than in Group B (t = -8.11 for liver, -7.83 for pancreas, and -5.38 for renal cortex, all P< 0.05). However, the subjective scores for the 40 keV (FBP) and 60 keV (40% ASiR) spectral CT images determined by two radiologists were all> 3, indicating clinically acceptable image quality. Single-phase, dual-energy spectral CT used for children with solid abdominal tumors can reduce contrast dose and radiation dose and can also maintain clinically acceptable image quality.

Effect of gamma irradiation on some physicochemical properties and bioactive compounds of jujube (Ziziphus jujuba var vulgaris) fruit

NASA Astrophysics Data System (ADS)

Najafabadi, Najmeh Shams; Sahari, Mohammad Ali; Barzegar, Mohsen; Esfahani, Zohreh Hamidi

2017-01-01

Interest in the protection of bioactive compounds and a safe alternative method for preservation of processed fruits and fruit juices has recently increased significantly throughout the world. There is a distinct lack of information on the profile of bioactive compounds in jujube fruit (e.g. organic acids, anthocyanins, and water-soluble vitamins) and their changes during processing (e.g. gamma irradiation). Therefore, in this study, the effect of gamma irradiation at different doses (0.0, 0.5, 1.0, 2.5 and 5.0 kGy) on some physicochemical properties and the bioactive compounds of jujube fruit was investigated. The total soluble solids (TSSs) values remained unaffected at various doses, while the level of total acidity (TA) showed a slight increase at doses ≥ 2.5 kGy (p ≤ 0.05). Irradiation up to 2.5 kGy caused a significant increase in the total monomeric anthocyanin and the total phenolic content (about 12% and 6%, respectively), but a significant decrease was observed in both parameters immediately after irradiation at 5 kGy. Moreover, irradiation treatment caused a significant decrease in L* value and a significant increase in a* and b* values (P ≤ 0.05); however, changes of color were slight until the dose of 5 kGy. Gamma irradiation up to 2.5 kGy had no significant effect on the concentration of malic, citric and succinic acids, while the level of ascorbic acid decreased significantly at all irradiation doses (0-5 kGy). Cyanidin-3, 5-diglucoside was determined as the major anthocyanin in the jujube fruit studied (about 68%), which was reduced significantly when 5 kGy of irradiation was applied (degradation percentage: 27%). The results demonstrated that vitamins C, B2 and B1 are the most water-soluble vitamins in jujube fruit, respectively. Vitamins C and B1 content significantly decreased at all applied doses (0-5 kGy), whereas B2 content at doses ≤ 2.5 kGy was not significantly affected. The results of this study indicate that gamma irradiation at doses below 2.5 kGy can be successfully used for improving the quality the jujube fruit.

Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.

PubMed

Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; McFaline, Jose; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T; Greenberger, Joel S; Samson, Leona D; Dedon, Peter C; Yanch, Jacquelyn C; Engelward, Bevin P

2012-08-01

In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break-induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.

Performance comparison between total variation (TV)-based compressed sensing and statistical iterative reconstruction algorithms.

PubMed

Tang, Jie; Nett, Brian E; Chen, Guang-Hong

2009-10-07

Of all available reconstruction methods, statistical iterative reconstruction algorithms appear particularly promising since they enable accurate physical noise modeling. The newly developed compressive sampling/compressed sensing (CS) algorithm has shown the potential to accurately reconstruct images from highly undersampled data. The CS algorithm can be implemented in the statistical reconstruction framework as well. In this study, we compared the performance of two standard statistical reconstruction algorithms (penalized weighted least squares and q-GGMRF) to the CS algorithm. In assessing the image quality using these iterative reconstructions, it is critical to utilize realistic background anatomy as the reconstruction results are object dependent. A cadaver head was scanned on a Varian Trilogy system at different dose levels. Several figures of merit including the relative root mean square error and a quality factor which accounts for the noise performance and the spatial resolution were introduced to objectively evaluate reconstruction performance. A comparison is presented between the three algorithms for a constant undersampling factor comparing different algorithms at several dose levels. To facilitate this comparison, the original CS method was formulated in the framework of the statistical image reconstruction algorithms. Important conclusions of the measurements from our studies are that (1) for realistic neuro-anatomy, over 100 projections are required to avoid streak artifacts in the reconstructed images even with CS reconstruction, (2) regardless of the algorithm employed, it is beneficial to distribute the total dose to more views as long as each view remains quantum noise limited and (3) the total variation-based CS method is not appropriate for very low dose levels because while it can mitigate streaking artifacts, the images exhibit patchy behavior, which is potentially harmful for medical diagnosis.

Radiological dose in Muria peninsula from SB-LOCA event

NASA Astrophysics Data System (ADS)

Sunarko; Suud, Zaki

2017-01-01

Dose assessment for accident condition is performed for Muria Peninsula region using source-term from Three-Mile Island unit 2 SB-LOCA accident. Xe-133, Kr-88, 1-131 and Cs-137 isotopes are considered in the calculation. The effluent is assumed to be released from a 50 m stack. Lagrangian particle dispersion method (LPDM) employing non-Gaussian dispersion coefficient in 3-dimensional mass-consistent wind-field is employed to obtain periodic surface-level concentration which is then time-integrated to obtain spatial distribution of ground-level dose. In 1-hour simulation, segmented plumes with 60 seconds duration with a total of 18.000 particles involved. Simulations using 6-hour worst-case meteorological data from Muria peninsula results in a peak external dose of around 1.668 mSv for low scenario and 6.892 mSv for high scenario in dry condition. In wet condition with 5 mm/hour and 10 mm/hour rain for the whole duration of the simulation provides only minor effect to dose. The peak external dose is below the regulatory limit of 50 mSv for effective skin dose from external gamma exposure.

Comparing Single species Toxicity Tests to Mesocosm Community-Level Responses to Total Dissolved Solids Comprised of Different Major Ions

EPA Science Inventory

Total Dissolved Solids (TDS) dosing studies representing different sources of ions were conducted from 2011-2015. Emergence responses in stream mesocosms were compared to single-species exposures using a whole effluent testing (WET) format and an ex-situ method (single species te...

PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

PubMed

Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

2015-09-01

Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

NASA Technical Reports Server (NTRS)

Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

Abdominal Pediatric Cancer Surveillance using Serial CT: Evaluation of Organ Absorbed Dose and Effective Dose

PubMed Central

Lam, Diana; Wootton-Gorges, Sandra L.; McGahan, John P.; Stern, Robin; Boone, John M.

2012-01-01

Computed tomography (CT) is used extensively in cancer diagnosis, staging, evaluation of response to treatment, and in active surveillance for cancer reoccurrence. A review of CT technology is provided, at a level of detail appropriate for a busy clinician to review. The basis of x-ray CT dosimetry is also discussed, and concepts of absorbed dose and effective dose are distinguished. Absorbed dose is a physical quantity (measured in milliGray) equal to the x-ray energy deposited in a mass of tissue, whereas effective dose utilizes an organ-specific weighting method which converts organ doses to effective dose measured in milliSieverts. The organ weighting values carry with them a measure of radiation risk, and so effective dose (in mSv) is not a physical dose metric but rather is one that conveys radiation risk. The use of CT in a cancer surveillance protocol was used as an example of a pediatric patient who had kidney cancer, with surgery and radiation therapy. The active use of CT for cancer surveillance along with diagnostic CT scans led to a total of 50 CT scans performed on this child in a 7 year period. It was estimated that the patient received an average organ dose of 431 mGy from these CT scans. By comparison, the radiation therapy was performed and delivered 50.4 Gy to the patient’s abdomen. Thus, the total dose from CT represented only 0.8% of the patients radiation dose. PMID:21362521

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

PubMed Central

Osipov, A. N.; Klokov, D. Y.; Elakov, A. L.; Rozanova, O. M.; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

2004-01-01

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20–61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level γ-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation. PMID:19330145

Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine.

PubMed

Cardell, Kristina; Akerlind, Britt; Sällberg, Matti; Frydén, Aril

2008-08-01

Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs) and are considered to be nonresponders. A total of 48 nonresponders and 20 subjects naive to the HBV vaccine received a double dose of combined hepatitis A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and 1 month after each dose. Among 44 nonresponders, protective anti-HBs levels were found in 26 (59%) after the first dose and in 42 (95%) after the third dose. Among the control subjects, the corresponding figures were 10% and 100%, respectively. All subjects seroconverted to anti-HAV. The titers of both anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P< .01). Revaccination of nonresponders to the standard hepatitis B vaccine regimen with a double dose of the combined hepatitis A and B vaccine was highly effective. This is most likely explained by the increased dose, a positive bystander effect conferred by the hepatitis A vaccine, or both.

Radiation exposure in transcatheter patent ductus arteriosus closure: time to tune?

PubMed

Villemain, Olivier; Malekzadeh-Milani, Sophie; Sitefane, Fidelio; Mostefa-Kara, Meriem; Boudjemline, Younes

2018-05-01

The aims of this study were to describe radiation level at our institution during transcatheter patent ductus arteriosus occlusion and to evaluate the components contributing to radiation exposure. Transcatheter occlusion relying on X-ray imaging has become the treatment of choice for patients with patent ductus arteriosus. Interventionists now work hard to minimise radiation exposure in order to reduce risk of induced cancers. We retrospectively reviewed all consecutive children who underwent transcatheter closure of patent ductus arteriosus from January 2012 to January 2016. Clinical data, anatomical characteristics, and catheterisation procedure parameters were reported. Radiation doses were analysed for the following variables: total air kerma, mGy; dose area product, Gy.cm2; dose area product per body weight, Gy.cm2/kg; and total fluoroscopic time. A total of 324 patients were included (median age=1.51 [Q1-Q3: 0.62-4.23] years; weight=10.3 [6.7-17.0] kg). In all, 322/324 (99.4%) procedures were successful. The median radiation doses were as follows: total air kerma: 26 (14.5-49.3) mGy; dose area product: 1.01 (0.56-2.24) Gy.cm2; dose area product/kg: 0.106 (0.061-0.185) Gy.cm2/kg; and fluoroscopic time: 2.8 (2-4) min. In multivariate analysis, a weight >10 kg, a ductus arteriosus width <2 mm, complications during the procedure, and a high frame rate (15 frames/second) were risk factors for an increased exposure. Lower doses of radiation can be achieved with subsequent recommendations: technical improvement, frame rate reduction, avoidance of biplane cineangiograms, use of stored fluoroscopy as much as possible, and limitation of fluoroscopic time. A greater use of echocardiography might even lessen the exposure.

Inactivation of contaminated fungi and antioxidant effects of peach ( Prunus persica L. Batsch cv Dangeumdo) by 0.5-2 kGy gamma irradiation

NASA Astrophysics Data System (ADS)

Kim, Kyoung-Hee; Kim, Mi-Seon; Kim, Hong-Gi; Yook, Hong-Sun

2010-04-01

The effect of gamma irradiation (0.5-2 kGy) on the physicochemical properties of peaches was investigated during a 6-day storage at 20±3 °C. Gamma irradiation is able to inactivate the four pathogens, namely Botrytis cinerea, Penicillium expansum, Rhizopus stolonifer var. stolonifer and Monilinia fructicola in peaches. Hardness significantly decreased with the increment of irradiation dose level whereas soluble solid and total polyphenol contents increased with increment of irradiation dose level. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity of the irradiated peach was higher than that of control, and its activity increased with increment of irradiation dose level. These results suggest that gamma irradiation of peaches improved antioxidant activity, but dramatically affects the hardness throughout the entire storage time.

Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease*.

PubMed

Marwali, Eva M; Boom, Cindy E; Sakidjan, Indriwanto; Santoso, Anwar; Fakhri, Dicky; Kartini, Ay; Kekalih, Aria; Schwartz, Steven M; Haas, Nikolaus A

2013-09-01

This study was conducted to determine if oral triiodothyronine supplementation could prevent the decrease of serum triiodothyronine levels that commonly occurs after cardiopulmonary bypass for pediatric congenital heart surgery. Secondary objectives included identifying any significant adverse effects of oral triiodothyronine supplementation, including any effects on the thyroid/pituitary axis. Randomized, placebo-controlled, doubleblind clinical trial Operating room and ICU. Infants and children younger than 2 years of age undergoing congenital heart surgery using cardiopulmonary bypass (n = 43). Subjects were assigned to placebo (n = 15, group A) or one of two treatment groups: a low-dose group (group B, n = 14, 0.5 mcg/kg triiodothyronine orally every 24 hr for 3 d) or a high-dose group (group C, n = 14, 0.5 mcg/kg triiodothyronine orally every 12 hr for 3 d). Thyroid hormone, including total and free triiodothyronine levels at predetermined time points, potential side effects indicating hyperthyroidism, indicators of the thyroid-pituitary axis, and clinical endpoints. Oral triiodothyronine supplementation twice-daily maintained serum triiodothyronine levels within normal limits in group C, whereas serum levels progressively declined in groups A and B. A statistically significant difference in triiodothyronine levels between the treatment groups occurred between 18 and 36 hours post cross-clamp release, with the largest difference in serum levels between group C and group A noted at 36 hours post cross-clamp release (total triiodothyronine, 0.71 ± 0.15 [0.34-1.08] ng/mL [p < 0.01]; free triiodothyronine, 2.56 ± 0.49 [1.33-3.79] pg/mL [p < 0.01]). There was no evidence of hyperthyroidism or suppression of the pituitary-thyroid axis in either treatment group Oral triiodothyronine supplementation at a dose of 0.5 mcg/kg every 12 hours for 3 days can maintain total and free triiodothyronine levels within normal limits after open-heart surgery using cardiopulmonary bypass for congenital heart disease.

Variability in CT lung-nodule quantification: Effects of dose reduction and reconstruction methods on density and texture based features.

PubMed

Lo, P; Young, S; Kim, H J; Brown, M S; McNitt-Gray, M F

2016-08-01

To investigate the effects of dose level and reconstruction method on density and texture based features computed from CT lung nodules. This study had two major components. In the first component, a uniform water phantom was scanned at three dose levels and images were reconstructed using four conventional filtered backprojection (FBP) and four iterative reconstruction (IR) methods for a total of 24 different combinations of acquisition and reconstruction conditions. In the second component, raw projection (sinogram) data were obtained for 33 lung nodules from patients scanned as a part of their clinical practice, where low dose acquisitions were simulated by adding noise to sinograms acquired at clinical dose levels (a total of four dose levels) and reconstructed using one FBP kernel and two IR kernels for a total of 12 conditions. For the water phantom, spherical regions of interest (ROIs) were created at multiple locations within the water phantom on one reference image obtained at a reference condition. For the lung nodule cases, the ROI of each nodule was contoured semiautomatically (with manual editing) from images obtained at a reference condition. All ROIs were applied to their corresponding images reconstructed at different conditions. For 17 of the nodule cases, repeat contours were performed to assess repeatability. Histogram (eight features) and gray level co-occurrence matrix (GLCM) based texture features (34 features) were computed for all ROIs. For the lung nodule cases, the reference condition was selected to be 100% of clinical dose with FBP reconstruction using the B45f kernel; feature values calculated from other conditions were compared to this reference condition. A measure was introduced, which the authors refer to as Q, to assess the stability of features across different conditions, which is defined as the ratio of reproducibility (across conditions) to repeatability (across repeat contours) of each feature. The water phantom results demonstrated substantial variability among feature values calculated across conditions, with the exception of histogram mean. Features calculated from lung nodules demonstrated similar results with histogram mean as the most robust feature (Q ≤ 1), having a mean and standard deviation Q of 0.37 and 0.22, respectively. Surprisingly, histogram standard deviation and variance features were also quite robust. Some GLCM features were also quite robust across conditions, namely, diff. variance, sum variance, sum average, variance, and mean. Except for histogram mean, all features have a Q of larger than one in at least one of the 3% dose level conditions. As expected, the histogram mean is the most robust feature in their study. The effects of acquisition and reconstruction conditions on GLCM features vary widely, though trending toward features involving summation of product between intensities and probabilities being more robust, barring a few exceptions. Overall, care should be taken into account for variation in density and texture features if a variety of dose and reconstruction conditions are used for the quantification of lung nodules in CT, otherwise changes in quantification results may be more reflective of changes due to acquisition and reconstruction conditions than in the nodule itself.

Electronic Subsystem Analysis (ESA)

DTIC Science & Technology

1977-01-01

than aluminum for the gate material, 0 Ion implanted source and draia regions, 0 Dielectrically isolated transistors. The use of a doped polysilicon gate...second level of interconnect ( polysilicon ). Ion implantation is essentially a precisely controllable pre-deposition of the required dopants. It’s use...discussed below). Radiation effects on MOS devices include the following: 0 Total Dose ol Dose Rate o Neutrons Because MOS technology is based on

Comparison of the effects of high-dose atorvastatin and high-dose rosuvastatin on oxidative stress in patients with acute myocardial infarction: A pilot study.

PubMed

Kilit, Celal; Koçak, Fatma Emel; Paşalı Kilit, Türkan

2017-04-01

Oxidative stress is increased in patients with acute myocardial infarction (AMI). Statins reduce oxidative stress independent of their effect in reducing low-density lipoprotein cholesterol (LDL-C). The aim of the present study was to compare the effects of atorvastatin and rosuvastatin on oxidative status by investigating serum paraoxonase, serum arylesterase, total oxidant status, total antioxidant status (TAS) and oxidative stress index (OSI) in patients with AMI. Seventy patients with AMI were randomized into 2 groups; total of 55 patients (19 females, 36 males) aged 32 to 86 years completed the study and were included in the analysis. Patients were treated with 80 mg atorvastatin or 40 mg rosuvastatin for 4 weeks. Lipid parameters and parameters of oxidative status were measured at admission and after 4-week statin treatment. After 4-week treatment, atorvastatin and rosuvastatin were associated with significant reduction in TAS, OSI, total cholesterol, and LDL-C levels. Serum paraoxonase level was significantly increased in both groups, while high-density lipoprotein cholesterol (HDL-C) level was significantly reduced in atorvastatin group. No statistically significant differences were found between atorvastatin and rosuvastatin in terms of actual difference in oxidative stress parameters. Atorvastatin and rosuvastatin have similar effects on oxidative status in patients with AMI. Rosuvastatin affected HDL-C level more favorably than atorvastatin.

A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

NASA Astrophysics Data System (ADS)

Osman, N. D.; Shamsuri, S. B. M.; Tan, Y. W.; Razali, M. A. S. M.; Isa, S. M.

2017-05-01

Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDIvol and CTDIw) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDIw ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients.

Charge Yield at Low Electric Fields: Considerations for Bipolar Integrated Circuits

NASA Technical Reports Server (NTRS)

Johnston, A. H.; Swimm, R. T.; Thorbourn, D. O.

2013-01-01

A significant reduction in total dose damage is observed when bipolar integrated circuits are irradiated at low temperature. This can be partially explained by the Onsager theory of recombination, which predicts a strong temperature dependence for charge yield under low-field conditions. Reduced damage occurs for biased as well as unbiased devices because the weak fringing field in thick bipolar oxides only affects charge yield near the Si/SiO2 interface, a relatively small fraction of the total oxide thickness. Lowering the temperature of bipolar ICs - either continuously, or for time periods when they are exposed to high radiation levels - provides an additional degree of freedom to improve total dose performance of bipolar circuits, particularly in space applications.

SU-F-I-09: Improvement of Image Registration Using Total-Variation Based Noise Reduction Algorithms for Low-Dose CBCT

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

Mukherjee, S; Farr, J; Merchant, T

Purpose: To study the effect of total-variation based noise reduction algorithms to improve the image registration of low-dose CBCT for patient positioning in radiation therapy. Methods: In low-dose CBCT, the reconstructed image is degraded by excessive quantum noise. In this study, we developed a total-variation based noise reduction algorithm and studied the effect of the algorithm on noise reduction and image registration accuracy. To study the effect of noise reduction, we have calculated the peak signal-to-noise ratio (PSNR). To study the improvement of image registration, we performed image registration between volumetric CT and MV- CBCT images of different head-and-neck patientsmore » and calculated the mutual information (MI) and Pearson correlation coefficient (PCC) as a similarity metric. The PSNR, MI and PCC were calculated for both the noisy and noise-reduced CBCT images. Results: The algorithms were shown to be effective in reducing the noise level and improving the MI and PCC for the low-dose CBCT images tested. For the different head-and-neck patients, a maximum improvement of PSNR of 10 dB with respect to the noisy image was calculated. The improvement of MI and PCC was 9% and 2% respectively. Conclusion: Total-variation based noise reduction algorithm was studied to improve the image registration between CT and low-dose CBCT. The algorithm had shown promising results in reducing the noise from low-dose CBCT images and improving the similarity metric in terms of MI and PCC.« less

Anxiogenic effects of chronic exposure to nandrolone decanoate (ND) at supraphysiological dose in rats: a brief report.

PubMed

Rosic, Gvozden; Joksimovic, Jovana; Selakovic, Dragica; Milovanovic, Dragan; Jakovljevic, Vladimir

2014-01-01

Nandrolone decanoate (ND) is frequently used anabolic androgenic steroid (AAS) among the athletes. Despite the health risks, there is significant increase in prevalence of AAS abuse. The aim of this study was to investigate the effects of chronic exposure to ND at supraphysiological dose (to mimic the doses for human AAS abusers) on anxiety levels in adult rats. We performed several behavioral tests (open field test, elevated plus maze test, beam-walking test, evoked beam-walking test and tail suspension test) for estimation of anxiety in rats. Adult rats received 20 mg/kg intraperitoneal injection of ND weekly for four weeks. Behavioral test were performed on the seventh day after the last dose of ND. Anxiogenic-like pattern of behavior was clearly observed in several behavioral tests, such as open field test (decrease of total distance moved and cumulative duration of moving, decrease of an average velocity of the animals, decrease of frequency and total time in centre zone); elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze); evoked beam-walking test (decreased time to cross the beam) and tail suspension test (increased latency to first immobility and decreased total duration of immobility). Results of this study show that four-week treatment with the supraphysiological dose of ND produced anxiogenic effects in sedentary male rats. Our results show that rats after chronic treatment with a supraphysiological dose of ND exhibited anxiety-like behavior.

Valeriana wallichii root extract improves sleep quality and modulates brain monoamine level in rats.

PubMed

Sahu, Surajit; Ray, Koushik; Yogendra Kumar, M S; Gupta, Shilpa; Kauser, Hina; Kumar, Sanjeev; Mishra, Kshipra; Panjwani, Usha

2012-07-15

The present study was performed to investigate the effects of Valeriana wallichi (VW) aqueous root extract on sleep-wake profile and level of brain monoamines on Sprague-Dawley rats. Electrodes and transmitters were implanted to record EEG and EMG in freely moving condition and the changes were recorded telemetrically after oral administration of VW in the doses of 100, 200 and 300 mg/kg body weight. Sleep latency was decreased and duration of non-rapid eye movement (NREM) sleep was increased in a dose dependent manner. A significant decrease of sleep latency and duration of wakefulness were observed with VW at doses of 200 and 300 mg/kg. Duration of NREM sleep as well as duration of total sleep was increased significantly after treatment with VW at the doses of 200 and 300 mg/kg. VW also increased EEG slow wave activity during NREM sleep at the doses of 200 and 300 mg/kg. Level of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT) and hydroxy indole acetic acid (HIAA) were measured in frontal cortex and brain stem after VW treatment at the dose of 200mg/kg. NE and 5HT level were decreased significantly in both frontal cortex and brain stem. DA and HIAA level significantly decreased only in cortex. DOPAC level was not changed in any brain region studied. In conclusion it can be said that VW water extract has a sleep quality improving effect which may be dependent upon levels of monoamines in cortex and brainstem. Copyright © 2012 Elsevier GmbH. All rights reserved.

A Phase I Study of Triapine® in Combination with Doxorubicin in Patients with Advanced Solid Tumors

PubMed Central

Schelman, William R.; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M.; Ivy, Percy; Wilding, George; Traynor, Anne M.

2011-01-01

Purpose To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine® administered in combination with doxorubicin. Study Design Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine® IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m2 and Triapine® 25 mg/m2. PK analysis was performed at various time-points before and after treatment. Results Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m2, Triapine® 45 mg/m2), 2 patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional 3 patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m2) with Triapine® 45 mg/m2. The 2 patients enrolled on this level had 2 DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine® were reduced to 45 mg/m2 and 25 mg/m2, respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Conclusions Pretreated patients with advanced malignancies can tolerate the combination of Triapine® and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m2 on day 1 and Triapine® 25 mg/m2 on days 1-4 of a 21 day cycle. PMID:19082825

A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors.

PubMed

Schelman, William R; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M; Ivy, Percy; Wilding, George; Traynor, Anne M

2009-05-01

To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine administered in combination with doxorubicin. Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine 25 mg/m(2). PK analysis was performed at various time-points before and after treatment. Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Pretreated patients with advanced malignancies can tolerate the combination of Triapine and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine 25 mg/m(2) on days 1-4 of a 21-day cycle.

Dose-response relationship between urinary polycyclic aromatic hydrocarbons metabolites and urinary 8-hydroxy-2'-deoxyguanosine in a Chinese general population.

PubMed

Sun, Huizhen; Hou, Jian; Zhou, Yun; Yang, Yuqing; Cheng, Juan; Xu, Tian; Xiao, Lili; Chen, Weihong; Yuan, Jing

2017-05-01

Association of exposure to polycyclic aromatic hydrocarbons (PAHs) with increased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation has been reported in occupational population and children. However, studies on the association between them in general population are limited. A total of 1864 eligible subjects from the baseline Wuhan participants of the Wuhan-Zhuhai Cohort Study (n = 3053) were included in this study, after excluding individuals with certain disease and missing data on urinary monohydroxy PAHs (OH-PAHs) and 8-OHdG levels. Urinary monohydroxy PAHs and 8-OHdG levels were measured by gas chromatography-mass spectrometry and high performance liquid chromatography-electrochemical detection, respectively. Association of urinary OH-PAHs with urinary 8-OHdG was analyzed by multiple linear regression analysis. We found a dose-dependent relationship between urinary PAHs metabolites and urinary 8-OHdG (p < 0.05 for all). Furthermore, more evidence for the association of total concentrations of urinary OH-PAHs with 8-OHdG levels were observed in individuals with normal body mass index or central obesity (p < 0.01 for all). There was a dose-dependent relationship between urinary OH-PAHs levels and urinary 8-OHdG levels among a general Chinese population. Exposure to background PAHs may have a greater influence on urinary 8-OHdG levels in individuals with central obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.

PubMed

Hu, Wei; Wang, Wei; Yang, Peinong; Zhou, Chao; Yang, Weifang; Wu, Bo; Lu, Hongsheng; Yang, Haihua

2015-01-01

Epidermal growth factor receptor (EGFR) is a new target for nasopharyngeal carcinoma (NPC) therapy. This prospective phase I study sought to determine the safety and recommended phase II dose of icotinib, a novel highly selective oral EGFR tyrosine kinase inhibitor, in combination with intensity-modulated radiotherapy (IMRT) in patients with NPC. Eligible patients with NPC received escalating doses of icotinib during IMRT. We treated six patients at a particular dose level until the maximum tolerated dose (MTD) was determined. The starting dose was 125 mg, once-daily and the dose was escalated to another level 125 mg, twice- and thrice- daily, until dose-limiting toxicity (DLT) occurred in two or more patients at a dose level. Expression and mutation analysis of EGFR were performed in all cases. A total of twelve patients were enrolled. Three patients experienced DLT (250 mg/day cohort) and MTD was 125 mg/day. Mucositis toxicity appears to be the major DLT. While EGFR expression in tumor tissue was detected in 75% (9/12) patients, EGFR mutation was detected in 16.67% (1/6) patients in 125 mg/day cohort, and 50% (3/6) in 250 mg/day cohort. The combination of icotinib (125 mg/day) and IMRT in patients with locally NPC had an acceptable safety profile and was well tolerated.

Association Between Media Dose, Ad Tagging, and Changes in Web Traffic for a National Tobacco Education Campaign: A Market-Level Longitudinal Study.

PubMed

Shafer, Paul R; Davis, Kevin C; Patel, Deesha; Rodes, Robert; Beistle, Diane

2016-02-17

In 2012, the US Centers for Disease Control and Prevention (CDC) launched Tips From Former Smokers (Tips), the first federally funded national tobacco education campaign. In 2013, a follow-up Tips campaign aired on national cable television networks, radio, and other channels, with supporting digital advertising to drive traffic to the Tips campaign website. The objective of this study was to use geographic and temporal variability in 2013 Tips campaign television media doses and ad tagging to evaluate changes in traffic to the campaign website in response to specific doses of campaign media. Linear regression models were used to estimate the dose-response relationship between weekly market-level television gross rating points (GRPs) and weekly Web traffic to the Tips campaign website. This relationship was measured using unique visitors, total visits, and page views as outcomes. Ad GRP effects were estimated separately for ads tagged with the Tips campaign website URL and 1-800-QUIT-NOW. In the average media market, an increase of 100 television GRPs per week for ads tagged with the Tips campaign website URL was associated with an increase of 650 unique visitors (P<.001), 769 total visits (P<.001), and 1255 total page views (P<.001) per week. The associations between GRPs for ads tagged with 1-800-QUIT-NOW and each Web traffic measure were also statistically significant (P<.001), but smaller in magnitude. Based on these findings, we estimate that the 16-week 2013 Tips television campaign generated approximately 660,000 unique visitors, 900,000 total visits, and 1,390,000 page views for the Tips campaign website. These findings can help campaign planners forecast the likely impact of targeted advertising efforts on consumers' use of campaign-specific websites.

Evaluation of the Hepato and Nephron-Protective Effect of a Polyherbal Mixture using Wistar Albino Rats

PubMed Central

Adebesin, Olumide Adedapo; Okpuzor, Joy

2014-01-01

Aim: A polyherbal formulation prepared from a mixture of leaves of Gongronema latifolia, Ocimum gratissimum and Vernonia amygdalina (GOV) was evaluated for hepato-nephro protective properties against acetaminophen-induced toxicity in Wistar albino rats. Materials and Methods: Normal Wistar albino rats were orally treated with different doses of GOV extract (2, 4 and 8 g/kg b. wt), distilled water and some standard hepatoprotective drugs such as Liv 52 and silymarin for 14 days. However, a day prior to the 14th day, 3 g/kg body weight dose of Acetaminophen (APAP) was administered p.o. 1h before GOV and the standard drugs to induce hepatic and renal damage. The normal control was setup which received only distilled water. The serum levels of liver marker enzymes, biochemical analytes, antioxidant enzymes and hematological parameters were monitored. Results: The results showed that pretreatment of experimental animals with a different doses of the polyherbal formulation dose dependently caused a significant (p≤0.05) increase in the levels of most of the measured hematological parameters but significantly (p≤0.05) reduced the levels of MCV and monocytes when compared to the APAP induced toxin control group. Rats pretreated with GOV exhibited significant (p < 0.05) increase in serum levels of ALP, ALT, AST, GGT, LDH, Cholesterol, Triglycerides, Urea and a subsequent decrease in Albumin, Creatine and Total protein when compared to the normal rats. This trend in enzyme and biochemical analytes levels were significantly (p < 0.05) reversed when compared to toxin control group. GOV significantly (p < 0.05) and dose dependently increased the serum, kidney and hepatic CAT, GPx, GSH, GST, SOD and total protein activity in APAP induced damage in rats compared to the toxin control groups. Conclusion: The data from this study suggest that the polyherbal formulation possess hepato and nephron-protective potential against acetaminophen induced hepatotoxicity in rats, thus providing scientific rationale for its use in traditional medicine for the treatment of liver diseases. PMID:25121002

Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients: Primary Results from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

PubMed Central

Bostom, Andrew G.; Carpenter, Myra A.; Kusek, John W.; Levey, Andrew S.; Hunsicker, Lawrence; Pfeffer, Marc A.; Selhub, Jacob; Jacques, Paul F.; Cole, Edward; Gravens-Mueller, Lisa; House, Andrew A.; Kew, Clifton; McKenney, Joyce L.; Pacheco-Silva, Alvaro; Pesavento, Todd; Pirsch, John; Smith, Stephen; Solomon, Scott; Weir, Matthew

2015-01-01

Background Kidney transplant recipients, like other patients with chronic kidney disease (CKD), experience excess risk of cardiovascular disease (CVD) and elevated total homocysteine (tHcy) concentrations. Observational studies of patients with CKD suggest increased homocysteine is a risk factor for CVD. The impact of lowering total homocysteine (tHcy) levels in kidney transplant recipients is unknown. Methods and Results In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing tHcy concentrations reduced the rate of the primary composite arteriosclerotic CVD outcome (myocardial infarction, stroke, CVD death, resuscitated sudden death, coronary artery or renal artery revascularization, lower extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n= 547 total events; hazards ratio [95% confidence interval] = 0.99 [0.84–1.17]), or secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86–1.26]) or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93–1.43]) compared to the low dose multivitamin. Conclusions Treatment with a high dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. PMID:21482964

Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2-hydroxyethyl methacrylate) Hydrogels.

PubMed

Schver, Giovanna C R M; Lee, Ping I

2018-05-07

Under nonsink dissolution conditions, the kinetic-solubility profiles of amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so-called "spring-and-parachute" concentration-time behaviors. However, the kinetic-solubility profiles of ASDs based on insoluble carriers (including hydrogels) are known to show sustained supersaturation during nonsink dissolution through a matrix-regulated diffusion mechanism by which the supersaturation of the drug is built up gradually and sustained over an extended period without any dissolved polymers acting as crystallization inhibitors. Despite previous findings demonstrating the interplay between supersaturation rates and total doses on the kinetic-solubility profiles of soluble amorphous systems (including ASDs based on dissolution-regulated releases from soluble polymer carriers), the combined effects of supersaturation rates and doses on the kinetic-solubility profiles of ASDs based on diffusion-regulated releases from water-insoluble carriers have not been investigated previously. Thus, the objective of this study is to examine the impacts of total doses and supersaturation-generation rates on the resulting kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We employed a previously established ASD-carrier system based on water-insoluble-cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the weakly basic posaconazole (PCZ). Our results show clearly for the first time that by using the smallest-particle-size fraction and a high dose (i.e., above the critical dose), it is indeed possible to significantly shorten the duration of sustained supersaturation in the kinetic-solubility profile of an ASD based on a water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute dissolution profiles normally associated with ASDs based on soluble carriers. This generates sufficiently rapid initial supersaturation buildup above the critical supersaturation, resulting in more rapid precipitation. Above this smallest-particle-size range, the matrix-diffusion-regulated nonlinear rate of drug release gets slower, which results in a more modest rate of supersaturation buildup, leading to a maximum supersaturation below the critical-supersaturation level without appreciable precipitation. The area-under-the-curve (AUC) values of the in vitro kinetic-solubility concentration-time profiles were used to correlate the corresponding trends in dissolution enhancement. There are observed monotonic increases in AUC values with increasing particle sizes for high-dose ASDs based on water-insoluble hydrogel matrixes, as opposed to the previously reported AUC maxima at some intermediate supersaturation rates or doses in soluble amorphous systems, whereas in the case of low-dose ASDs (i.e., below the critical dose levels), crystallization would be negligible, leading to sustained supersaturation with all particle sizes (i.e., eventually reaching the same maximum supersaturation) and the smallest particle size reaching the maximum supersaturation the fastest. As a result, the smallest particle sizes yield the largest AUC values in the case of low-dose ASDs based on water-insoluble hydrogel matrixes. In addition to probing the interplay between the supersaturation-generation rates and total doses in ASDs based on insoluble hydrogel carriers, our results further support the fact that through either increasing the hydrogel-particle size or lowering the total dose to achieve maximum supersaturation still below the critical-supersaturation level, it is possible to avoid drug precipitation so as to maintain sustained supersaturation.

Implementation of a Lateral TBI protocol in a Mexican Cancer Center

NASA Astrophysics Data System (ADS)

Mesa, Francisco; Esquivel, Carlos; Eng, Tony; Papanikolaou, Niko; Sosa, Modesto A.

2008-08-01

The development of a Lateral Total Body Irradiation protocol to be implemented at a High Specialty Medical Unit in Mexico as preparatory regimen for bone marrow transplant and treatment of several lymphomas is presented. This protocol was developed following AAPM specifications and has been validated for application at a cancer care center in United States. This protocol fundamentally focuses on patient care, avoiding instability and discomfort that may be encountered by other treatment regimes. In vivo dose verification with TLD-100 chips for each anatomical region of interest was utilized. TLD-100 chips were calibrated using a 6 MV photon beam for 10-120 cGy. Experimental results show TLD measurements with an error less than 1%. Standard deviations for calculated and measured doses for seven patients have been obtained. Data gathered for different levels of compensation indicate that a 3% measured tolerance level is acceptable. TLD point-dose measurements have been used to verify the dose beyond partial transmission lung blocks. Dose measurements beyond the lung block showed variation about 50% respects to prescribe dose. Midplane doses to the other anatomical sites were less than 2.5% respect of the prescribed dose.

Possible biochemical effects following inhibition of ethanol-induced gastric mucosa damage by Gymnema sylvestre in male Wistar albino rats.

PubMed

Al-Rejaie, Salim S; Abuohashish, Hatem M; Ahmed, Mohammed M; Aleisa, Abdulaziz M; Alkhamees, Osama

2012-12-01

Gymnema sylvestre (GS) R. Br. (Gymnema) (Asclepiadaceae) has been used from ancient times as a folk medicine for the treatment of diabetes, obesity, urinary disorder, and stomach stimulation. The present study was designed to investigate the effects of G. sylvestre leaves ethanol extract on gastric mucosal injury in rats. Gastric mucosal damage was induced by 80% ethanol in 36 h fasted rats. The effect of G. sylvestre on gastric secretions induced in Shay rats was estimated. In stomach, wall mucus, non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), total proteins and nucleic acids levels were estimated. Histopathological changes were observed. G. sylvestre pretreatment at doses of 100, 200 and 400 mg/kg provided 27, 49, and 63% protection against the ulcerogenic effect of ethanol, respectively. Pylorus ligation accumulated 10.24 mL gastric secretions with 66.56 mEq of acidity in control rats. Pretreatment with G. sylvestre significantly inhibited the secretions volume and acidity in dose-dependent manner. Ethanol caused significant depletion in stomach-wall mucus (p < 0.001), total proteins (p < 0.01), nucleic acids (p < 0.001), and NP-SH (p < 0.001) levels. Pretreatment with G. sylvestre showed protection against these depleted levels in dose-dependent manner. The MDA levels increased from 19.02 to 29.22 nmol/g by ethanol ingestion and decreased with G. sylvestre pretreatments in dose-dependent manner. The protective effect of G. sylvestre observed in the present study is attributed to its effect on mucus production, increase in nucleic acid and NP-SH levels, which appears to be mediated through its free radical scavenging ability and/or possible cytoprotective properties.

Safe extensive tumescent liposuction with segmental infiltration of lower concentration lidocaine under monitored anesthesia care.

PubMed

Wang, Gang; Cao, Wei-Gang; Li, Sheng-Li; Liu, Li-Na; Jiang, Zhao-Hua

2015-01-01

Tumescent anesthesia makes it feasible to perform liposuction in an office setting. There are often patients who desire extensive liposuction on approximately 30% of total body surface area, which means the lidocaine total dose might be over the dosing recommendation. So the segmental infiltration is applied, although the concentration of lidocaine in tumescent fluid is gradually reduced to 0.0252%. Moreover, supplemental intravenous (IV) sedation using monitored anesthesia care is usually applied concurrently to help alleviate discomfort and pain of the patients during tumescent anesthetic infusion and fat extraction which in turn increases the risks of potential lidocaine toxicity due to possible drug interactions. This study was to demonstrate the safety of segmental infiltration of tumescent fluid with lower lidocaine concentration combined with IV sedation in extensive liposuction and determine whether the risk of lidocaine toxicity is increased in this protocol. Ten female patients who requested the extensive liposuction participated in the study. The targeted areas were divided into 2 segments and treated in turn in 1 session. Lidocaine (1600 mg) was infiltrated into the first segment, and approximately 928 mg lidocaine was subsequently infiltrated after accomplishment of the first segment operation. Serum levels of lidocaine were taken every 4 hours during the first 24 hours after the second infiltration. The average time of the procedure is 222 (33) minutes. The dose and total amount of lidocaine injected are 40.7 (5.8) mg/kg and 2528.2 (155.2) mg, respectively. The total volume of the infusates and aspirates are 9918.1 (494) and 6325 (1461.6) mL, respectively, the ratio of total infusates to total aspirates is 1.66 (0.45). The total aspirated fat and fluids are 3280 (1051.8) and 3045 (824.1) mL, respectively. The peak lidocaine levels [2.18 (0.63) μg/mL] occurred after 12 to 20 hours [16.4 (2.27) hours]. No significant correlation between dose per kilogram body weight or total dose of lidocaine infiltrated and its peak levels or time existed. The extensive liposuction covering the 30% total body surface areas was well tolerated by the patients under tumescent anesthesia in combination with the supplemental IV sedation. Our previous study on the fluid management has demonstrated the risk of hypovolemia or fluid overload is very low with this technique, although the patients who received only maintenance fluid (500 mL) in the operating room and could discharge and resume oral intake after 6 hours of recovery room stay. The adequate anesthesia support is available in our office-based setting with adequate recovery facilities in place. It has a high margin of safety, without increasing of lidocaine toxicity or adverse cardiopulmonary sequelae while using a segmental tumescent infiltration with lower concentration of lidocaine.

UV controlling factors and trends derived from the ground-based measurements taken at Belsk, Poland, 1976-1994

NASA Astrophysics Data System (ADS)

KrzyśCin, Janusz W.

1996-07-01

Monthly means of UV erythemal dose at ground level from the Robertson-Berger (RB) sunburn meter (1976-1992) and the UV-Biometer model 501 MED meter (1993-1994) located at Belsk (21°E, 52°N), Poland, are examined. The monthly means are calculated from all-sky daily means of UV erythemal dose. Ancillary measurements of column ozone (by Dobson spectrophotometer), sunshine duration (by Campbell-Stokes heliograph), and total (sun and sky) radiation (by a pyranometer) are considered to explain variations in the UV data. A multiple regression model is proposed to study trends in the UV data. The model accounts for the UV erythemal dose changes induced by total ozone, sunshine duration (surrogate for cloud cover variations), or total solar radiation (surrogate for combined cloud cover and atmospheric turbidity impact on the UV radiation), trends due to instrument drift, step changes in the data, and serial correlations. A strong relationship between monthly all-sky UV erythemal dose changes and total ozone (and total solar radiation) is found. Calculations show that an erythemal radiative amplification factor (RAF) due to ozone under all skies is close to its clear-sky value (about 1). However, the model gives evidence that the RAF due to ozone is smaller for cloudier (and/or more turbid) atmospheres than long-term reference. Total solar radiation change of 1% is associated with a change of 0.7% in the UV erythemal dose. Modeled trends in the Belsk's UV data, inferred from the model using ozone and total solar radiation as the UV forcing factors, are 2.3% ± 0.4% (1σ) per decade in the period 1976-1994. The large increase in the UV erythemal dose, of the order of 4% per decade due to ozone depletion (-3.2% per decade), is partially compensated by a decreasing tendency (-2.8% per decade) in total solar radiation. The model estimates the trend in the UV data of the order of 0.1% per decade (not statistically significant) due to superposition of the instrument drift and long-term effects related to other UV influencing factors (not parameterized by the model).

Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

PubMed

Ahmad, Feroz; Tabassum, Nahida

2013-01-01

To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

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

Tada, Takuhito, E-mail: tada@msic.med.osaka-cu.ac.jp; Department of Radiology, Izumi Municipal Hospital, Izumi; Chiba, Yasutaka

2012-05-01

Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m{sup 2}) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m{sup 2}). Total doses were 54 Gy in 36 fractions, 60 Gymore » in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade {>=}4 esophagitis and neutropenic fever and Grade {>=}3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.« less

The susceptibility of TaO x-based memristors to high dose rate ionizing radiation and total ionizing dose

DOE PAGES

McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

2014-11-11

This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaO x) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×10 7 rad(Si)/s to 4.7 ×10 8 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×10 8 rad(Si)/s. This is the first dose rate study on any type ofmore » memristive memory technology. In addition to assessing the tolerance of TaO x memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

Reversal of the toxic effects of cachectin by concurrent insulin administration.

PubMed

Fraker, D L; Merino, M J; Norton, J A

1989-06-01

Rats treated with recombinant human tumor necrosis factor-cachectin, 100 micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in body weight gain vs. saline-treated controls. Concurrent neutral protamine hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of these changes to control levels without causing any treatment deaths. The improvement seen with insulin was dose independent. Five days of cachectin treatment caused a severe interstitial pneumonitis, periportal inflammation in the liver, and an increase in wet organ weight in the heart, lungs, kidney, and spleen. Concurrent insulin treatment led to near total reversal of these histopathologic changes. Cachectin treatment did not significantly change blood glucose levels from control values of 130-140 mg/dl, but insulin plus cachectin caused a significant decrease in blood glucose from 1 through 12 h after injection. Administration of high-dose insulin can near totally reverse the nutritional and histopathologic toxicity of sublethal doses of cachectin in rats.

TH-EF-BRB-11: Volumetric Modulated Arc Therapy for Total Body Irradiation

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

Ouyang, L; Folkerts, M; Hrycushko, B

Purpose: To develop a modern, patient-comfortable total body irradiation (TBI) technique suitable for standard-sized linac vaults. Methods: An indexed rotatable immobilization system (IRIS) was developed to make possible total-body CT imaging and radiation delivery on conventional couches. Treatment consists of multi-isocentric volumetric modulated arc therapy (VMAT) to the upper body and parallel-opposed fields to the lower body. Each isocenter is indexed to the couch and includes a 180° IRIS rotation between the upper and lower body fields. VMAT fields are optimized to satisfy lung dose objectives while achieving a uniform therapeutic dose to the torso. End-to-end tests with a randomore » phantom were used to verify dosimetric characteristics. Treatment plan robustness regarding setup uncertainty was assessed by simulating global and regional isocenter setup shifts on patient data sets. Dosimetric comparisons were made with conventional extended distance, standing TBI (cTBI) plans using a Monte Carlo-based calculation. Treatment efficiency was assessed for eight courses of patient treatment. Results: The IRIS system is level and orthogonal to the scanned CT image plane, with lateral shifts <2mm following rotation. End-to-end tests showed surface doses within ±10% of the prescription dose, field junction doses within ±15% of prescription dose. Plan robustness tests showed <15% changes in dose with global setup errors up to 5mm in each direction. Local 5mm relative setup errors in the chest resulted in < 5% dose changes. Local 5mm shift errors in the pelvic and upper leg junction resulted in <10% dose changes while a 10mm shift error causes dose changes up to 25%. Dosimetric comparison with cTBI showed VMAT-TBI has advantages in preserving chest wall dose with flexibility in leveraging the PTV-body and PTV-lung dose. Conclusion: VMAT-TBI with the IRIS system was shown clinically feasible as a cost-effective approach to TBI for standard-sized linac vaults.« less

Conformity of commercial oral single solid unit dose packages in hospital pharmacy practice.

PubMed

Thibault, Maxime; Prot-Labarthe, Sonia; Bussières, Jean-François; Lebel, Denis

2008-06-01

There are limited published data on the labelling of single unit dose packages in hospitals. The study was conducted in three large hospitals (two adult and one paediatric) in the metropolitan Montreal area, Quebec, Canada. The objective is to evaluate the labelling of commercial oral single solid unit dose packages available in Canadian urban hospital pharmacy practice. The study endpoint was the labelling conformity of each unit dose package for each criterion and overall for each manufacturer. Complete labelling of unit dose packages should include the following information: (1) brand name, (2) international non-proprietary name or generic name, (3) dosage, (4) pharmaceutical form, (5) manufacturer's name, (6) expiry date, (7) batch number and (8) drug identification number. We also evaluated the ease with which a single unit dose package is detached from a multiple unit dose package for quick, easy and safe use by pharmacy staff. Conformity levels were compared between brand-name and generic packages. A total of 124 different unit dose packages were evaluated. The level of conformity of each criterion varied between 19 and 50%. Only 43% of unit dose packages provided an easy-to-detach system for single doses. Among the 14 manufacturers with three or more unit dose packages evaluated, eight (57%) had a conformity level less than 50%. This study describes the conformity of commercial oral single solid unit dose packages in hospital pharmacy practice in Quebec. A large proportion of unit dose packages do not conform to a set of nine criteria set out in the guidelines of the American Society of Health-System Pharmacists and the Canadian Society of Hospital Pharmacists.

A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

2002-03-01

To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being

Dose Assessment of Los Alamos National Laboratory-Derived Residual Radionuclides in Soils within Tract A-18-2 for Land Conveyance and Transfer Decisions

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

Ruedig, Elizabeth; Whicker, Jeffrey Jay

In 2017, soil sampling for radiological materials was conducted within Tract A-18-2 at Los Alamos National Laboratory (LANL) for land conveyance decisions. Measurements of radionuclides in soil samples were evaluated against a recreational use scenario, and all measurements were below screening action levels for each radionuclide. The total estimated dose was less than 1 mrem/yr (<10 μSv/yr) for a hypothetical recreational user (compared with a dose limit of 25 mrem/yr [250 μSv/yr]). Dose estimates were based on the 95% upper confidence levels for radionuclide concentrations within the Tract. Dose estimates less than 3 mrem/yr are considered to be as lowmore » as reasonably achievable (ALARA), therefore no follow-up analysis was conducted. Release of this property is consistent with the requirements of DOE Order 458.1 (DOE 2013) and Policy 412 (LANL 2014).« less

Effects of ursolic acid on glucose metabolism, the polyol pathway and dyslipidemia in non-obese type 2 diabetic mice.

PubMed

Lee, Jin; Lee, Hae-In; Seo, Kown-Il; Cho, Hyun Wook; Kim, Myung-Joo; Park, Eun-Mi; Lee, Mi-Kyung

2014-07-01

Ursolic acid (UA) is a pentacyclic triterpenoid compound that naturally occurs in fruits, leaves and flowers of medicinal herbs. This study investigated the dose-response efficacy of UA (0.01 and 0.05%) on glucose metabolism, the polyol pathway and dyslipidemia in streptozotocin/nicotinamide-induced diabetic mice. Supplement with both UA doses reduced fasting blood glucose and plasma triglyceride levels in non-obese type 2 diabetic mice. High-dose UA significantly lowered plasma free fatty acid, total cholesterol and VLDL-cholesterol levels compared with the diabetic control mice, while LDL-cholesterol levels were reduced with both doses. UA supplement effectively decreased hepatic glucose-6-phosphatase activity and increased glucokinase activity, the glucokinase/glucose-6-phosphatase ratio, GLUT2 mRNA levels and glycogen content compared with the diabetic control mice. UA supplement attenuated hyperglycemia-induced renal hypertrophy and histological changes. Renal aldose reductase activity was higher, whereas sorbitol dehydrogenase activity was lower in the diabetic control group than in the non-diabetic group. However, UA supplement reversed the biochemical changes in polyol pathway to normal values. These results demonstrated that low-dose UA had preventive potency for diabetic renal complications, which could be mediated by changes in hepatic glucose metabolism and the renal polyol pathway. High-dose UA was more effective anti-dyslipidemia therapy in non-obese type 2 diabetic mice.

Site-specific range uncertainties caused by dose calculation algorithms for proton therapy

NASA Astrophysics Data System (ADS)

Schuemann, J.; Dowdell, S.; Grassberger, C.; Min, C. H.; Paganetti, H.

2014-08-01

The purpose of this study was to assess the possibility of introducing site-specific range margins to replace current generic margins in proton therapy. Further, the goal was to study the potential of reducing margins with current analytical dose calculations methods. For this purpose we investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict the range of proton fields. Dose distributions predicted by an analytical pencil-beam algorithm were compared with those obtained using Monte Carlo (MC) simulations (TOPAS). A total of 508 passively scattered treatment fields were analyzed for seven disease sites (liver, prostate, breast, medulloblastoma-spine, medulloblastoma-whole brain, lung and head and neck). Voxel-by-voxel comparisons were performed on two-dimensional distal dose surfaces calculated by pencil-beam and MC algorithms to obtain the average range differences and root mean square deviation for each field for the distal position of the 90% dose level (R90) and the 50% dose level (R50). The average dose degradation of the distal falloff region, defined as the distance between the distal position of the 80% and 20% dose levels (R80-R20), was also analyzed. All ranges were calculated in water-equivalent distances. Considering total range uncertainties and uncertainties from dose calculation alone, we were able to deduce site-specific estimations. For liver, prostate and whole brain fields our results demonstrate that a reduction of currently used uncertainty margins is feasible even without introducing MC dose calculations. We recommend range margins of 2.8% + 1.2 mm for liver and prostate treatments and 3.1% + 1.2 mm for whole brain treatments, respectively. On the other hand, current margins seem to be insufficient for some breast, lung and head and neck patients, at least if used generically. If no case specific adjustments are applied, a generic margin of 6.3% + 1.2 mm would be needed for breast, lung and head and neck treatments. We conclude that the currently used generic range uncertainty margins in proton therapy should be redefined site specific and that complex geometries may require a field specific adjustment. Routine verifications of treatment plans using MC simulations are recommended for patients with heterogeneous geometries.

Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease.

PubMed

Lenz, Robert A; Pritchett, Yili L; Berry, Scott M; Llano, Daniel A; Han, Shu; Berry, Donald A; Sadowsky, Carl H; Abi-Saab, Walid M; Saltarelli, Mario D

2015-01-01

ABT-089, an α4β2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian response-adaptive randomization algorithm dynamically assigned allocation probabilities based on interim ADAS-Cog total scores. A normal dynamic linear model for dose-response relationships and a longitudinal model for predicting final ADAS-cog score were employed in the algorithm. Stopping criteria for futility or success were defined. The futility stopping criterion was met, terminating the study with 337 patients randomized. No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all dose levels. When administered as adjunctive therapy to acetylcholinesterase inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease. The adaptive study design enabled the examination of a broad dose range, enabled rapid determination of futility, and reduced patient exposure to nonefficacious doses of the investigational compound.

Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

2002-01-01

Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

Effects of medetomidine on serum glucose in cattle calves.

PubMed

Tariq, Muhammad; Kalhoro, Amir Bukhsh; Sarwar, Mian Saeed; Khan, Hamayun; Ahmad, Shakoor; Hassan, Sayed Mubashir; Zahoor, Arshad

2016-05-01

An experimental study was carried out to compare physiological effects (serum glucose level) of medetomidine in Red Sindhi cattle calves at three different doses i.e. 8, 10 and 12µg/kg body weight intravenously. Medetomidine produced a dose dependent significant (P<0.01) increase in serum glucose level with a maximum increase observed at 30 minutes with 8µg/kg, 10μg/kg and 12μg/kg body weight respectively. Start of sedation, degree of sedation and total duration of sedation were all dose dependent and the values obtained were significantly (P<0.01) different from each other. It was observed that the sedation was rapid, deep and longer with the higher doses of medetomidine i.e. 12μg/kg. The results of the present study shows that medetomidine is a very effective and safest drug use as sedative for calves which in lower doses (8μg/kg) can be used as a pre-anesthetic and for restraining of the animal, while higher calculated doses (10μg/kg, 12μg/kg) can be used to execute the minor surgical procedures.

Impact of Long-Term Serum Platinum Concentrations on Neuro- and Ototoxicity in Cisplatin-Treated Survivors of Testicular Cancer

PubMed Central

Sprauten, Mette; Darrah, Thomas H.; Peterson, Derick R.; Campbell, M. Ellen; Hannigan, Robyn E.; Cvancarova, Milada; Beard, Clair; Haugnes, Hege S.; Fosså, Sophie D.; Oldenburg, Jan; Travis, Lois B.

2012-01-01

Purpose Cisplatin-induced neurotoxicity and ototoxicity (NTX) are important adverse effects after chemotherapy for testicular cancer (TC). Although serum platinum is measurable years after therapy, its impact on NTX has not been evaluated. Patients and Methods In all, 169 cisplatin-treated survivors of TC provided blood samples at Survey I and reported NTX during Survey I (1998-2002) and Survey II (2007-2008). Serum platinum was quantified by inductively coupled plasma mass spectrometry. Patient-reported outcomes were evaluated with the Scale for Chemotherapy-Induced Neurotoxicity (SCIN), regarding the extent of symptom bother as 0, “not at all”; 1, “a little”; 2, “quite a bit”; or 3, “very much.” Summing the six symptom scores yielded a total SCIN score of 0 to 18. Categorizing total SCIN scores into quartiles yielded similar-sized groups with increasing symptoms. Multivariate ordinal logistic regression analyses evaluated associations between NTX and long-term serum platinum levels, adjusting for cisplatin dose, dosing schedule, and age. Results At Survey I, a significant four- to five-fold association with total SCIN score emerged for the highest serum platinum quartile (odds ratio [OR], 4.69; 95% CI, 1.82 to 12.08). Paresthesias and Raynaud's syndrome (hands and feet) showed significant two- to four-fold increased risks with the highest platinum quartile. At Survey II, total SCIN score remained significantly associated with the highest platinum quartile (OR, 4.28; 95% CI, 1.36 to 13.48). Paresthesias (hands and feet) and tinnitus showed significant three- to four-fold increased risks for the highest platinum quartile. Cumulative cisplatin dose was not associated with total SCIN score or individual SCIN symptoms in multivariate analyses. Conclusion Here we document a significant relationship between increasing levels of residual serum platinum and NTX severity after adjusting for initial cisplatin dose. PMID:22184390

24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain: implications for caffeine-induced depression.

PubMed

Haleem, D J; Yasmeen, A; Haleem, M A; Zafar, A

1995-01-01

Caffeine injected at doses of 20, 40 and 80 mg/kg increased brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in rat brain. In view of a possible role of 5-HT in caffeine-induced depression the effects of repeated administration of high doses of caffeine on brain 5-HT metabolism are investigated in rats. Caffeine was injected at doses of 80 mg/kg daily for five days. Control animals were injected with saline daily for five days. On the 6th day caffeine (80 mg/kg) injected to 5 day saline injected rats increased brain levels of tryptophan, 5-HT and 5-HIAA. Plasma total tryptophan levels were not affected and free tryptophan increased. Brain levels of 5-HT and 5-HIAA but not tryptophan decreased in 5 day caffeine injected rats injected with saline on the 6th day. Plasma total and free tryptophan were not altered in these rats. Caffeine-induced increases of brain tryptophan but not 5-HT and 5-HIAA were greater in 5 day caffeine than 5 day saline injected rats. The findings are discussed as repeated caffeine administration producing adaptive changes in the serotonergic neurons to decrease the conversion of tryptophan to 5-HT and this may precipitate depression particularly in conditions of caffeine withdrawal.

Clinical distinctions of radiation sickness with exposure of different parts of the human body to radiation

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

Nevskaya, G.F.; Abramova, G.M.; Volkova, M.A.

1982-01-12

The clinical picture of radiation sickness of 139 radiological patients exposed to local irradition of the head, chest, and stomach with efficient doses of 210 rad was examined. It was found that at fractionated local irraditions the clinical symptom-complex of radiation sickness was identifical to that seen as a result of total-body irradiation. During head irradiation the major symptom was headache and during stomach irradiation nausea. The severity level of radiation damage measured with respect to the clinical symptom-complex as a whole with the aid of the bioinformation model was similar during irradiations of the head and stomach, much highermore » during irradiation of the chest. During head and stomach irradiations the severity level of radiation damage was proportional to the efficient dose. During chest irradiation there was no correlation between the severity level and the exposure to doses of 210 rad.« less

The risk of solar proton events to space missions

NASA Technical Reports Server (NTRS)

Burrell, M. O.

1972-01-01

The total dose in rads-tissue from solar protons was tabulated for weekly time intervals, and the number of weeks which gave a dose above 25 rads behind 10 g/sq cm of aluminum for the active 6 years of the 19th cycle were called dangerous or large event weeks. The number of such event weeks was found to be only 3 weeks for the past 20 years. Even though the chance for smaller events is examined, it was found that for any reasonable, high confidence level (95%), the smaller events could be ignored. Consequently, the total particle flux for the 19th cycle was divided by a factor of 3 and determined a single large event week. Using this spectrum, the tissue dose in rads is calculated at the center of an aluminum spherical shell.

The contribution of interventional cardiology procedures to the population radiation dose in a ‘health-care level I’ representative region

PubMed Central

Peruzzo Cornetto, Andrea; Aimonetto, Stefania; Pisano, Francesco; Giudice, Marcello; Sicuro, Marco; Meloni, Teodoro; Tofani, Santi

2016-01-01

This study evaluates per-procedure, collective and per capita effective dose to the population by interventional cardiology (IC) procedures performed during 2002–11 at the main hospital of Aosta Valley Region that can be considered as representative of the health-care level I countries, as defined by the UNSCEAR, based on its socio-demographic characteristics. IC procedures investigated were often multiple procedures in patients older than 60 y. The median extreme dose-area product values of 300 and 22 908 cGycm2 were found for standard pacemaker implantation and coronary angioplasty, respectively, while the relative mean per-procedure effective dose ranged from 0.7 to 47 mSv. A 3-fold increase in frequency has been observed together with a correlated increase in the delivered per capita dose (0.05–0.27 mSv y−1) and the collective dose (5.8–35 man Sv y−1). Doses increased particularly from 2008 onwards mainly because of the introduction of coronary angioplasty procedures in the authors’ institution. IC practice contributed remarkably in terms of effective dose to the population, delivering ∼10 % of the total dose by medical ionising radiation examination categories. PMID:26012484

Outreach hepatitis B vaccination of female sex workers in central-west Brazil: immunization status, compliance, and immune response.

PubMed

Carneiro, Luciene Moraes; Mousquer, Gina Jonasson; Pinheiro, Raquel Silva; Castro, Ana Rita Coimbra Motta; França, Divânia Dias Da Silva; Caetano, Karlla Antonieta Amorim; Carneiro, Megmar Aparecida dos Santos; Martins, Regina Maria Bringel; Matos, Marcos André de; Castro, Lisie; Rezende, Grazielli; Teles, Sheila Araujo

2014-01-01

To evaluate the hepatitis B immunization status of female sex workers (FSWs) in Central-West Brazil and to evaluate their compliance with and immune response to hepatitis B vaccination delivered using outreach strategies. A total of 721 FSWs recruited in 2 large cities in Central-West Brazil were interviewed and screened for the presence of hepatitis B virus (HBV) markers. Hepatitis B vaccine was offered to all women susceptible to HBV, using outreach strategies. The immune response of FSWs who received a full course of vaccine was assessed following the final vaccine dose. We found that 27.6% of FSWs, the majority of whom were aged 18 to 25 years, had serological evidence of previous hepatitis B vaccination. A total of 434 FSWs were eligible for vaccination, 389 (89.6%) of whom accepted the first hepatitis B vaccine dose. Of those, 64% received a second dose and 37.5% received all three doses. Through the outreach strategy, there was a 52.2% increase in the number of women who received the second dose and a 67% increase in the number who received the third dose. Of the 146 women who received a full course of vaccine, 105 accepted testing for quantitative anti-HBs (hepatitis B surface antibody) following the final vaccine dose, and 92.4% of those tested had developed protective levels of anti-HBs. Lower education level, workplace, and length of prostitution were predictors of full-vaccine acceptance. The present findings illustrate the benefits of using outreach strategies to overcome the difficulties of vaccinating hard-to-reach populations such as FSWs.

High-speed large angle mammography tomosynthesis system

NASA Astrophysics Data System (ADS)

Eberhard, Jeffrey W.; Staudinger, Paul; Smolenski, Joe; Ding, Jason; Schmitz, Andrea; McCoy, Julie; Rumsey, Michael; Al-Khalidy, Abdulrahman; Ross, William; Landberg, Cynthia E.; Claus, Bernhard E. H.; Carson, Paul; Goodsitt, Mitchell; Chan, Heang-Ping; Roubidoux, Marilyn; Thomas, Jerry A.; Osland, Jacqueline

2006-03-01

A new mammography tomosynthesis prototype system that acquires 21 projection images over a 60 degree angular range in approximately 8 seconds has been developed and characterized. Fast imaging sequences are facilitated by a high power tube and generator for faster delivery of the x-ray exposure and a high speed detector read-out. An enhanced a-Si/CsI flat panel digital detector provides greater DQE at low exposure, enabling tomo image sequence acquisitions at total patient dose levels between 150% and 200% of the dose of a standard mammographic view. For clinical scenarios where a single MLO tomographic acquisition per breast may replace the standard CC and MLO views, total tomosynthesis breast dose is comparable to or below the dose in standard mammography. The system supports co-registered acquisition of x-ray tomosynthesis and 3-D ultrasound data sets by incorporating an ultrasound transducer scanning system that flips into position above the compression paddle for the ultrasound exam. Initial images acquired with the system are presented.

Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma

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

Merchant, Thomas E.; Kiehna, Erin N.; Li Chenghong

2006-05-01

Purpose: Model the effects of radiation dosimetry on IQ among pediatric patients with central nervous system (CNS) tumors. Methods and Materials: Pediatric patients with CNS embryonal tumors (n = 39) were prospectively evaluated with serial cognitive testing, before and after treatment with postoperative, risk-adapted craniospinal irradiation (CSI) and conformal primary-site irradiation, followed by chemotherapy. Differential dose-volume data for 5 brain volumes (total brain, supratentorial brain, infratentorial brain, and left and right temporal lobes) were correlated with IQ after surgery and at follow-up by use of linear regression. Results: When the dose distribution was partitioned into 2 levels, both had amore » significantly negative effect on longitudinal IQ across all 5 brain volumes. When the dose distribution was partitioned into 3 levels (low, medium, and high), exposure to the supratentorial brain appeared to have the most significant impact. For most models, each Gy of exposure had a similar effect on IQ decline, regardless of dose level. Conclusions: Our results suggest that radiation dosimetry data from 5 brain volumes can be used to predict decline in longitudinal IQ. Despite measures to reduce radiation dose and treatment volume, the volume that receives the highest dose continues to have the greatest effect, which supports current volume-reduction efforts.« less

Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer.

PubMed

Fidias, Panos; Pennell, Nathan A; Boral, Anthony L; Shapiro, Geoffrey I; Skarin, Arthur T; Eder, Joseph P; Kwoh, T Jesse; Geary, Richard S; Johnson, Bruce E; Lynch, Thomas J; Supko, Jeffrey G

2009-09-01

A phase I trial was performed to evaluate the administration of carboplatin/paclitaxel in combination with ISIS-5132, a phosphorothioate antisense oligodeoxynucleotide inhibitor of c-raf-1 kinase expression, in patients with advanced non-small cell lung cancer (NSCLC). Previously untreated patients with stage IIIB/IV NSCLC received ISIS 5132 by continuous intravenous infusion at 2.0 mg/kg/d for 14 days. Starting doses were paclitaxel 175 mg/m(2) and carboplatin targeting an area under the free platinum plasma concentration-time curve (AUC(fp)) of 5 mg . min/ml (dose level 1). The carboplatin dose was then increased to AUC(fp) 6 mg . min/ml (dose level 2) after which the paclitaxel dose was increased to 200 mg/m(2) (dose level 3). The maximum tolerated dose was established by toxicity during the first two 21-day cycles of therapy. The pharmacokinetics of all three agents was determined before and during the ISIS 5132 infusion. Thirteen patients were treated with the carboplatin/paclitaxel/ISIS 5132 combination. Dose-limiting neutropenia occurred in two patients at dose level 3. Grade 3 and 4 nonhematologic toxicities were infrequent and limited to nausea and constipation. The maximum tolerated doses were carboplatin AUC(fp) 6 mg . min/ml, paclitaxel 175 mg/m(2), and ISIS 5132 2.0 mg/kg/d for 14 days. There were no objective responses and the concurrent infusion of ISIS 5132 did not alter the plasma pharmacokinetics of paclitaxel or total platinum. ISIS 5132 can be safely combined with standard doses of carboplatin and paclitaxel. Combining cytotoxic chemotherapeutic agents with inhibitors of aberrant signal transduction mediated by Raf proteins produced no objective responses in the dose and schedule administered in this study.

Space Radiation Effects and Reliability Consideration for the Proposed Jupiter Europa Orbiter

NASA Technical Reports Server (NTRS)

Johnston, Allan

2011-01-01

The proposed Jupiter Europa Orbiter (JEO) mission to explore the Jovian moon Europa poses a number of challenges. The spacecraft must operate for about seven years during the transit time to the vicinity of Jupiter, and then endure unusually high radiation levels during exploration and orbiting phases. The ability to withstand usually high total dose levels is critical for the mission, along with meeting the high reliability standards for flagship NASA missions. Reliability of new microelectronic components must be sufficiently understood to meet overall mission requirements.The proposed Jupiter Europa Orbiter (JEO) mission to explore the Jovian moon Europa poses a number of challenges. The spacecraft must operate for about seven years during the transit time to the vicinity of Jupiter, and then endure unusually high radiation levels during exploration and orbiting phases. The ability to withstand usually high total dose levels is critical for the mission, along with meeting the high reliability standards for flagship NASA missions. Reliability of new microelectronic components must be sufficiently understood to meet overall mission requirements.

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

[Pharmacokinetics and clinical studies of flomoxef in the pediatric field].

PubMed

Motohiro, T; Oda, K; Aramaki, M; Kawakami, A; Tanaka, K; Koga, T; Shimada, Y; Tomita, S; Sakata, Y; Fujimoto, T

1987-08-01

Flomoxef (FMOX, 6315-S), a new intravenous cephem antibiotics, was administered to a total of 11 cases with their ages ranging from 7 years and 4 months to 10 years and 10 months. Among them, two were administered with (FMOX at) a dose level of 10 mg/kg, three each with 20 mg/kg and 40 mg/kg using one shot intravenous injection, and the remaining 3 with 40 mg/kg by intravenous drip infusion over 30 minutes. Plasma concentrations, urine concentrations and urinary recovery rates were determined. The clinical efficacy of FMOX was evaluated in 2 cases with tonsillitis, 45 with acute pneumonia, 10 with urinary tract infections, 2 with purulent lymphadenitis, and 2 with abscess, a total of 61 cases. Of these cases, one case of pneumonia in which a side effect occurred was excluded from the evaluation because the treatment was interrupted short of the required period. In the remaining 60 cases, the mean daily dose was 79.3 mg/kg in 3 or 4 divided doses and, except one case treated by 30-minute intravenous drip infusion, all cases were treated by one shot intravenous injection for a mean period of 6 days. Bacteriological effects of FMOX, its side effects and influences on laboratory test values were also investigated. 1. Maximum plasma concentrations after one shot intravenous injections of FMOX occurred at 5 minutes after administration regardless of dose levels (10 mg/kg in 2 cases, 20 mg/kg in 3 and 40 mg/kg in 3). Mean peak values obtained upon the 3 different dose levels were 62.5, 103.1 and 244.7 micrograms/ml, respectively. Mean plasma half-lives were 0.670, 0.915 and 0.595 hour, and mean AUCs were 33.0, 65.2 and 133.1 micrograms.hr/ml, respectively. Thus, a positive dose-response relationship was found among the 3 doses. 2. Plasma concentrations after 30-minute intravenous drip infusions of FMOX at 40 mg/kg always reached a peak at 30 minutes after the initiation of infusion, i.e. at the completion of infusion, and the mean value for 3 administrations was 151.0 micrograms/ml. The mean half-life was 0.973 hour and the mean AUC was 149.1 micrograms.hr/ml. 3. Maximum concentrations in urine after one shot intravenous injections of FMOX were always obtained in 0 approximately 2 hours after administration regardless of dose levels (10 mg/kg, 2 cases, 20 mg/kg, 3 cases and at 40 mg/kg, 3 cases) and mean values for the 3 dose levels were 2,570, 4,410 and 6,290 micrograms/ml, respectively. Thus, urine concentrations were also dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes.

PubMed

Heise, T; Nosek, L; Bøttcher, S G; Hastrup, H; Haahr, H

2012-10-01

Insulin degludec (IDeg) is a new-generation, ultra-long-acting basal insulin that forms soluble multihexamers upon subcutaneous injection, resulting in a depot from which IDeg is absorbed slowly and continuously into circulation. This double-blind, two-period, incomplete block cross-over trial investigated the pharmacodynamic and pharmacokinetic properties of IDeg at steady state (SS) in people with type 2 diabetes. Forty-nine subjects treated with insulin without concomitant oral anti-diabetic drugs were given IDeg (0.4, 0.6 and/or 0.8 U/kg) once daily for two 6-day periods, separated by an interval of 13-21 days. Following dosing on Day 6, subjects underwent a 26-h euglycaemic glucose clamp (Biostator®; clamp blood glucose level: 90 mg/dl; 5.0 mmol/l). Pharmacokinetic samples were taken until 120 h after last dosing. For all dose levels, the mean glucose infusion rate (GIR) profiles were flat and stable. The glucose-lowering effect of IDeg was evenly distributed over the dosing interval τ, with area under the curve (AUC) for each of the four 6-h intervals being approximately 25% of the total AUC (AUC(GIR) (,τ,) (SS) ). Total glucose-lowering effect increased linearly with increasing dose. The blood glucose levels of all subjects stayed very close to the clamp target until end of clamp. The terminal half-life of IDeg was approximately 25 h at steady state. IDeg was well tolerated and no safety concerns were identified. No injection site reactions were reported. IDeg has a flat and consistent glucose-lowering effect in people with type 2 diabetes. © 2012 Blackwell Publishing Ltd.

[Diagnostic reference levels in interventional radiology].

PubMed

Vañó Carruana, E; Fernández Soto, J M; Sánchez Casanueva, R M; Ten Morón, J I

2013-12-01

This article discusses the diagnostic reference levels for radiation exposure proposed by the International Commission on Radiological Protection (ICRP) to facilitate the application of the optimization criteria in diagnostic imaging and interventional procedures. These levels are normally established as the third quartile of the dose distributions to patients in an ample sample of centers and are supposed to be representative of good practice regarding patient exposure. In determining these levels, it is important to evaluate image quality as well to ensure that it is sufficient for diagnostic purposes. When the values for the dose received by patients are systematically higher or much lower than the reference levels, an investigation should determine whether corrective measures need to be applied. The European and Spanish regulations require the use of these reference values in quality assurance programs. For interventional procedures, the dose area product (or kerma area product) values are usually used as reference values together with the time under fluoroscopy and the total number of images acquired. The most modern imaging devices allow the value of the accumulated dose at the entrance to the patient to be calculated to optimize the distribution of the dose on the skin. The ICRP recommends that the complexity of interventional procedures be taken into account when establishing reference levels. In the future, diagnostic imaging departments will have automatic systems to manage patient dosimetric data; these systems will enable continuous dosage auditing and alerts about individual procedures that might involve doses several times above the reference values. This article also discusses aspects that need to be clarified to take better advantage of the reference levels in interventional procedures. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

Accurate low-dose iterative CT reconstruction from few projections by Generalized Anisotropic Total Variation minimization for industrial CT.

PubMed

Debatin, Maurice; Hesser, Jürgen

2015-01-01

Reducing the amount of time for data acquisition and reconstruction in industrial CT decreases the operation time of the X-ray machine and therefore increases the sales. This can be achieved by reducing both, the dose and the pulse length of the CT system and the number of projections for the reconstruction, respectively. In this paper, a novel generalized Anisotropic Total Variation regularization for under-sampled, low-dose iterative CT reconstruction is discussed and compared to the standard methods, Total Variation, Adaptive weighted Total Variation and Filtered Backprojection. The novel regularization function uses a priori information about the Gradient Magnitude Distribution of the scanned object for the reconstruction. We provide a general parameterization scheme and evaluate the efficiency of our new algorithm for different noise levels and different number of projection views. When noise is not present, error-free reconstructions are achievable for AwTV and GATV from 40 projections. In cases where noise is simulated, our strategy achieves a Relative Root Mean Square Error that is up to 11 times lower than Total Variation-based and up to 4 times lower than AwTV-based iterative statistical reconstruction (e.g. for a SNR of 223 and 40 projections). To obtain the same reconstruction quality as achieved by Total Variation, the projection number and the pulse length, and the acquisition time and the dose respectively can be reduced by a factor of approximately 3.5, when AwTV is used and a factor of approximately 6.7, when our proposed algorithm is used.

Effect of high-dose vs standard-dose multivitamin supplementation at the initiation of HAART on HIV disease progression and mortality in Tanzania: a randomized controlled trial.

PubMed

Isanaka, Sheila; Mugusi, Ferdinand; Hawkins, Claudia; Spiegelman, Donna; Okuma, James; Aboud, Said; Guerino, Chalamilla; Fawzi, Wafaie W

2012-10-17

Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART. To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART. A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance. The composite of HIV disease progression or death from any cause. The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels. Clinicaltrials.gov Identifier: NCT00383669.

Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013.

PubMed

Kyu, Hmwe H; Bachman, Victoria F; Alexander, Lily T; Mumford, John Everett; Afshin, Ashkan; Estep, Kara; Veerman, J Lennert; Delwiche, Kristen; Iannarone, Marissa L; Moyer, Madeline L; Cercy, Kelly; Vos, Theo; Murray, Christopher J L; Forouzanfar, Mohammad H

2016-08-09

 To quantify the dose-response associations between total physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events.  Systematic review and Bayesian dose-response meta-analysis.  PubMed and Embase from 1980 to 27 February 2016, and references from relevant systematic reviews. Data from the Study on Global AGEing and Adult Health conducted in China, Ghana, India, Mexico, Russia, and South Africa from 2007 to 2010 and the US National Health and Nutrition Examination Surveys from 1999 to 2011 were used to map domain specific physical activity (reported in included studies) to total activity.  Prospective cohort studies examining the associations between physical activity (any domain) and at least one of the five diseases studied.  174 articles were identified: 35 for breast cancer, 19 for colon cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic stroke (some articles included multiple outcomes). Although higher levels of total physical activity were significantly associated with lower risk for all outcomes, major gains occurred at lower levels of activity (up to 3000-4000 metabolic equivalent (MET) minutes/week). For example, individuals with a total activity level of 600 MET minutes/week (the minimum recommended level) had a 2% lower risk of diabetes compared with those reporting no physical activity. An increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%. The same amount of increase yielded much smaller returns at higher levels of activity: an increase of total activity from 9000 to 12 000 MET minutes/week reduced the risk of diabetes by only 0.6%. Compared with insufficiently active individuals (total activity <600 MET minutes/week), the risk reduction for those in the highly active category (≥8000 MET minutes/week) was 14% (relative risk 0.863, 95% uncertainty interval 0.829 to 0.900) for breast cancer; 21% (0.789, 0.735 to 0.850) for colon cancer; 28% (0.722, 0.678 to 0.768) for diabetes; 25% (0.754, 0.704 to 0.809) for ischemic heart disease; and 26% (0.736, 0.659 to 0.811) for ischemic stroke.  People who achieve total physical activity levels several times higher than the current recommended minimum level have a significant reduction in the risk of the five diseases studied. More studies with detailed quantification of total physical activity will help to find more precise relative risk estimates for different levels of activity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Management of factor VII-deficient patients undergoing joint surgeries--preliminary results of locally developed treatment regimen.

PubMed

Windyga, J; Zbikowski, P; Ambroziak, P; Baran, B; Kotela, I; Stefanska-Windyga, E

2013-01-01

Inherited factor VII (FVII) deficiency is a rare coagulation disorder with variable haemorrhagic manifestations. In severely affected cases spontaneous haemarthroses leading to advanced arthropathy have been observed. Such cases may require surgery. Therapeutic options for bleeding prevention in FVII deficient patients undergoing surgery comprise various FVII preparations but the use of recombinant activated factor VII (rFVIIa) seems to be the treatment of choice. To present the outcome of orthopaedic surgery under haemostatic coverage of rFVIIa administered according to the locally established treatment regimen in five adult patients with FVII baseline plasma levels below 10 IU dL(-1). Two patients required total hip replacement (THR); three had various arthroscopic procedures. Recombinant activated factor VII was administered every 8 h on day of surgery (D0) followed by every 12-24 h for the subsequent 9-14 days, depending on the type of surgery. Factor VII plasma coagulation activity (FVII:C) was determined daily with no predefined therapeutic target levels. Doses of rFVIIa on D0 ranged from 18 to 37 μg kg(-1) b.w. and on the subsequent days--from 13 to 30 μg kg(-1) b.w. Total rFVIIa dose per procedure ranged from 16 to 37.5 mg, and the total number of doses per procedure was 16-31. None of our patients developed excessive bleeding including those in whom FVII:C trough levels returned nearly to the baseline level on the first post-op day. Preliminary results demonstrate that rFVIIa administered according to our treatment regimen is an effective and safe haemostatic agent for hypoproconvertinaemia patients undergoing orthopaedic surgery. © 2012 Blackwell Publishing Ltd.

Biologically based modeling of multimedia, multipathway, multiroute population exposures to arsenic

PubMed Central

Georgopoulos, Panos G.; Wang, Sheng-Wei; Yang, Yu-Ching; Xue, Jianping; Zartarian, Valerie G.; Mccurdy, Thomas; Özkaynak, Halûk

2011-01-01

This article presents an integrated, biologically based, source-to-dose assessment framework for modeling multimedia/multipathway/multiroute exposures to arsenic. Case studies demonstrating this framework are presented for three US counties (Hunderton County, NJ; Pima County, AZ; and Franklin County, OH), representing substantially different conditions of exposure. The approach taken utilizes the Modeling ENvironment for TOtal Risk studies (MENTOR) in an implementation that incorporates and extends the approach pioneered by Stochastic Human Exposure and Dose Simulation (SHEDS), in conjunction with a number of available databases, including NATA, NHEXAS, CSFII, and CHAD, and extends modeling techniques that have been developed in recent years. Model results indicate that, in most cases, the food intake pathway is the dominant contributor to total exposure and dose to arsenic. Model predictions are evaluated qualitatively by comparing distributions of predicted total arsenic amounts in urine with those derived using biomarker measurements from the NHEXAS — Region V study: the population distributions of urinary total arsenic levels calculated through MENTOR and from the NHEXAS measurements are in general qualitative agreement. Observed differences are due to various factors, such as interindividual variation in arsenic metabolism in humans, that are not fully accounted for in the current model implementation but can be incorporated in the future, in the open framework of MENTOR. The present study demonstrates that integrated source-to-dose modeling for arsenic can not only provide estimates of the relative contributions of multipathway exposure routes to the total exposure estimates, but can also estimate internal target tissue doses for speciated organic and inorganic arsenic, which can eventually be used to improve evaluation of health risks associated with exposures to arsenic from multiple sources, routes, and pathways. PMID:18073786

Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and Inflammatory Response: A Randomized Controlled Trial.

PubMed

Zeng, Wei-Nan; Liu, Jun-Li; Wang, Fu-You; Chen, Cheng; Zhou, Qiang; Yang, Liu

2018-02-21

The reductions of perioperative blood loss and inflammatory response are important in total knee arthroplasty. Tranexamic acid reduced blood loss and the inflammatory response in several studies. However, the effect of epinephrine administration plus tranexamic acid has not been intensively investigated, to our knowledge. In this study, we evaluated whether the combined administration of low-dose epinephrine plus tranexamic acid reduced perioperative blood loss or inflammatory response further compared with tranexamic acid alone. This randomized placebo-controlled trial consisted of 179 consecutive patients who underwent primary total knee arthroplasty. Patients were randomized into 3 interventions: Group IV received intravenous low-dose epinephrine plus tranexamic acid, Group TP received topical diluted epinephrine plus tranexamic acid, and Group CT received tranexamic acid alone. The primary outcome was perioperative blood loss on postoperative day 1. Secondary outcomes included perioperative blood loss on postoperative day 3, coagulation and fibrinolysis parameters (measured by thromboelastography), inflammatory cytokine levels, transfusion values (rate and volume), thromboembolic complications, length of hospital stay, wound score, range of motion, and Hospital for Special Surgery (HSS) score. The mean calculated total blood loss (and standard deviation) in Group IV was 348.1 ± 158.2 mL on postoperative day 1 and 458.0 ± 183.4 mL on postoperative day 3, which were significantly reduced (p < 0.05) compared with Group TP at 420.5 ± 188.4 mL on postoperative day 1 and 531.1 ± 231.4 mL on postoperative day 3 and Group CT at 520.4 ± 228.4 mL on postoperative day 1 and 633.7 ± 237.3 mL on postoperative day 3. Intravenous low-dose epinephrine exhibited a net anti-inflammatory activity in total knee arthroplasty and did not induce an obvious hypercoagulable status. Transfusion values were significantly reduced (p < 0.05) in Group IV, but no significant differences were observed in the incidence of thromboembolic complications, wound score, range of motion, and HSS score among the 3 groups (p > 0.05). The combined administration of low-dose epinephrine and tranexamic acid demonstrated an increased effect in reducing perioperative blood loss and the inflammatory response compared with tranexamic acid alone, with no apparent increased incidence of thromboembolic and other complications. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats.

PubMed

Cheng, Chen; Lin, Jia-zhen; Li, Li; Yang, Jun-ling; Jia, Wei-wei; Huang, Yu-hong; Du, Fei-fei; Wang, Feng-qing; Li, Mei-juan; Li, Yan-fen; Xu, Fang; Zhang, Na-ting; Olaleye, Olajide E; Sun, Yan; Li, Jian; Sun, Chang-hai; Zhang, Gui-ping; Li, Chuan

2016-04-01

Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001-2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2-1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.

Evaluation of Aqueous Leaf Extract of Cardiospermum halicacabum (L.) on Fertility of Male Rats.

PubMed

Peiris, L Dinithi C; Dhanushka, M A T; Jayathilake, T A H D G

2015-01-01

Treatment with 100 mg/kg and 200 mg/kg body weight of aqueous leaf extract (ALE) of Cardiospermum halicacabum for 30 days produced a significant dose dependent increase in the sperm counts and sperm motility in both caput and cauda regions. Further, significant increase in serum testosterone level was evident at all applied doses. However, no significant changes in the weight of sex organs were observed. Aqueous leaf extract also increased the number of females impregnated, number of implantations, and number of viable fetuses while decreasing the total number of resorption sites in the pregnant females. However, the total cholesterol level in the serum remained unchanged and there were no records on renotoxicity; nevertheless ALE exhibited a hepatoprotective effect. It was concluded that aqueous leaf extract of Cardiospermum halicacabum enhanced sperm concentration, motility, and testosterone, leading to positive results in fertility.

Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer

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

Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp; Kamada, Tadashi; Ebner, Daniel K.

Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results: Duringmore » phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.« less

Burosumab Therapy in Children with X-Linked Hypophosphatemia.

PubMed

Carpenter, Thomas O; Whyte, Michael P; Imel, Erik A; Boot, Annemieke M; Högler, Wolfgang; Linglart, Agnès; Padidela, Raja; Van't Hoff, William; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Kakkis, Emil; San Martin, Javier; Portale, Anthony A

2018-05-24

X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ).

A phase I study of amrubicin and fixed dose of irinotecan (CPT-11) in relapsed small cell lung cancer: Japan multinational trial organization LC0303.

PubMed

Kawahara, Masaaki; Kubo, Akihito; Komuta, Kiyoshi; Fujita, Yuka; Sasaki, Yoshiaki; Fukushima, Masanori; Daimon, Takashi; Furuse, Kiyoyuki; Mishima, Michiaki; Mio, Tadashi

2012-12-01

To determine the maximum tolerated dose of amrubicin (AMR) with a fixed dose of irinotecan (CPT-11). Patients having pathologically proven small cell lung cancer (SCLC) relapsed after one or two chemotherapies, and Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible for the study. CPT-11 was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80 mg/m2, level 2: 90 mg/m2, and level 3: 100 mg/m2. Dose elevation was determined using the modified continuous reassessment method. Tolerability was assessed after the first cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Eighteen patients (mean age: 66.3 years) were enrolled. A total of 40 courses were conducted. Grade 3/4 toxicities of the first cycle were leukocytopenia: 11 (61%, grade 3/4: 8/3); neutropenia: 15 (83%, grade 3/4: 6/9); and thrombocytopenia: three (17%, grade 3/4: 2/1). Other grade 3 toxicities observed were febrile neutropenia, one; infection, three; diarrhea, one; and dyspnea, one. Dose-limiting toxicity was observed in two of six patients at level 2 (neutropenia and febrile neutropenia) and in one of six at level 3 (thrombocytopenia and infection). The maximum tolerated dose was level 3, and so, the recommended dose for phase II trials was judged to be 90 mg/m2. Objective response was obtained in four of eight patients who were able to evaluate responses. Median survival time was 13 months, with 68% at 1-year survival rate. This combination was well tolerated and showed encouraging activities in SCLC. Randomized phase II trials are being planned in chemonaive SCLC.

Modified BEAM with triple autologous stem cell transplantation for patients with relapsed aggressive non-Hodgkin lymphoma.

PubMed

Hohloch, Karin; Zeynalova, Samira; Chapuy, Björn; Pfreundschuh, Michael; Loeffler, Markus; Ziepert, Marita; Feller, Alfred C; Trümper, Lorenz; Hasenclever, Dirk; Wulf, Gerald; Schmitz, Norbert

2016-06-01

Treatment of relapse and primary progression in aggressive lymphoma remains unsatisfactory; outcome is still poor. Better treatment strategies are much needed for this patient population. The R1 study is a prospective multi-center phase I/II study evaluating a dose finding approach with a triple transplant regimen in four BEAM dose levels in patients with relapsed aggressive non-Hodgkin lymphoma. The aim of the study was to determine feasibility, toxicity, and remission rate. In a total of 39 patients (pts.) enrolled in the study, 24 pts. were evaluated in the following analysis. Twenty pts. had aggressive B cell lymphoma, and two pts. had T cell lymphoma. All evaluated patients responded to DexaBEAM with a sufficient stem cell harvest. The phase I/II study was started with BEAM dose level II. Four patients were treated at dose level II, and 20 pts. were treated at dose level III. Due to the early termination of the study, dose levels I and IV were never administered. Sixteen pts. completed therapy according to protocol, and eight pts. (33.3 %) stopped treatment early. Infections (27 %) and stomatitis (13 %) were the most frequent grade III/IV non-hematologic toxicities. Thirteen percent of patients presented with severe grade III/IV lung toxicity during modified BEAM (m-BEAM). Fourteen pts. achieved a complete response (CR), one pt. achieved no change (NC), six pts. had progressive disease (PD), and two pts. died; for one pt., outcome is not known. One-year and 3-year event-free survival (EFS) was 38 and 33 %, respectively. Overall survival (OS) after 1 and 3 years was 50 and 38 %. In conclusion, dose escalation of standard BEAM is not feasible due to toxicity.

The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics

PubMed Central

Formgren, H.

1976-01-01

1 The effect of metoprolol, a new β1-adrenoceptor blocking agent, was compared to practolol in the treatment of hypertension in seventeen asthmatics during concurrent optimum bronchodilator therapy with a selective β2-adrenoceptor-stimulant. 2 The two β-adrenoceptor antagonists were given at two dose levels, practolol (200 mg and 400 mg) daily, and metoprolol (100 mg and 200 mg) daily, in a twice-daily dosage schedule, at 12 h intervals, for 17 days. The comparison was made double-blind and a crossover design was used. The drugs were given in randomized order. The study started with a run-in placebo period and there was a washout period on placebo between the treatment periods. Spirometry, blood pressures and heart rates were recorded in a standardized manner. 3 At the lower dose levels no influence on FEV1 was noted, and no difference was found between the two active drugs. At the higher dose level FEV1 was reduced by both β-adrenoceptor-blocking drugs. Four out of twelve patients given the higher dose experienced exacerbation of their asthma. The heart rate fell with both drugs and at both dose levels. During the placebo period a marked increase of heart rate was noted. The blood pressure fell at both dose levels compared to placebo, no difference being recorded between the two drugs. 4 Metoprolol and practolol are equally effective β1-adrenoceptor blocking drugs. In this study it was found that metoprolol could be used in asthmatics who had indications for β-adrenoceptor blockade, provided that the total daily dose did not exceed 100 mg. Optimal bronchodilator treatment with a bronchoselective β-adrenoceptor agonist is an absolute prerequisite in order to avoid the risk of aggravation of asthma. PMID:22216522

SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

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

Chen, Y; Souri, S; Gill, G

Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose tomore » its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.« less

[Usefulness of Bolus Administration Using the FLEX Mode(Bolus Infusion Mode)for Baclofen Tolerance].

PubMed

Tanaka, Kazunori

2017-02-01

Intrathecal baclofen(ITB)is used to treat intractable spasticity of various etiologies and can provide better control of spasticity through the adjustment of the dose administered through the pump. However, in patients who develop tolerance to baclofen with the standard simple continuous mode, a sharp increase in dose becomes necessary, and spasticity can become harder to control. We investigated whether switching from the simple continuous mode to the bolus infusion mode was effective in controlling spasticity in patients with baclofen tolerance. We reported four patients undergoing ITB therapy at our facility who were considered to have developed baclofen tolerance. We observed the number of bolus infusions and total dose suitable for maintaining spasticity control after switching from the simple continuous mode to the bolus infusion mode. After switching to the bolus infusion mode, the total dose could be reduced in the short term; however, in the long term, the frequency of bolus infusions had to be increased to maintain spasticity control. Two years after changing to bolus infusion six times a day, the total dose was higher than that in the simple continuous mode for two of the four patients, and was the same level in the other two patients. Our four cases suggest that bolus infusion is effective in patients with baclofen tolerance during ITB therapy. Therefore, the conditions of bolus infusion should be further investigated.

Study of runaway electrons using dosimetry of hard x-ray radiations in Damavand tokamak

NASA Astrophysics Data System (ADS)

Rasouli, C.; Pourshahab, B.; Hosseini Pooya, S. M.; Orouji, T.; Rasouli, H.

2014-05-01

In this work several studies have been conducted on hard x-ray emissions of Damavand tokamak based on radiation dosimetry using the Thermoluminescence method. The goal was to understand interactions of runaway electrons with plasma particles, vessel wall, and plasma facing components. Total of 354 GR-200 (LiF:Mg,Cu,P) thermoluminescence dosimeter (TLD) crystals have been placed on 118 points - three TLDs per point - to map hard x-ray radiation doses on the exterior of the vacuum vessel. Results show two distinctive levels of x-ray radiations doses on the exterior of the vessel. The low-dose area on which measured dose is about 0.5 mSv/shot. In the low-dose area there is no particular component inside the vessel. On the contrary, on high-dose area of the vessel, x-ray radiations dose exceeds 30 mSv/shot. The high-dose area coincides with the position of limiters, magnetic probe ducts, and vacuum vessel intersections. Among the high-dose areas, the highest level of dose is measured in the position of the limiter, which could be due to its direct contact with the plasma column and with runaway electrons. Direct collisions of runaway electrons with the vessel wall and plasma facing components make a major contribution for production of hard x-ray photons in Damavand tokamak.

Study of runaway electrons using dosimetry of hard x-ray radiations in Damavand tokamak.

PubMed

Rasouli, C; Pourshahab, B; Hosseini Pooya, S M; Orouji, T; Rasouli, H

2014-05-01

In this work several studies have been conducted on hard x-ray emissions of Damavand tokamak based on radiation dosimetry using the Thermoluminescence method. The goal was to understand interactions of runaway electrons with plasma particles, vessel wall, and plasma facing components. Total of 354 GR-200 (LiF:Mg,Cu,P) thermoluminescence dosimeter (TLD) crystals have been placed on 118 points--three TLDs per point--to map hard x-ray radiation doses on the exterior of the vacuum vessel. Results show two distinctive levels of x-ray radiations doses on the exterior of the vessel. The low-dose area on which measured dose is about 0.5 mSv/shot. In the low-dose area there is no particular component inside the vessel. On the contrary, on high-dose area of the vessel, x-ray radiations dose exceeds 30 mSv/shot. The high-dose area coincides with the position of limiters, magnetic probe ducts, and vacuum vessel intersections. Among the high-dose areas, the highest level of dose is measured in the position of the limiter, which could be due to its direct contact with the plasma column and with runaway electrons. Direct collisions of runaway electrons with the vessel wall and plasma facing components make a major contribution for production of hard x-ray photons in Damavand tokamak.

The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child.

PubMed

Orr, J M; Farrell, K; Abbott, F S; Ferguson, S; Godolphin, W J

1983-01-01

The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.

[Effect of low-dose or standard-dose conjugated equine estrogen combined with different progesterone on bone density in menopause syndrome women].

PubMed

Zuo, H L; Deng, Y; Wang, Y F; Gao, L L; Xue, W; Zhu, S Y; Ma, X; Sun, A J

2018-04-25

Objective: To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE) combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women. Methods: Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A (low-dose CEE+progesterone) , group B (standard-dose CEE+progesterone) , group C (standard-dose CEE+dydrogesterone) . Using continuous sequential regimen, the duration of intervention was 12 cycles. The bone mineral density of lumbar 2-4 and neck of femur, the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results: There were 107 cases completed the one year trial. (1) Bone density: after 12 cycles of treatment, there was no significant change in bone density in group A ( P> 0.05) ; lumbar vertebrae of group B and C increased significantly, at 3.0% and 2.1%respectively (all P< 0.05) . The bone density of left femoral neck of group C significantly increased by 2.9% ( P= 0.029) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (2) Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly, the difference were statistically significant (all P< 0.05) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (3) Levels of FSH and estradiol: after 12 cycles of treatment, the levels of FSH in three groups were decreased significantly (all P< 0.01) . The levels of estradiol in three groups were increased significantly (all P< 0.01) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . Conclusions: Both low-dose and standard-dose menopause hormone therapy (MHT) could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck, and generate more clinical benefits.

Salicylate-induced enzymuria: comparison with other anti-inflammatory agents.

PubMed

Proctor, R A; Kunin, C M

1978-12-01

N-acetyl-beta glucosaminidase (NAG) enzymuria was used as a marker of renal injury in patients with rheumatic disease. An elevated NAG level was particularly common in patients receiving gold or aspirin therapy. The multiplicity of drugs received and the unknown role of underlying disease in these patients led to a study in healthy volunteers. Customary therapeutic doses of aspirin, choline salicylate, ibuprofen, indomethacin and acetaminophen did not produce enzymuria. Large single doses of salicylates equivalent to 6 tablets of aspirin consistently did produce enzymuria. The size of the individual dose in relation to body weight was more important than the total daily dose. NAG enzymuria appears to be a sensitive tool for identifying potentially nephrotoxic drugs.

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

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

Storb, R.; Raff, R.F.; Graham, T.

1993-03-20

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionatedmore » total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.« less

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

PubMed

Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

2017-08-15

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017. Published by Elsevier B.V.

RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

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

Chinnaiyan, Prakash, E-mail: prakash.chinnaiyan@moffitt.org; Won, Minhee; Wen, Patrick Y.

Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established dailymore » dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.« less

Glutamine Provides Effective Protection against Deltamethrin-Induced Acute Hepatotoxicity in Rats But Not Against Nephrotoxicity

PubMed Central

Gündüz, Ercan; Ülger, Burak Veli; İbiloğlu, İbrahim; Ekinci, Aysun; Dursun, Recep; Zengin, Yılmaz; İçer, Mustafa; Uslukaya, Ömer; Ekinci, Cenap; Güloğlu, Cahfer

2015-01-01

Background The aim of this study was to investigate the protective effects of L-glutamine (GLN) against liver and kidney injury caused by acute toxicity of deltamethrin (DLM). Material/Methods Thirty-two rats were indiscriminately separated into 4 groups with 8 rats each: control group (distilled water; 10 ml/kg, perorally [p.o.]), DLM group (35 mg/kg p.o. one dose.), GLN group (1.5 gr/kg, p.o. single dose.) and DLM (35 mg/kg p.o. one dose.) + GLN group (1.5 gr/kg, p.o. one dose after 4 hours.). Testing for total antioxidant status (TAS), total oxidant status (TOS), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) analyses were performed on tissue samples, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), urea, and creatinine were analyzed on serum samples. Liver and kidney samples were histopathologically analyzed. Results The TOS level in liver was significantly higher in the DLM group than in the control group, and the level in DLM+GLN group was considerably lower than in the DLM group. The TAS level in the DLM+GLN group was considerably higher than in the control and DLM groups. The TAS level in kidney tissues was considerably lower in the DLM group than in controls, but was similar to other groups. Histopathological analyses of liver tissues established a significant difference between DLM and DLM+GLN groups in terms of grade 2 hepatic injury. However, no significant difference was found between DLM and DLM+GLN groups in terms of kidney injury. Conclusions Glutamine leads to significant improvement in deltamethrin-induced acute hepatotoxicity in terms of histopathologic results, tissue oxidative stress parameters, and serum liver function marker enzymes. PMID:25890620

Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I.

PubMed

Kakkis, E; McEntee, M; Vogler, C; Le, S; Levy, B; Belichenko, P; Mobley, W; Dickson, P; Hanson, S; Passage, M

2004-01-01

Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood-brain barrier on enzyme distribution. To circumvent this barrier, we studied whether intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the brain and meninges. An initial dose-response study showed that doses of 0.46-4.14 mg of IT rhIDU successfully penetrated the brain of normal dogs and reached tissue levels 5.6 to 18.9-fold normal overall and 2.7 to 5.9-fold normal in deep brain sections lacking CSF contact. To assess the efficacy and safety in treating lysosomal storage disease, four weekly doses of approximately 1 mg of IT rhIDU were administered to MPS I-affected dogs resulting in a mean 23- and 300-fold normal levels of iduronidase in total brain and meninges, respectively. Quantitative glycosaminoglycan (GAG) analysis showed that the IT treatment reduced mean total brain GAG to normal levels and achieved a 57% reduction in meningeal GAG levels accompanied by histologic improvement in lysosomal storage in all cell types. The dogs did develop a dose-dependent immune response against the recombinant human protein and a meningeal lymphocytic/plasmacytic infiltrate. The IT route of ERT administration may be an effective way to treat the CNS disease in MPS I and could be applicable to other lysosomal storage disorders.

Gamma irradiation to improve plant vigour, grain development, and yield attributes of wheat

NASA Astrophysics Data System (ADS)

Singh, Bhupinder; Datta, P. S.

2010-02-01

Utilizing low dose gamma radiation holds promise for physiological crop improvement. Seed treatment of low dose gamma radiation 0.01-0.10 kGy reduced plant height, improved plant vigour, flag leaf area, total and number of EBT. Gamma irradiation increased grain yield due to an increase in number of EBT and grain number while 1000 grain weight was negatively affected. Further uniformity in low dose radiation response in wheat in the field suggests that the affect is essentially at physiological than at genetic level and that role of growth hormones could be crucial.

Predictors of Local Control After Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases

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

Greco, Carlo; Zelefsky, Michael J., E-mail: zelefskm@mskcc.or; Lovelock, Michael

2011-03-15

Purpose: To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites. Methods and Materials: A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007. Results: The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy),more » intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses ({<=}22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003). Conclusion: High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered.« less

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

PubMed

Ray, Kausik K; Landmesser, Ulf; Leiter, Lawrence A; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P T; Turner, Traci; Visseren, Frank L J; Wijngaard, Peter; Wright, R Scott; Kastelein, John J P

2017-04-13

In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers. We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240. A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran. In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127 .).

Voluntarily exposure to a single, high dose of probiotic Escherichia coli results in prolonged colonisation.

PubMed

Wassenaar, T M; Beimfohr, C; Geske, T; Zimmermann, K

2014-12-01

The ability of probiotic Escherichia coli to colonise the human gut was determined in a volunteer study following national (German) regulations. Five persons voluntarily took a single, high dose of Symbioflor®2, which contains 6 different probiotic E. coli genotypes, to assess tolerance of the product, after which presence of E. coli in their faeces was tested for a follow-up period of 30 weeks. Intake of the product did not result in severe side effect in any of the individuals, though mild side effects were observed. Stool analysis showed that the probiotic E. coli had colonised all five persons for a period of 10 to 30 weeks (mean: 18.7 weeks, median: 25.7 weeks). In two individuals there was evidence of competition between host E. coli and probiotic E. coli, while in two others total E. coli levels increased persistently with at least a factor of 10 as a result of the received dose. In one individual, who had lacked detectable levels of faecal E. coli at the start of the post-authorisation safety study, long-term colonisation was established, first by probiotic E. coli exclusively, which were later replaced by host E. coli strains. In four out of five individuals, total E. coli faecal counts were higher on average than at the start of the experiment, while in none total levels exceeded 5×107 cfu/g. When the specific genotypes of the 6 probiotic E. coli were analysed, it was found that one and the same common genotype was responsible for prolonged colonisation in all five individuals.

Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

PubMed Central

Ahmad, Feroz; Tabassum, Nahida

2013-01-01

Objective To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Methods Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Result Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. Conclusions The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential. PMID:23570019

Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test

PubMed Central

Hu, Yi-Min; Zhou, Zhi-Qiang; Zhang, Guang-Fen

2013-01-01

Introduction Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR). Methods Forty male Wistar rats weighing 180–220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels. Results Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses) Conclusion The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats. PMID:22970723

Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test.

PubMed

Yang, Chun; Hu, Yi-Min; Zhou, Zhi-Qiang; Zhang, Guang-Fen; Yang, Jian-Jun

2013-03-01

Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR). Forty male Wistar rats weighing 180-220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels. Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses) The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats.

Dose- dependent ameliorative effects of quercetin and l-Carnitine against atrazine- induced reproductive toxicity in adult male Albino rats.

PubMed

Abdel Aziz, Rabie L; Abdel-Wahab, Ahmed; Abo El-Ela, Fatma I; Hassan, Nour El-Houda Y; El-Nahass, El-Shaymaa; Ibrahim, Marwa A; Khalil, Abdel-Tawab A Y

2018-06-01

This study aimed to determine the protective effects of co-administration of Quercetin (QT) or l-Carnitine (LC) against the oxidative stress induced by Atrazine (ATZ) in the reproductive system of intact male Albino rats. 36 rats were divided equally into 6 groups. Rats in the control negative "CNT" group received 1.5 ml distilled water for 21 days. All rats in the other groups received ATZ (120 mg/kg bw) through gavage. Groups 3 and 4 were co-administered with either low or high dose of QT (10 "ATZLQT" and 50 "ATZHQT" mg/kg bw, respectively). Groups 5 and 6 were co-administered with either low or high dose of LC (200 "ATZLLC" and 400 "ATZHLC" mg/kg bw, respectively). At the end of the experiment, animals were sacrificed and all samples were collected. ATZ significantly increased serum level of malondialdehyde (MDA) and decreased total antioxidant capacity (TAC). Also, ATZ increased significantly the sperm cell abnormalities and reduced both testicular IgA and serum testosterone levels. Testicular DNA laddering % and CYP17A1 mRNA expression were significantly reduced in ATZ group. Interestingly, co-administration with low dose QT or different doses of LC succeeded to counteract the negative toxic effects of ATZ on serum oxidative stress indicators, serum testosterone levels, testicular IgA level and improved testicular CYP17A1 mRNA expression. In conclusion, QT in low dose and LC in both low and high doses exerted a significant protective action against the reproductive toxicity of ATZ, while higher dose of QT failed induce immune-stimulant effect against ATZ in adult male Albino rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Use of remifentanil to reduce propofol injection pain and the required propofol dose in upper digestive tract endoscopy diagnostic tests.

PubMed

Uliana, Gustavo Nadal; Tambara, Elizabeth Milla; Baretta, Giorgio Alfredo Pedroso

2015-01-01

The introduction of propofol (2,6-diisopropylphenol) as a sedative agent has transformed the area of sedation for endoscopic procedures. However, a major drawback of sedation with the use of propofol is its high incidence of injection pain. The most widely used technique in reducing propofol injection pain is through the association of other drugs. The aim of this study was to evaluate the effect of remifentanil-propofol combination on the incidence of propofol injection pain and its influence on the total dose of propofol required for sedation in upper digestive tract endoscopy (UDE) diagnostic tests. One hundred and five patients undergoing upper digestive tract endoscopy were evaluated and randomly divided into 3 groups of 35 patients each. The Control Group received propofol alone; Study-group 1 received remifentanil at a fixed dose of 0.2mg/kg combined with propofol; Study-group 2 received remifentanil at a fixed dose of 0.3mg/kg combined with propofol. The incidence of propofol injection pain and the total dose of propofol required for the test were evaluated. The sample was very similar regarding age, weight, height, sex, and physical status. Statistical analysis was performed according to the nature of the evaluated data. Student's t-test was used to compare the mean of age, weight, height (cm), and dose (mg/kg) variables between groups. The χ(2) test was used to compare sex, physical status, and propofol injection pain between groups. The significance level was α<0.05. There was significant statistical difference between the study groups and the control group regarding the parameters of propofol injection pain and total dose of propofol (mg/kg) used. However, there were no statistical differences between the two study groups for these parameters. We conclude that the use of remifentanil at doses of 0.2mg/kg and 0.3mg/kg was effective for reducing both the propofol injection pain and the total dose of propofol used. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

SOME CHANGES IN THE CARBOHYDRATE METABOLISM AND THE ALBUMIN FRACTION OF THE BLOOD SERUM OF RABBITS IN CASE OF CHRONIC TREATMENT WITH IRON-59 (in Russian)

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

Orlyanskaya, R.L.

1962-01-01

A study was undertaken to determine the effect of chronic daily poisoning of rabbits with Fe/sup 59/on the sugar content of the blood, the albumin fraction, and the total albumin content after treatment with glucose. The results indicated that daily administration of 1 and 10 mu C/kg of body weight of Fe/sup 59/ for a total of 16 months causes only a slight change in the level of the blood sugar; only a chronic exposure to the higher dose resulted in a slight reduction in the sugar level. These animals also exhibited a tendency toward hypoglycemia. No changes were notedmore » in the total albumin content of the serum. Exposure to the higher dose for 6 months caused a reduction of the albumin fraction and a corresponding increase of the globulin content. The A/G ratio was found to decrease first, followed by an increase after a few months. (TTT)« less

Toxic influence of key organic soil pollutants on the total flavonoid content in wheat leaves

PubMed Central

Copaciu, Florina; Opriş, Ocsana; Niinemets, Ülo; Copolovici, Lucian

2018-01-01

Textile dyes and antibiotics are two main classes of environmental pollutants which could be found in soil and water. Those persistent pollutants can have a negative influence on plant growth and development and affect the level of secondary metabolites. In the present work we studied the effect of textile dyes and antibiotics on total leaf flavonoid contents in wheat (Triticum aestivum L.). Contaminant solutions were applied daily using concentrations of 0.5 mg L–1 (lower) and 1.5 mg L–1 (higher dose) for either one or two weeks. We observed that exposure to the higher concentration of textile dyes resulted in a reduction in flavonoid content while antibiotics enhanced flavonoid contents at lower doses of exposure, and reduced at higher doses of exposure. These results suggest that diffuse chronic pollution by artificial organic contaminants can importantly alter antioxidative capacity of plants. PMID:29386693

p-MOSFET total dose dosimeter

NASA Technical Reports Server (NTRS)

Buehler, Martin G. (Inventor); Blaes, Brent R. (Inventor)

1994-01-01

A p-MOSFET total dose dosimeter where the gate voltage is proportional to the incident radiation dose. It is configured in an n-WELL of a p-BODY substrate. It is operated in the saturation region which is ensured by connecting the gate to the drain. The n-well is connected to zero bias. Current flow from source to drain, rather than from peripheral leakage, is ensured by configuring the device as an edgeless MOSFET where the source completely surrounds the drain. The drain junction is the only junction not connected to zero bias. The MOSFET is connected as part of the feedback loop of an operational amplifier. The operational amplifier holds the drain current fixed at a level which minimizes temperature dependence and also fixes the drain voltage. The sensitivity to radiation is made maximum by operating the MOSFET in the OFF state during radiation soak.

Toxic influence of key organic soil pollutants on the total flavonoid content in wheat leaves.

PubMed

Copaciu, Florina; Opriş, Ocsana; Niinemets, Ülo; Copolovici, Lucian

2016-06-01

Textile dyes and antibiotics are two main classes of environmental pollutants which could be found in soil and water. Those persistent pollutants can have a negative influence on plant growth and development and affect the level of secondary metabolites. In the present work we studied the effect of textile dyes and antibiotics on total leaf flavonoid contents in wheat ( Triticum aestivum L.). Contaminant solutions were applied daily using concentrations of 0.5 mg L -1 (lower) and 1.5 mg L -1 (higher dose) for either one or two weeks. We observed that exposure to the higher concentration of textile dyes resulted in a reduction in flavonoid content while antibiotics enhanced flavonoid contents at lower doses of exposure, and reduced at higher doses of exposure. These results suggest that diffuse chronic pollution by artificial organic contaminants can importantly alter antioxidative capacity of plants.

Vocal Dose Measures: Quantifying Accumulated Vibration Exposure in Vocal Fold Tissues

PubMed Central

Titze, Ingo R.; Švec, Jan G.; Popolo, Peter S.

2011-01-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses. PMID:12959470

Vocal dose measures: quantifying accumulated vibration exposure in vocal fold tissues.

PubMed

Titze, Ingo R; Svec, Jan G; Popolo, Peter S

2003-08-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses.

Mobile phone use, school electromagnetic field levels and related symptoms: a cross-sectional survey among 2150 high school students in Izmir.

PubMed

Durusoy, Raika; Hassoy, Hür; Özkurt, Ahmet; Karababa, Ali Osman

2017-06-02

Health outcomes of electromagnetic fields (EMF) from mobile phones and their base stations are of concern. Conducting multidisciplinary research, targeting children and exploring dose-response are recommended. Our objectives were to describe the mobile phone usage characteristics of high school students and to explore the association between mobile phone usage characteristics, high school EMF levels and self-reported symptoms. This cross-sectional study's data were collected by a survey questionnaire and by measuring school EMF levels between November 2009 and April 2011. A sample size of 2530 was calculated from a total of 20,493 students in 26 high schools and 2150 (85.0%) were included in the analysis. The frequencies of 23 symptoms were questioned and analysed according to 16 different aspects of mobile phone use and school EMF levels, exploring also dose-response. School EMF levels were measured with Aaronia Spectran HF-4060 device. Chi square and trend tests were used for univariate and logistic regression was used for multivariate analyses. Among participants, 2021 (94.0%) were using mobile phones and 129 (6.0%) were not. Among users, 49.4% were speaking <10 min and 52.2% were sending/receiving 75 or more messages per day. Headache, fatigue and sleep disturbances were observed respectively 1.90 (95% CI 1.30-2.77), 1.78 (1.21-2.63) and 1.53 (1.05-2.21) times more among mobile phone users. Dose-response relationships were observed especially for the number of calls per day, total duration of calls per day, total number of text messages per day, position and status of mobile phone at night and making calls while charging as exposures and headache, concentration difficulties, fatigue and sleep disturbances as general symptoms and warming of the ear and flushing as local symptoms. We found an association between mobile phone use and especially headache, concentration difficulties, fatigue, sleep disturbances and warming of the ear showing also dose-response. We have found limited associations between vicinity to base stations and some general symptoms; however, we did not find any association with school EMF levels. Decreasing the numbers of calls and messages, decreasing the duration of calls, using earphones, keeping the phone away from the head and body and similar precautions might decrease the frequencies or prevalence of the symptoms.

Green tea (Camellia sinensis) administration induces expression of immune relevant genes and biochemical parameters in rainbow trout (Oncorhynchus mykiss).

PubMed

Nootash, Shahab; Sheikhzadeh, Najmeh; Baradaran, Behzad; Oushani, Ali Khani; Maleki Moghadam, Mohammad Reza; Nofouzi, Katayoon; Monfaredan, Amir; Aghebati, Leili; Zare, Fatemeh; Shabanzadeh, Sadigheh

2013-12-01

Present study elucidates the efficacy of green tea (Camellia sinensis) on growth performance, immune and antioxidant systems and cytokine gene expression in rainbow trout tissues. Green tea was supplemented at 20, 100, and 500 mg kg(-1) diet and fed to fish (average weight: 23.5 g) for 35 days. No remarkable changes in growth performance were observed among all test groups. Lower lipid peroxidation product and higher superoxide dismutase activity were noted in fish received the medium dose of green tea. Significant increase in serum bactericidal activity and total protein were recorded in all treatment groups. All doses of green tea up-regulated Interleukin-1β transcription in the spleen, while Interleukin-1β mRNA level decreased significantly in the kidney of low dose of green tea. Interleukin-6 mRNA level was up-regulated in the spleen of high dose of green tea and liver of middle and high doses of green tea. High dose and medium dose of green tea up-regulated the interleukin-8 transcription in the kidney and liver, respectively. Meanwhile, green tea inhibited the production of interleukin-10 in all treatment groups compared with control group. Medium dose of green tea up-regulated tumor necrosis factor-α transcription in all fish tissues, while high dose and low dose of green tea enhanced tumor necrosis factor-α mRNA levels in the kidney and spleen, respectively. Present study suggests that green tea especially at 100 mg kg(-1) feed may effectively enhance the antioxidant system and immune system in rainbow trout. Copyright © 2013 Elsevier Ltd. All rights reserved.

Potent therapeutic effects of shouwu jiangqi decoction on polycystic ovary syndrome with insulin resistance in rats.

PubMed

Wang, Li-hong; Wang, Xu; Yu, Xi-zhong; Xu, Wen-ting

2016-02-01

To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms. A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups. FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05). SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

Phase I Study of Oxaliplatin in Combination With Capecitabine and Radiotherapy as Postoperative Treatment for Stage II and III Rectal Cancer

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

Jin Jing; Li Yexiong; Wang Jinwan

Purpose: A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin (OXA) combined with capecitabine and radiotherapy as adjuvant treatment in patients with operable rectal cancer. Patients and Methods: A total of 21 patients with Stage II or III rectal adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 50 Gy in 5 weeks. OXA was administered at a dosage of 40 (n = 6), 50 (n = 3),60 (n = 3), 70 (n = 3), or 80 mg/m{sup 2} (n = 6) once a week formore » 2 weeks (first cycle) followed by a second cycle after a 7-day break. Capecitabine at a fixed dose of 1,300 mg/m{sup 2}/d was administered orally at the same schedule as for OXA. DLT was defined as Grade 3 or 4 hematologic and nonhematologic toxicity. Results: Grade 1-3 leukopenia, diarrhea, and nausea/vomiting were the most common toxic side effects, and most were Grade 1-2. A DLT was first observed in 1 of 3 patients at 40 mg/m{sup 2} (Grade 3 diarrhea) but was not observed in the next 3 patients at the same level or in patients who received a dose level of 50-70 mg/m{sup 2}. At 80 mg/m{sup 2}, DLT occurred in 3 of 6 patients (1 Grade 4 leukopenia and 2 Grade 3 diarrhea). Conclusions: OXA combined with a fixed dose of capecitabine at 625 mg/m{sup 2} twice daily by mouth plus radiotherapy in the adjuvant setting was tolerable and clinically feasible. The maximal tolerated dose of OXA in this setting was 80 mg/m{sup 2}, comparable to the maximal tolerated dose of OXA in the neoadjuvant setting.« less

The dependence of the growth rate and meat content of young boars on semen parameters and conception rate.

PubMed

Knecht, D; Jankowska-Mąkosa, A; Duziński, K

2017-05-01

Boars have a decisive impact on the progress in pig production, however, there is no recent information about the optimal growth parameters during the rearing period for modern breed later used in artificial insemination (AI) stations. Therefore, the objective of the research was to conduct semen parameter and conception rate analyses on the basis of growth rate and meat content assessments made during the rearing of AI boars of different genotypes. The study was carried out between 2010 and 2014 and included 184 boars in five breed combinations: 46 Polish Large White, 50 Polish Landrace, 27 Pietrain, 36 Duroc×Pietrain and 25 Hampshire×Pietrain. Boars were qualified by daily gains and meat content assessment (between 170 and 210 days of life). A total number of 38 272 ejaculates were examined (semen volume (ml), spermatozoa concentration (×106 ml-1), total number of spermatozoa (×109) and number of insemination doses from one ejaculate (n)). The fertility was determined by the conception rate (%). Semen volume, spermatozoa concentration and conception rate (P<0.01), followed by the total number of spermatozoa and insemination doses (P<0.05) were characterized by the highest variability in relation to breed of boars. The effect of daily gains was reported for spermatozoa concentration, number of insemination doses, conception rate (all P<0.01) and total number of spermatozoa (P<0.05). The peak of growth for spermatozoa concentration, total number of spermatozoa, insemination doses and conception rate was achieved for 800 to 850 g gains. Meat content affected semen volume, number of insemination doses and conception rate (P<0.05). Rearing boars while maintaining daily gains at the 800 to 850 g level and 62.5% to 65% meat content helps AI stations to increase the efficiency and economic profitability, and the number of insemination doses to increase by up to 300 doses/boar within a year. The analyses of growth parameters may help increase the efficiency and economic viability of AI stations.

A phase I study of WR-2721 in combination with total body irradiation (TBI) in patients with refractory lymphoid malignancies

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

Coia, L.; Krigel, R.; Hanks, G.

This Phase I study was designed to establish the maximum tolerated dose (MTD) of WR-2721 when given twice weekly with total body irradiation (TBI) in the treatment of patients with advanced refractory lymphoid malignancies and to define the toxicities of this combination and schedule. Patients eligible for this study had advanced recurrent indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Patients had symptomatic or progressive disease, a performance status of 0, 1, or 2, and adequate bone marrow, hepatic, and renal function. Only patients failing one or two regimens of prior chemotherapy were eligible. Patients who had received priormore » extended field irradiation were ineligible. Patients received TBI twice weekly (Tuesday and Friday) to a total of 10 doses at 15 cGy/fx. WR-2721 was given intravenously over 15 min beginning 30 min before irradiation. The escalation of WR-2721 was Level 1: 740 mg/m2 and Level 2: 910 mg/m2. The MTD of WR-2721 was that dose which produced predictable and reversible toxicity and would not interfere with patient well-being. Seven patients were entered onto the study, three at 740 mg/m2 and four at 910 mg/m2. Five patients had CLL and two patients small lymphocytic NHL. No patient had hypotension or nausea requiring reduction in dose level or even interruption of infusion of WR-2721. At 740 mg/m2 no grade 3 or 4 toxicities related to WR-2721 were observed, but two patients could not complete treatment because of TBI-induced prolonged thrombocytopenia following treatments 5 and 8. One patient completed all 10 treatments. At 910 mg/m2 of WR-2721, two patients requested removal from study because of malaise, one after 5 cycles and one after 7 cycles. One patient completed all 10 treatments.« less

Evidence-based Critical Evaluation of Glycemic Potential of Cynodon dactylon

PubMed Central

Singh, Santosh Kumar; Rai, Prashant Kumar; Jaiswal, Dolly

2008-01-01

The present study is an extension of our previous work carried out on Cynodon dactylon. This study deals with the critical evaluation of glycemic potential of ethanolic extract of defatted C. dactylon. The doses of 250, 500 and 750 mg kg−1 bw of the extract were administered orally to normal as well as Streptozotocin-induced diabetic rats to study its glycemic potential. The effect of repeated oral administration of the same doses of ethanolic extract was also studied on serum lipid profile of severely diabetic (SD) rats. The dose of 500 mg kg−1 bw was identified as the most effective dose as it lowered the blood glucose levels of normal by 42.12% and of diabetic by 43.42% during fasting blood glucose (FBG) and glucose tolerance test respectively. The SD rats were also treated daily with this identified dose of 500 mg kg−1 bw for 2 weeks and a significant reduction of 56.34% was observed in FBG level. Total cholesterol, low density lipoprotein and triglyceride levels were also decreased by 32.94, 64.06 and 48.46% respectively in SD rats whereas, cardioprotective high density lipoprotein increased by 16.45%. The reduced urine sugar level and increased body weight are additional advantages. These evidences clearly indicate that the ethanolic extract of defatted C. dactylon has high antidiabetic potential along with good hypolipidemic profile. PMID:18955211

Effect of dose rate on residual γ-H2AX levels and frequency of micronuclei in X-irradiated mouse lymphocytes.

PubMed

Turner, H C; Shuryak, I; Taveras, M; Bertucci, A; Perrier, J R; Chen, C; Elliston, C D; Johnson, G W; Smilenov, L B; Amundson, S A; Brenner, D J

2015-03-01

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

Toxicological profile of ultrapure 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180) in adult rats.

PubMed

Viluksela, Matti; Heikkinen, Päivi; van der Ven, Leo T M; Rendel, Filip; Roos, Robert; Esteban, Javier; Korkalainen, Merja; Lensu, Sanna; Miettinen, Hanna M; Savolainen, Kari; Sankari, Satu; Lilienthal, Hellmuth; Adamsson, Annika; Toppari, Jorma; Herlin, Maria; Finnilä, Mikko; Tuukkanen, Juha; Leslie, Heather A; Hamers, Timo; Hamscher, Gerd; Al-Anati, Lauy; Stenius, Ulla; Dervola, Kine-Susann; Bogen, Inger-Lise; Fonnum, Frode; Andersson, Patrik L; Schrenk, Dieter; Halldin, Krister; Håkansson, Helen

2014-01-01

PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

PubMed Central

Viluksela, Matti; Heikkinen, Päivi; van der Ven, Leo T. M.; Rendel, Filip; Roos, Robert; Esteban, Javier; Korkalainen, Merja; Lensu, Sanna; Miettinen, Hanna M.; Savolainen, Kari; Sankari, Satu; Lilienthal, Hellmuth; Adamsson, Annika; Toppari, Jorma; Herlin, Maria; Finnilä, Mikko; Tuukkanen, Juha; Leslie, Heather A.; Hamers, Timo; Hamscher, Gerd; Al-Anati, Lauy; Stenius, Ulla; Dervola, Kine-Susann; Bogen, Inger-Lise; Fonnum, Frode; Andersson, Patrik L.; Schrenk, Dieter; Halldin, Krister; Håkansson, Helen

2014-01-01

PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions. PMID:25137063

Combined reactor neutron beam and {sup 60}Co γ-ray radiation effects on CMOS APS image sensors

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Chen, Wei; Sheng, Jiangkun

The combined reactor neutron beam and {sup 60}Co γ-ray radiation effects on complementary metal-oxide semiconductor (CMOS) active pixel sensors (APS) have been discussed and some new experimental phenomena are presented. The samples are manufactured in the standard 0.35-μm CMOS technology. Two samples were first exposed to {sup 60}Co γ-rays up to the total ionizing dose (TID) level of 200 krad(Si) at the dose rates of 50.0 and 0.2 rad(Si)/s, and then exposed to neutron fluence up to 1 × 10{sup 11} n/cm{sup 2} (1-MeV equivalent neutron fluence). One sample was first exposed to neutron fluence up to 1 × 10{supmore » 11} n/cm{sup 2} (1-MeV equivalent neutron fluence), and then exposed to {sup 60}Co γ-rays up to the TID level of 200 krad(Si) at the dose rate of 0.2 rad(Si)/s. The mean dark signal (K{sub D}), the dark signal non-uniformity (DSNU), and the noise (V{sub N}) versus the total dose and neutron fluence has been investigated. The degradation mechanisms of CMOS APS image sensors have been analyzed, especially for the interaction induced by neutron displacement damage and TID damage.« less

Genetic effects in children exposed in prenatal period to ionizing radiation after the Chornobyl nuclear power plant accident.

PubMed

Stepanova, Ye I; Vdovenko, V Yu; Misharina, Zh A; Kolos, V I; Mischenko, L P

2016-12-01

To study the genetic effects in children exposed to radiation in utero as a result of the Chornobyl nuclear power plant accident accounting the total radiation doses and equivalent radiation doses to the red bone marrow. Incidence of minor developmental anomalies was studied in children exposed to radiation in utero (study group) and in the control group (1144 subjects surveyed in total). Cytogenetic tests using the method of differential G-banding of chromosomes were conducted in 60 children of both study and control groups (10-12-year-olds) and repeatedly in 39 adolescents (15-17-year-olds). A direct correlation was found between the number of minor developmental anomalies and fetal dose of radiation, and a reverse one with fetal gestational age at the time of radiation exposure. Incidence of chromosomal damage in somatic cells of 10-12-year-old children exposed prenatally was associated with radiation dose to the red bone marrow. The repeated testing has revealed that an increased level of chromosomal aberrations was preserved in a third of adolescents. The persons exposed to ionizing radiation at prenatal period should be attributed to the group of carcinogenic risk due to persisting increased levels of chromosome damage. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Water-soluble quercetin modulates the choleresis and bile lipid ratio in rats.

PubMed

Vovkun, Tatiana; Yanchuk, Petro; Shtanova, Lidiya; Veselskiy, Stanislav; Filimonova, Natalia; Shalamay, Anatoly; Vedmid, Volodymyr

2018-01-01

Water-soluble analogue of quercetin, corvitin is used in patients with myocardial infarction as blocker of 5-lipoxygenase. However, its effects on secretion, lipid content and physico-chemical properties of bile have not been understood yet. We investigated the effect of corvitin, applied in different doses, on the level of bile flow, the content of bile free and esterified cholesterol, phospholipids, triacylglycerols, and free fatty acids. In order to determine stability of the bile colloidal system, we examined the relationship between different lipid components. The rats were injected intraportally with a bolus of corvitin. At doses of 2.5, 5, and 10 mg/kg, the latter increased bile flow and concentration of total cholates, as well as free fatty acids. Corvitin (5 mg/kg) elevated phospholipids and cholesterol content, but at a dose of 10 mg/kg it increased the concentration of bile cholesterol esters and triacylglycerols. Corvitin applied at doses of 2.5 and 10 mg/kg increased total cholates/cholesterol ratio, but at a dose of 10 mg/kg, the drug reduced cholesterol / esterified cholesterol ratio. The results suggest that corvitin exerts choleretic effect and improves stability of bile colloidal system.

A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458)

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

Shaib, Walid L.; Hawk, Natalyn; Cassidy, Richard J.

Purpose: A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. Methods and Materials: A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV,more » and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Results: Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). Conclusion: The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.« less

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi;

A flux-based assessment of above and below ground biomass of Holm oak (Quercus ilex L.) seedlings after one season of exposure to high ozone concentrations

NASA Astrophysics Data System (ADS)

Gerosa, Giacomo; Fusaro, Lina; Monga, Robert; Finco, Angelo; Fares, Silvano; Manes, Fausto; Marzuoli, Riccardo

2015-07-01

Young plants of Holm oak (Quercus ilex) were exposed in non-limiting water conditions to four different levels of ozone (O3) concentrations in Open-Top Chambers during one growing season to evaluate biomass losses on roots, stems and leaves in relation to O3 exposure (AOT40) and phytotoxical ozone dose (POD1) absorbed. The exposure-effect and dose-effect relationships for the total biomass were statistically significant and indicated a reduction of 4% and 5.2% of the total biomass for each increase step of 10000 ppb h of AOT40 and 10 mmol m-2 of POD1, respectively. The results indicate a critical level for Holm oak protection of 7 mmol m-2 of POD1, which corresponds to 4% of total biomass reduction. The linear regressions based on the POD1 were significant for roots and stem biomass losses, but not significant for leaf biomass. The biomass loss rate at increasing POD1 was higher for roots than for stems and leaves, suggesting that stem growth under high levels of O3 is less affected than root growth. Because of the scarcity of data from the Mediterranean area, these results can be relevant for the O3 risk assessment models and for the definition of new O3 critical levels for forests in Europe.

Outpatient radioiodine therapy for thyroid cancer: a safe nuclear medicine procedure.

PubMed

Willegaignon, José; Sapienza, Marcelo; Ono, Carla; Watanabe, Tomoco; Guimarães, Maria Inês; Gutterres, Ricardo; Marechal, Maria Helena; Buchpiguel, Carlos

2011-06-01

To evaluate the dosimetric effect of outpatient radioiodine therapy for thyroid cancer in members of a patient's family and their living environment, when using iodine-131 doses reaching 7.4 GBq. The following parameters were thus defined: (a) whole-body radiation doses to caregivers, (b) the production of contaminated solid waste, and (c) radiation potential and surface contamination within patients' living quarters. In total, 100 patients were treated on an outpatient basis, taking into consideration their acceptable living conditions, interests, and willingness to comply with medical and radiation safety guidelines. Both the caregivers and the radiation dose potentiality inside patients' residences were monitored by using thermoluminescent dosimeters. Surface contamination and contaminated solid wastes were identified and measured with a Geiger-Müller detector. A total of 90 monitored individuals received a mean dose of 0.27 (±0.28) mSv, and the maximum dose registered was 1.6 mSv. The mean value for the potential dose within all living quarters was 0.31 (±0.34) mSv, and the mean value per monitored surface was 5.58 Bq/cm(2) for all the 1659 points measured. The overall production of contaminated solid wastes was at a low level, being about 3 times less than the exemption level indicated by the International Atomic Energy Agency. This study indicates that the treatment of thyroid cancer by applying radioiodine activities up to 7.4 GBq, on an outpatient basis, is a safe procedure, especially when supervised by qualified professionals. This alternative therapy should be a topic for careful discussion considering the high potential for reducing costs in healthcare and improving patient acceptance.

High-dose anti-histamine use and risk factors in children with urticaria.

PubMed

Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

2016-12-01

The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p<0.0001). There was no difference between the two groups in terms of blood eosinophil and basophil counts, and serum total IgE levels (p>0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=-0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03-1.15]) and basopenia (OR: 6.77; CI 95%: [2.01-22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. The requirement of high-dose H1-antihistamines was higher with children's increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines.

Comparison of the effects of three different Baccaurea angulata whole fruit juice doses on plasma, aorta and liver MDA levels, antioxidant enzymes and total antioxidant capacity.

PubMed

Ibrahim, Muhammad; Mikail, Maryam Abimbola; Ahmed, Idris Adewale; Hazali, Norazlanshah; Abdul Rasad, Mohammad Syaiful Bahari; Abdul Ghani, Radiah; Hashim, Ridzwan; Arief, Solachuddin Jahuari; Md Isa, Muhammad Lokman; Draman, Samsul

2017-05-17

Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice showed that it possesses antioxidant properties. Therefore, further work is needed to confirm the efficacy and proper dosage of B. angulata as a potential natural antioxidant. The present study was thus carried out to compare the effects of three different B. angulata whole fruit (WF) juice doses administered at nutritional doses of 0.50, 1.00 and 1.50 ml/kg/day on plasma, aorta and liver malondialdehyde (MDA) levels, antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) as well as total antioxidant capacity in rabbits fed high-cholesterol diet. Thirty-five male rabbits of New Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50 ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00 ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50 ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1 was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was fed standard pellet and 1.00 ml/kg/day B. angulata WF juice. The three doses reduced the formation of MDA and enhanced the expression of endogenous antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as the most potent. Higher doses of B. angulata juice exerted better antioxidant activity.

Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial.

PubMed

Cengiz, Pelin; Gokcinar, Derya; Karabeyoglu, Isil; Topcu, Hulya; Cicek, Gizem Selen; Gogus, Nermin

2014-05-01

To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. A randomized, double-blind comparative study. Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6 μg/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects.

TU-CD-304-04: Scanning Field Total Body Irradiation Using Dynamic Arc with Variable Dose Rate and Gantry Speed

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

Yi, B; Xu, H; Mutaf, Y

2015-06-15

Purpose: Enable a scanning field total body irradiation (TBI) technique, using dynamic arcs, which is biologically equivalent to a moving couch TBI. Methods: Patient is treated slightly above the floor and the treatment field scans across the patient by a moving gantry. MLC positions change during gantry motion to keep same field opening at the level of the treatment plane (170 cm). This is done to mimic the same geometry as the moving couch TBI technique which has been used in our institution for over 10 years. The dose rate and the gantry speed are determined considering a constant speedmore » of the moving field, variations in SSD and slanted depths resulting from oblique gantry angles. An Eclipse (Varian) planning system is commissioned to accommodate the extended SSD. The dosimetric foundations of the technique have been thoroughly investigated using phantom measurements. Results: Dose uniformity better than 2% across 180 cm length at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Treatment range can be extended by increasing gantry range. No device such as a gravity-oriented compensator is needed to achieve a uniform dose. It is feasible to modify the dose distribution by adjusting the dose rate at each gantry angle to compensate for body thickness differences. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 100 MU/min. Conclusion: This novel yet transportable moving field technique enables TBI treatment in a small treatment room with less program development preparation than other techniques. Treatment length can be extended per need, and. MLC-based thickness compensation and partial lung blocking are also possible.« less

Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

PubMed

Santarmaki, Valentini; Kourkoutas, Yiannis; Zoumpopoulou, Georgia; Mavrogonatou, Eleni; Kiourtzidis, Mikis; Chorianopoulos, Nikos; Tassou, Chrysoula; Tsakalidou, Effie; Simopoulos, Constantinos; Ypsilantis, Petros

2017-09-01

Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

Effect of fat on serum 25-hydroxyvitamin D levels after a single oral dose of vitamin D in young healthy adults: a double-blind randomized placebo-controlled study.

PubMed

Raimundo, Fabiana Viegas; Lang, Maria Augusta Britto; Scopel, Luciano; Marcondes, Natália Aydos; Araújo, Mirna Griselda Anocibar; Faulhaber, Gustavo Adolpho Moreira; Furlanetto, Tania Weber

2015-04-01

This double-blind placebo-controlled trial evaluated serum 25-hydroxyvitamin D [25(OH)D] levels after the oral intake of a single dose of cholecalciferol during one of the three meals, containing different amounts of fat or placebo. Sixty-four healthy medical residents or students of a university hospital in Porto Alegre, latitude 30° S, Brazil, were divided into four groups. Three groups received a single 50,000 IU oral dose of cholecalciferol during a meal containing 0 g (Group 1), 15 g (Group 2) or 30 g (Group 3) of fat, and one group received placebo (Group 4), according to randomization. Serum 25(OH)D, parathyroid hormone, total calcium, albumin, magnesium, and creatinine levels, and urinary calcium, magnesium, and creatinine levels were measured at baseline and after 14 days. Baseline mean serum 25(OH)D levels were low in all groups. Vitamin D given during breakfast increased the mean change of serum 25(OH)D levels, when compared to placebo. Furthermore, the intake of fat with vitamin D increased the mean change of serum 25(OH)D levels. A single oral dose of vitamin D given with food increased mean serum 25(OH)D levels, after 2 weeks, and the mean increase was larger, when the meal had at least 15 g of fat. These findings can have important implications to oral vitamin D supplementation.

Inhalation and Ingestion Intakes with Associated Dose Estimates for Level II and Level III Personnel Using Capstone Study Data

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

Szrom, Fran; Falo, Gerald A.; Lodde, Gordon M.

2009-03-01

Depleted uranium (DU) intake rates and subsequent dose rates were estimated for personnel entering armored combat vehicles perforated with DU penetrators (level II and level III personnel) using data generated during the Capstone Depleted Uranium (DU) Aerosol Study. Inhalation intake rates and associated dose rates were estimated from cascade impactors worn by sample recovery personnel and from cascade impactors that served as area monitors. Ingestion intake rates and associated dose rates were estimated from cotton gloves worn by sample recovery personnel and from wipe test samples from the interior of vehicles perforated with large caliber DU munitions. The mean DUmore » inhalation intake rate for level II personnel ranged from 0.447 mg h-1 based on breathing zone monitor data (in and around a perforated vehicle) to 14.5 mg h-1 based on area monitor data (in a perforated vehicle). The mean DU ingestion intake rate for level II ranged from 4.8 mg h-1 to 38.9 mg h-1 based on the wipe test data including surface to glove transfer factors derived from the Capstone data. Based on glove contamination data, the mean DU ingestion intake rates for level II and level III personnel were 10.6 mg h-1 was and 1.78 mg h-1, respectively. Effective dose rates and peak kidney uranium concentration rates were calculated based on the intake rates. The peak kidney uranium concentration rate cannot be multiplied by the total exposure duration when multiple intakes occur because uranium will clear from the kidney between the exposures.« less

[Features of influence adenosine, AMP and hyperadrenalinemiya on the immune status, metabolic enzymes of purine nucleotides and the antioxidant defense system].

PubMed

Tapbergenov, S O; Sovetov, B S; Tapbergenov, A T

2016-11-01

Administration of a large dose of adrenaline (4 mg/kg 60 min before analysis) increased blood levels of total leukocytes, lymphocytes, decreased T-cell suppressors, leukocyte migration inhibition reaction (LMIR) and NBT test, but increased the level of conjugated dienes (CD). Administration of AMPand adenosine increased levels of total leukocytes, lymphocytes, T- lymphocytes, T-helpers, decreased the level of malondialdehyde (MDA), LMIR, and T-cell suppressors. Sympathetic hyperactivation induced by administration of a large dose of adrenaline (4 mg/kg 60 min before analysis) was accompanied by an increase in heart and liver activities of glutathione peroxidase (GPx), catalase, AMP deaminase (AMPD), and adenosine deaminase (AD). Administration of AMP or adenosine caused a decrease in activities of glutathione reductase (GR), GPx, catalase, a decrease in the MDA level and an increase in activities of AMPD and AD in the heart. In the liver AMP and adenosine also caused a decrease in activities of glutathione reductase (GR), GPx, a decrease in the MDA level and an increase in activities of AMPD and AD. The data obtained suggest that administration of adrenaline, AMP, and adenosine influences activity of enzymes involved in purine nucleotide metabolism. However, in contrast to adrenaline, administration of AMP or adenosine does not provoke stress reaction.

Chinese Data of Efficacy of Low- and High-Dose Iodine-131 for the Ablation of Thyroid Remnant.

PubMed

Ma, Chao; Feng, Fang; Wang, Shaoyan; Fu, Hongliang; Wu, Shuqi; Ye, Zhiyi; Chen, Suyun; Wang, Hui

2017-06-01

Chinese data on the efficacy of low- and high-dose radioiodine for thyroid remnant are still absent. The aim of the study was to investigate whether a low dose of radioiodine is as effective as a high dose for remnant ablation in Chinese patients. Patients presenting for radioiodine ablation in the authors' department were included. Inclusion criteria were aged ≥16 years, total or near-total thyroidectomy, tumor-node-metastasis (TNM) stage of pT1-3, any N stage, and M0. All patients were randomly allocated to either the high-dose group of 3700 MBq or the low-dose group of 1850 MBq for remnant ablation. The response to treatment was defined as successful or unsuccessful after a six- to nine-month interval. Ablation was considered to be successful if patients fulfilled the following criteria: no tracer uptake in the thyroid bed on diagnosis whole-body scanning and a negative level of serum thyroglobulin. There were 327 patients enrolled between January 2013 and December 2014. More than 95% had papillary thyroid cancer. Data could be analyzed for 278 cases (M age  = 44 years; 71.6% women), 155 in the low-dose group and 123 in the high-dose group. The rate of initial successful ablation was 84.2% in all patients, 82.6% in the low-dose group, and 86.2% in the high-dose group. There was no difference between the two groups (p = 0.509). In Chinese patients with differentiated thyroid carcinoma, the low dose of 1850 MBq radioiodine activity is as effective as a high dose of 3700 MBq for thyroid remnant ablation.

Organ Dose-Rate Calculations for Small Mammals at Maralinga, the Nevada Test Site, Hanford and Fukushima: A Comparison of Ellipsoidal and Voxelized Dosimetric Methodologies.

PubMed

Caffrey, Emily A; Johansen, Mathew P; Higley, Kathryn A

2015-10-01

Radiological dosimetry for nonhuman biota typically relies on calculations that utilize the Monte Carlo simulations of simple, ellipsoidal geometries with internal radioactivity distributed homogeneously throughout. In this manner it is quick and easy to estimate whole-body dose rates to biota. Voxel models are detailed anatomical phantoms that were first used for calculating radiation dose to humans, which are now being extended to nonhuman biota dose calculations. However, if simple ellipsoidal models provide conservative dose-rate estimates, then the additional labor involved in creating voxel models may be unnecessary for most scenarios. Here we show that the ellipsoidal method provides conservative estimates of organ dose rates to small mammals. Organ dose rates were calculated for environmental source terms from Maralinga, the Nevada Test Site, Hanford and Fukushima using both the ellipsoidal and voxel techniques, and in all cases the ellipsoidal method yielded more conservative dose rates by factors of 1.2-1.4 for photons and 5.3 for beta particles. Dose rates for alpha-emitting radionuclides are identical for each method as full energy absorption in source tissue is assumed. The voxel procedure includes contributions to dose from organ-to-organ irradiation (shown here to comprise 2-50% of total dose from photons and 0-93% of total dose from beta particles) that is not specifically quantified in the ellipsoidal approach. Overall, the voxel models provide robust dosimetry for the nonhuman mammals considered in this study, and though the level of detail is likely extraneous to demonstrating regulatory compliance today, voxel models may nevertheless be advantageous in resolving ongoing questions regarding the effects of ionizing radiation on wildlife.

Comparison of different approaches of estimating effective dose from reported exposure data in 3D imaging with interventional fluoroscopy systems

NASA Astrophysics Data System (ADS)

Svalkvist, Angelica; Hansson, Jonny; Bâth, Magnus

2014-03-01

Three-dimensional (3D) imaging with interventional fluoroscopy systems is today a common examination. The examination includes acquisition of two-dimensional projection images, used to reconstruct section images of the patient. The aim of the present study was to investigate the difference in resulting effective dose obtained using different levels of complexity in calculations of effective doses from these examinations. In the study the Siemens Artis Zeego interventional fluoroscopy system (Siemens Medical Solutions, Erlangen, Germany) was used. Images of anthropomorphic chest and pelvis phantoms were acquired. The exposure values obtained were used to calculate the resulting effective doses from the examinations, using the computer software PCXMC (STUK, Helsinki, Finland). The dose calculations were performed using three different methods: 1. using individual exposure values for each projection image, 2. using the mean tube voltage and the total DAP value, evenly distributed over the projection images, and 3. using the mean kV and the total DAP value, evenly distributed over smaller selection of projection images. The results revealed that the difference in resulting effective dose between the first two methods was smaller than 5%. When only a selection of projection images were used in the dose calculations the difference increased to over 10%. Given the uncertainties associated with the effective dose concept, the results indicate that dose calculations based on average exposure values distributed over a smaller selection of projection angles can provide reasonably accurate estimations of the radiation doses from 3D imaging using interventional fluoroscopy systems.

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

Heijst, T C F van; Hoekstra, N; Philippens, M E P

Purpose: The Utrecht MRI-linac (MRL) design enables new MR-guided radiotherapy (RT) approaches. This is a feasibility study for a single-fraction high dose (boost) to individual lymph nodes (LNs) in breast-cancer patients, after breast-conserving surgery (BCS) and hypofractionated whole-breast irradiation (WBI) with conventional axillary RT (AxRT). Methods: After written informed consent, 5 breast-cancer patients (cT1-3N0) were enrolled (NL500460.041.14 trial) and underwent 1.5T MRI in supine RT position, after BCS. Axillary levels, based on ESTRO guidelines, and organs-at-risk (OARs) – including lungs, chest wall, plexus and neurovascular bundle (NVB) – were delineated. Pseudo-CT scans (pCTs) were generated by HU bulk-assignment of water,more » lung, and air. With Monaco treatment-planning software (TPS Elekta), VMAT plans were generated for simultaneous WBI and AxRT, prescribing 16×2.66=42.56Gy (V95%>99% V107%<2cc). Two scenarios were considered: AxRT of levels I–II; AxRT of levels I–IV, depending on boost location. Per patient, 4 LNs with varying axillary locations were selected, delineated, and expanded to PTV with 2-mm margin. Using dedicated MRL TPS, accounting for magnetic-field effects, an IMRT 1×8.5Gy boost was simulated for each LN, to achieve a total target dose of 66Gy EQD2 (α/β=3.5Gy). WBI/ART doses and boost doses were added, and evaluated in EQD2. Results: For all scenarios, 1×8.5Gy boosts could be simulated within clinical constraints for a 66Gy total dose, in addition to WBI/AxRT. LN target coverage was excellent (V95%>95%, mean >8.5Gy). Additional dose to OARs was limited. Conclusion: Our study explored the concept of LN boosting using on-line MRI guidance. It is feasible to boost individual axillary LNs – with 2-mm margin – with an additional 1×8.5Gy, in all axillary levels, within clinical constraints. This may lead to more personalized RT approaches for patients with involved LNs and may reduce RT-induced toxicity, or the need for axillary surgery. Other LN boost strategies, including dose escalation, are under investigation.« less

Evaluation of Myrtus communis Linn. berries (common myrtle) in experimental ulcer models in rats.

PubMed

Sumbul, Sabiha; Ahmad, Mohd Aftab; Asif, Mohd; Saud, Ibne; Akhtar, Mohd

2010-11-01

The present study was conducted to investigate the protective effect of the dried berries of Myrtus communis L. in gastric ulcer against ethanol, indomethacin and pyloric ligation induced models in Wistar rats. Two doses of aqueous extracts of M. communis (AE( 1) and AE(2)) at the dose 105 and 175 mg/kg, respectively, and methanolic extracts (ME(1) and ME(2)) at the dose of 93 and 154 mg/kg, respectively, were administered orally to animals prior to the exposure of ulcerogens. The parameters taken to assess anti-ulcer activity were ulcer index, gastric juice volume, gastric pH, total acidity, gastric wall mucus and histopathological studies. Oral administration of AE(1) and AE(2) significantly reduced the ulcer index in all models of ulcers. Low dose of aqueous extract and high dose of methanolic extract of M. communis exhibited more significant effect in comparison to omeprazole (standard drug) in ethanol-induced ulcer model. Both the doses of aqueous and methanolic extracts also reduced the gastric juice volume, total acidity and increased the gastric pH and gastric wall mucus content in all the models of ulcers used in the present study. Histopathological examinations of gastric tissues of rats treated with the aqueous and methanolic extracts in indomethacin-induced ulcer exhibited significant ulcer-protective effect at both the dose levels.

Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Comparison of two dosage schedules of choline magnesium trisalicylate.

PubMed

Cassell, S; Furst, D; Dromgoole, S; Paulus, H

1979-04-01

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a ddecrease of 1 mg/dl in mean minimum concentration.

Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes.

PubMed

Kulkarni, Yogesh A; Garud, Mayuresh S

2016-10-01

Among various metabolic disorders, diabetes mellitus is one of the most common disorder. Present study was designed to evaluate the effectiveness of aqueous extract of Bauhinia variegata leaves (AE) in animal models of type I and type II diabetes. Type I diabetes was induced by streptozotocin at the dose of 55mg/kg (i.p.) in male Sprague Dawley rats while type II diabetes was induced by high fat diet and streptozotocin at the dose of 35mg/kg (i.p.). Diabetic animals were treated with AE at the dose of 250, 500 and 1000mg/kg. Glipizide (5mg/kg) was used as standard treatment drug. Treatment was given for 28days. Parameters evaluated were body weight, plasma glucose, cholesterol, triglyceride, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total proteins, albumin, creatinine and bun urea nitrogen. In type II diabetes, high density lipoprotein levels in plasma and plasma insulin level were also evaluated. Histopathological study of pancreases were carried out in type I study. AE showed significant decrease in plasma glucose significantly. AE was also found to decrease cholesterol, triglyceride, creatinine and blood urea nitrogen level in both types of diabetes. AE did not show any significant effect on plasma levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase. AE was found to increase the albumin and total protein levels. Histopathological study showed that AE decreases the necrotic changes in the pancreatic tissue. Aqueous extract of B. variegata leaves was found effective in treatment of both type I and type II diabetes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway.

PubMed

Zhao, Jing; Liu, Ge-Li; Wei, Ying; Jiang, Li-Hong; Bao, Peng-Li; Yang, Qing-Yan

2016-09-01

The aim of the present study was to investigate the effect of testosterone on glucolipid metabolism and vascular injury in male rats, and examine the underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were divided into a control group (n=10), high-fat-diet + castration group (n=10), high‑fat‑diet + castration + low dose testosterone group (n=10), and high-fat-diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin staining was performed to evaluate the morphology of the thoracic aortic tissues. Immunohistochemical staining was used to detect biomarkers of the phosphoinositide 3‑kinase (PI3K) signaling pathway. The mRNA and protein expression levels of PI3K, AKT, insulin receptor substrate‑1 (IRS‑1), glucose transporter type 4 (GLUT‑4), nuclear factor (NF)‑κB and tumor necrosis factor (TNF)‑α in the aortas were determined using quantitative polymerase chain reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues was detected using a TUNEL assay. Castration induced apoptosis in the animals fed a high‑fat‑diet, whereas low dose testosterone replacement ameliorated the apoptosis in the aorta. However, the levels of apoptosis was more severe following high‑dose testosterone treatment. Low‑dose testosterone induced upregulation in the levels of IRS‑1, AKT, GLUT‑4 protein, NF‑κB, TNF‑α and PI3K, compared with those in the animals fed a high‑fat diet following castration. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT, GLUT‑4, NF‑κB, TNF‑α and PI3K. Compared with the rats in the high‑fat diet + castration group, a low dose of testosterone induced upregulation in the mRNA levels of IRS‑1, AKT and GLUT‑4, and downregulation of the mRNA levels of NF‑κB, TNF‑α and PI3K. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT and GLUT‑4, and marked increases in the mRNA levels of NF‑κB, TNF‑α and PI3K, compared with the low dose group. Castration induced marked disorders of glucolipid metabolism and vascular injuries in the pubescent male rats. Low‑dose testosterone treatment was found to ameliorate the vascular damage caused by castration via the PI3K/AKT signaling pathway.

Analysis of buprenorphine/naloxone dosing impact on treatment duration, resource use and costs in the treatment of opioid-dependent adults: a retrospective study of US public and private health care claims.

PubMed

Khemiri, Amine; Kharitonova, Elizaveta; Zah, Vladimir; Ruby, Jane; Toumi, Mondher

2014-09-01

The buprenorphine/naloxone combination is used to treat the chronic relapsing disorder of opioid dependence. Adequate dosing levels are important to control cravings, prevent withdrawal syndrome, and maintain patients in treatment. The objective of this study was to estimate the impact of dosing on treatment persistence, resource utilization, and total direct health care costs. A retrospective cohort analysis was performed using administrative claims extracted from the MarketScan and Clinformatics databases from January 2007 to June and November 2012. Patients initiating treatment with buprenorphine/naloxone were classified into 2 groups based on the prescribed average dose over the entire treatment period and matched by multiple criteria. The threshold for differentiating the dosing groups was set at 15 and 15.7 mg/day for publicly and privately insured patients, respectively. Resource utilization and related costs were calculated over the 12-month period after the treatment initiation. Patient characteristics at baseline were considerably different between the privately and publicly insured patients. Publicly insured patients were slightly younger (33.1 vs 34.3 years old for privately insured) and had a higher prevalence of mental disorders (70.9% vs 64.9%). In both groups, patients treated with higher doses (> 15 mg and > 15.7 mg per day for publicly and privately insured patients, respectively) had lower risk of discontinuation (public: 11% lower; private: 9% lower) and lower probability of a psychiatric hospitalization than patients treated with lower doses (public: 17% lower; private: 41% lower). Total costs were comparable between the 2 groups (public: $14 600; private: $21 000) despite the expected higher cost of pharmacy in the higher-dose group. Treatment with higher doses of buprenorphine/naloxone was associated with a longer time to treatment discontinuation, less resource use, and lower total medical costs despite higher pharmacy acquisition cost.

CERISE, a French radioprotection code, to assess the radiological impact and acceptance criteria of installations for material handling, and recycling or disposal of very low-level radioactive waste

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

Santucci, P.; Guetat, P.

1993-12-31

This document describes the code CERISE, Code d`Evaluations Radiologiques Individuelles pour des Situations en Enterprise et dans l`Environnement. This code has been developed in the frame of European studies to establish acceptance criteria of very low-level radioactive waste and materials. This code is written in Fortran and runs on PC. It calculates doses received by the different pathways: external exposure, ingestion, inhalation and skin contamination. Twenty basic scenarios are already elaborated, which have been determined from previous studies. Calculations establish the relation between surface, specific and/or total activities, and doses. Results can be expressed as doses for an average activitymore » unit, or as average activity limits for a set of reference doses (defined for each scenario analyzed). In this last case, the minimal activity values and the corresponding limiting scenarios, are selected and summarized in a final table.« less

First-in-man-proof of concept study with molidustat: a novel selective oral HIF-prolyl hydroxylase inhibitor for the treatment of renal anaemia.

PubMed

Böttcher, M; Lentini, S; Arens, E R; Kaiser, A; van der Mey, D; Thuss, U; Kubitza, D; Wensing, G

2018-07-01

Insufficient erythropoietin (EPO) synthesis is a relevant cause of renal anaemia in patients with chronic kidney disease. Molidustat, a selective hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, increases endogenous EPO levels dose dependently in preclinical models. We examined the pharmacokinetics, safety, tolerability and effect on EPO levels of single oral doses of molidustat in healthy male volunteers. This was a single-centre, randomized, single-blind, placebo-controlled, group-comparison, dose-escalation study. Molidustat was administered at doses of 5, 12.5, 25, 37.5 or 50 mg as a polyethylene glycol-based solution. In total, 45 volunteers received molidustat and 14 received placebo. Molidustat was absorbed rapidly, and the mean maximum plasma concentration and area under the concentration-time curve increased dose dependently. The mean terminal half-life was 4.64-10.40 h. A significant increase in endogenous EPO was observed following single oral doses of molidustat of 12.5 mg and above. Geometric mean peak EPO levels were 14.8 IU l -1 (90% confidence interval 13.0, 16.9) for volunteers who received placebo and 39.8 IU l -1 (90% confidence interval: 29.4, 53.8) for those who received molidustat 50 mg. The time course of EPO levels resembled the normal diurnal variation in EPO. Maximum EPO levels were observed approximately 12 h postdose and returned to baseline after approximately 24-48 h. All doses of molidustat were well tolerated and there were no significant changes in vital signs or laboratory safety parameters. Oral administration of molidustat to healthy volunteers elicited a dose-dependent increase in endogenous EPO. These results support the ongoing development of molidustat as a potential new treatment for patients with renal anaemia. © 2018 The British Pharmacological Society.

Will X-ray Safety Glasses Become Mandatory for Radiological Vascular Interventions?

PubMed

Thomas, Rohit Philip; Grau, Mathias; Eldergash, Osama; Kowald, Tobias; Schnabel, Johannes; Szczechowicz, Marcin; Chavan, Ajay

2018-07-01

The annual permissible radiation ocular lens dose has been reduced to 20 millisieverts (mSv) in the current European directive 2013/59/Euratom. The aim of this study was to evaluate the personal radiation dose for vascular interventions with special focus on ocular lens dose. From May 2016 to October 2016, the personal radiation doses of two interventionists and four technicians were prospectively recorded during 206 vascular interventions. The position of personnel, intervention type and fluoroscopy time were recorded. Parameters evaluated were total body dose measured by film dosimeter, hand dose measured by ring thermoluminescent dosimeter (TLD) and ocular lens dose measured by TLD placed in front of the safety glasses. Linear regression analysis was used to estimate the dose at 2 and 5 years. The ocular lens dose, hand and total body dose of the two interventionists were 11/5, 56/47 and 0.6 mSv each, respectively. The estimated 5-year ocular dose was 113.08 mSv (95% CI 38.2-187.97)/40.95 (95% CI 16.9-64.7). Similarly, hand dose was 608.4 mSv (95% CI 442.78-774.38)/514.47 (95% CI 329.83-699.10) and body dose 6.07 mSv (95% CI 4.70-8.22)/5.12 (95% CI 3.65-6.59), respectively. Amongst four technicians, only the first assistant showed recordings of 0.3 mSv body dose, 2 mSv ocular lens dose and 5 mSv hand dose. The yearly ocular lens dose, particularly for interventionists dealing with complex interventions, could cross the permitted yearly limit set by the new Euratom directive. Therefore, X-ray safety glasses would become mandatory for complex radiological vascular interventions. Level III, non-randomized controlled cohort/follow-up study.

Systemic levels of local anaesthetic after intra-peritoneal application--a systematic review.

PubMed

Kahokehr, A; Sammour, T; Vather, R; Taylor, M; Stapelberg, F; Hill, A G

2010-07-01

There is a lack of cohesive reports on the systemic levels of local anaesthetic after intraperitoneal application. A comprehensive systematic review with no language restriction was conducted. Eighteen suitable articles were identified. Data were compiled and presented according to local anaesthetic agent. Intraperitoneal local anaesthetic has been studied in many different procedures, including open and laparoscopic surgery. A total of 415 patients were included for analysis. There were no cases of clinical toxicity. There were 11 (2.7%) cases with a systemic level above or close to a safe threshold (as determined by the report authors) in three trials utilising intraperitoneal local anaesthetic after laparoscopic cholecystectomy. Intraperitoneal lignocaine doses varied from 100 to 1000 mg, mean Cmax ranged from 1.01 to 4.32 microg/ml and mean Tmax ranged from 15 to 40 minutes. Intraperitoneal bupivacaine doses varied from 50 to 150 mg (weight based doses also reported), mean Cmax ranged from 0.29 to 1.14 microg/ml and mean Tmax ranged from 15 to 60 minutes. Intraperitoneal ropivacaine doses varied from 100 to 300 mg, mean Cmax ranged from 0.66 to 3.76 microg/ml and mean Tmax ranged from 15 to 35 minutes. The addition of adrenaline to intraperitoneal local anaesthetic almost halves systemic levels and prolongs Tmax. Intraperitoneal local anaesthetic results in detectable systemic levels in the perioperative setting. Despite a lack of clinical toxicity, careful attention to dose is still required to prevent potential systemic toxic levels. Clinicians should also consider the addition of adrenaline to intraperitoneal local anaesthetic solutions to further add to the systemic safety profile.

Influence of gamma-irradiation and maize lipids on the production of aflatoxin B1 by Aspergillus flavus.

PubMed

Aziz, Nagy H; el-Zeany, Samia A; Moussa, Lotfy A A

2002-10-01

The effect of gamma-irradiation and maize lipids on aflatoxin B1 production by Aspergillus flavus artificially inoculated into sterilized maize at reduced water activity (aw 0.84) was investigated. By increasing the irradiation doses the total viable population of A. flavus decreased and the fungus was completely inhibited at 3.0 kGy. The amounts of aflatoxin B1 were enhanced at irradiation dose levels 1.0 and 1.5 kGy in both full-fat maize (FM) and defatted maize (DM) media and no aflatoxin B1 production at 3.0 kGy gamma-irradiation over 45 days of storage was observed. The level in free lipids of FM decreased gradually, whereas free fatty acid values and fungal lipase activity increased markedly by increasing the storage periods. The free fatty acid values decreased by increasing the irradiation dose levels and there was a significant enhancement of fungal lipase activity at doses of 1.0 and 1.50 kGy. The ability of A. flavus to grow at aw 0.84 and produce aflatoxin B1 is related to the lipid composition of maize. The enhancement of aflatoxin B1 at low doses was correlated to the enhancement of fungal lipase activity.

Association Between Media Dose, Ad Tagging, and Changes in Web Traffic for a National Tobacco Education Campaign: A Market-Level Longitudinal Study

PubMed Central

Davis, Kevin C; Patel, Deesha; Rodes, Robert; Beistle, Diane

2016-01-01

Background In 2012, the US Centers for Disease Control and Prevention (CDC) launched Tips From Former Smokers (Tips), the first federally funded national tobacco education campaign. In 2013, a follow-up Tips campaign aired on national cable television networks, radio, and other channels, with supporting digital advertising to drive traffic to the Tips campaign website. Objective The objective of this study was to use geographic and temporal variability in 2013 Tips campaign television media doses and ad tagging to evaluate changes in traffic to the campaign website in response to specific doses of campaign media. Methods Linear regression models were used to estimate the dose-response relationship between weekly market-level television gross rating points (GRPs) and weekly Web traffic to the Tips campaign website. This relationship was measured using unique visitors, total visits, and page views as outcomes. Ad GRP effects were estimated separately for ads tagged with the Tips campaign website URL and 1-800-QUIT-NOW. Results In the average media market, an increase of 100 television GRPs per week for ads tagged with the Tips campaign website URL was associated with an increase of 650 unique visitors (P<.001), 769 total visits (P<.001), and 1255 total page views (P<.001) per week. The associations between GRPs for ads tagged with 1-800-QUIT-NOW and each Web traffic measure were also statistically significant (P<.001), but smaller in magnitude. Conclusions Based on these findings, we estimate that the 16-week 2013 Tips television campaign generated approximately 660,000 unique visitors, 900,000 total visits, and 1,390,000 page views for the Tips campaign website. These findings can help campaign planners forecast the likely impact of targeted advertising efforts on consumers’ use of campaign-specific websites. PMID:26887959

Changes in biochemical processes in cerebellar granule cells of mice exposed to methylmercury.

PubMed

Bellum, Sairam; Bawa, Bhupinder; Thuett, Kerry A; Stoica, Gheorghe; Abbott, Louise C

2007-01-01

At postnatal day 34, male and female C57BL/6J mice were exposed orally once a day to a total of five doses totaling 1.0 or 5.0 mg/kg of methylmercuric chloride or sterile deionized water in moistened rodent chow. Eleven days after the last dose cerebellar granule cells were acutely isolated to measure reactive oxygen species (ROS) levels and mitochondrial membrane potential using CM-H(2)DCFDA and TMRM dyes, respectively. For visualizing intracellular calcium ion distribution using transmission electron microscopy, mice were perfused 11 days after the last dose of methylmercury (MeHg) using the oxalate-pyroantimonate method. Cytosolic and mitochondrial protein fractions from acutely isolated granule cells were analyzed for cytochrome c content using Western blot analysis. Histochemistry (Fluoro-Jade dye) and immunohistochemistry (activated caspase 3) was performed on frozen serial cerebellar sections to label granule cell death and activation of caspase 3, respectively. Granule cells isolated from MeHg-treated mice showed elevated ROS levels and decreased mitochondrial membrane potential when compared to granule cells from control mice. Electron photomicrographs of MeHg-treated granule cells showed altered intracellular calcium ion homeostasis ([Ca(2+)](i)) when compared to control granule cells. However, in spite of these subcellular changes and moderate relocalization of cytochrome c into the cytosol, the concentrations of MeHg used in this study did not produce significant neuronal cell death/apoptosis at the time point examined, as evidenced by Fluoro-Jade and activated caspase 3 immunostaining, respectively. These results demonstrate that short-term in vivo exposure to total doses of 1.0 and 5.0 mg/kg MeHg through the most common exposure route (oral) can result in significant subcellular changes that are not accompanied by overt neuronal cell death.

Comparison of Propofol, Propofol-Remifentanil, and Propofol-Fentanyl Administrations with Each Other Used for the Sedation of Patients to Undergo ERCP

PubMed Central

Haytural, Candan; Aydınlı, Bahar; Demir, Berna; Bozkurt, Elif; Parlak, Erkan; Dişibeyaz, Selçuk; Saraç, Ahmet; Özgök, Ayşegül; Kazancı, Dilek

2015-01-01

Introduction. Using single anesthetic agent in endoscopic retrograde cholangiopancreatography (ERCP) may lead to inadequate analgesia and sedation. To achieve the adequate analgesia and sedation the single anesthetic agent doses must be increased which causes undesirable side effects. For avoiding high doses of single anesthetic agent nowadays combination with sedative agents is mostly a choice for analgesia and sedation for ERCP. Aim. The aim of this study is to investigate the effects of propofol alone, propofol + remifentanil, and propofol + fentanyl combinations on the total dose of propofol to be administered during ERCP and on the pain scores after the process. Materials and Method. This randomized study was performed with 90 patients (ASA I-II-III) ranging between 18 and 70 years of age who underwent sedation/analgesia for elective ERCP. The patients were administered only propofol (1.5 mg/kg) in Group Ι, remifentanil (0.05 μg/kg) + propofol (1.5 mg/kg) combination in Group II, and fentanyl (1 μg/kg) + propofol (1.5 mg/kg) combination in Group III. All the patients' sedation levels were assessed with the Ramsey Sedation Scale (RSS). Their recovery was assessed with the Aldrete and Numerical Rating Scale Score (NRS) at 10 min intervals. Results. The total doses of propofol administered to the patients in the three groups in this study were as follows: 375 mg in Group I, 150 mg in Group II, and 245 mg in Group III. Conclusion. It was observed that, in the patients undergoing ERCP, administration of propofol in combination with an opioid provided effective and reliable sedation, reduced the total dose of propofol, increased the practitioner satisfaction, decreased the pain level, and provided hemodynamic stability compared to the administration of propofol alone. PMID:26576424

Effect of High-Dose vs Standard-Dose Multivitamin Supplementation at the Initiation of HAART on HIV Disease Progression and Mortality in Tanzania

PubMed Central

Isanaka, Sheila; Mugusi, Ferdinand; Hawkins, Claudia; Spiegelman, Donna; Okuma, James; Aboud, Said; Guerino, Chalamilla; Fawzi, Wafaie W.

2013-01-01

Context Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART. Objective To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART. Design, Setting, and Participants A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. Intervention The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance. Main Outcome Measure The composite of HIV disease progression or death from any cause. Results The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96–1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11–1.87) vs standard-dose supplementation. Conclusion In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels. Trial Registration clinicaltrials.gov Identifier: NCT00383669 PMID:23073950

[Nephro-protective effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats].

PubMed

Kuang, Qiao-Ting; Zhao, Jing-Jing; Ye, Chun-Ling; Wang, Jing-Ru; Ye, Kai-He; Zhang, Xiao-Qi; Wang, Ying; Ye, Wen-Cai

2012-01-01

To investigate the nephro-protective effects of total triterpenoids from Psidium guajava leaves (TTPGL) on type 2 diabetic rats. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) and a high-fat diet. Diabetic rats were divided into five groups: diabetic model control, low-dose TTPGL-treated (60 mg/kg, L-TTPGL), medium-dose TTPGL-treated (120 mg/kg, M-TTPGL), high-dose TTPGL-treated (240 mg/kg, H-TTPGL) and rosiglitazone-treated (3 mg/kg, RSG). The rats received daily treatment for six weeks. At the end of the period,the levels of fasting blood glucose (FPG), fasting insulin (FINS), creatinine (Cr) and blood urea nitrogen (BUN) in serum were measured. Kidneys for histopathological evaluation were stained with Hematoxylin and Eosin (HE). Compared with normal control group, the level of FPG was increased, the insulin and insulin sensitivity index were decreased in the model group; The levels of BUN and Cr were increased with histopathological changes related to diabetic nephropathy in the kidney, which were the glomerular endothelium and mesangial cell proliferation, capillary narrowed, the base-membrane incrassation, glomerular swelling, cysts narrowed and tubules edema. Compared with the model group, the levels of FPG were decreased, serum insulin and insulin sensitivity index were increased significantly in M-TTPGL and H-TTPGL groups (P<0.01 or P<0.05); The levels of BUN and Cr were decreased significantly (P<0.01 or P<0.05) and the renal structural damages were improved significantly. TTPGL could decrease the level of blood glucose of diabetic rat effectively, increase the insulin sensitivity index and protect renal lesions in diabetic rats.

Expression of Genes Associated with DNA Damage Sensing in Human Fibroblasts Exposed to Low-dose-rate Gamma Rays

NASA Technical Reports Server (NTRS)

Zhang, Ye; Mehta, Satish; Hammond, Diane; Pierson, Duane; Jeevarajan, Antony; Cucinotta, Francis; Rohde, Larry; Wu, Honglu

2007-01-01

Understanding of the molecular response to low-dose and low-dose-rate radiation exposure is essential for the extrapolation of high-dose radiation risks to those at dose levels relevant to space and other environmental concerns. Most of the reported studies of gene expressions induced by low-dose or low-dose-rate radiation were carried out on exponentially growing cells. In the present study, we analyzed expressions of 84 genes associated with DNA damage sensing using real time PCR in human fibroblasts in mostly G1 phase of the cell cycle. The cells were exposed continuously to gamma rays at a dose rate of 0.8 cGy/hr for 1, 2, 6 or 24 hrs at 37 C throughout the exposure. The total RNA was isolated immediately after the exposure was terminated. Of the 84 genes, only a few showed significant changes of the expression level. Some of the genes (e.g. DDit3 and BTG2) were found to be up or down regulated only after a short period of exposure, while other genes (e.g. PRKDC) displayed a highest expression level at the 24 hr time point. The expression profiles for the exposed cells which had a smaller portion of G1 cells indicated more cell cycle signaling and DNA repair genes either up or down regulated. Interestingly, the panel of genes changed from radiation exposure in G1 cells is different from the panel in cells having less G1 arrest cells. The gene expression profile of the cells responding to low-dose-radiation insult apparently depends on the cell growth stage. The response pathway in G1 cells may differ from that in exponentially growing cells.

Calculated organ doses from selected prostate treatment plans using Monte Carlo simulations and an anatomically realistic computational phantom

PubMed Central

Bednarz, Bryan; Hancox, Cindy; Xu, X George

2012-01-01

There is growing concern about radiation-induced second cancers associated with radiation treatments. Particular attention has been focused on the risk to patients treated with intensity-modulated radiation therapy (IMRT) due primarily to increased monitor units. To address this concern we have combined a detailed medical linear accelerator model of the Varian Clinac 2100 C with anatomically realistic computational phantoms to calculate organ doses from selected treatment plans. This paper describes the application to calculate organ-averaged equivalent doses using a computational phantom for three different treatments of prostate cancer: a 4-field box treatment, the same box treatment plus a 6-field 3D-CRT boost treatment and a 7-field IMRT treatment. The equivalent doses per MU to those organs that have shown a predilection for second cancers were compared between the different treatment techniques. In addition, the dependence of photon and neutron equivalent doses on gantry angle and energy was investigated. The results indicate that the box treatment plus 6-field boost delivered the highest intermediate- and low-level photon doses per treatment MU to the patient primarily due to the elevated patient scatter contribution as a result of an increase in integral dose delivered by this treatment. In most organs the contribution of neutron dose to the total equivalent dose for the 3D-CRT treatments was less than the contribution of photon dose, except for the lung, esophagus, thyroid and brain. The total equivalent dose per MU to each organ was calculated by summing the photon and neutron dose contributions. For all organs non-adjacent to the primary beam, the equivalent doses per MU from the IMRT treatment were less than the doses from the 3D-CRT treatments. This is due to the increase in the integral dose and the added neutron dose to these organs from the 18 MV treatments. However, depending on the application technique and optimization used, the required MU values for IMRT treatments can be two to three times greater than 3D CRT. Therefore, the total equivalent dose in most organs would be higher from the IMRT treatment compared to the box treatment and comparable to the organ doses from the box treatment plus the 6-field boost. This is the first time when organ dose data for an adult male patient of the ICRP reference anatomy have been calculated and documented. The tools presented in this paper can be used to estimate the second cancer risk to patients undergoing radiation treatment. PMID:19671968

Calculated organ doses from selected prostate treatment plans using Monte Carlo simulations and an anatomically realistic computational phantom

NASA Astrophysics Data System (ADS)

Bednarz, Bryan; Hancox, Cindy; Xu, X. George

2009-09-01

There is growing concern about radiation-induced second cancers associated with radiation treatments. Particular attention has been focused on the risk to patients treated with intensity-modulated radiation therapy (IMRT) due primarily to increased monitor units. To address this concern we have combined a detailed medical linear accelerator model of the Varian Clinac 2100 C with anatomically realistic computational phantoms to calculate organ doses from selected treatment plans. This paper describes the application to calculate organ-averaged equivalent doses using a computational phantom for three different treatments of prostate cancer: a 4-field box treatment, the same box treatment plus a 6-field 3D-CRT boost treatment and a 7-field IMRT treatment. The equivalent doses per MU to those organs that have shown a predilection for second cancers were compared between the different treatment techniques. In addition, the dependence of photon and neutron equivalent doses on gantry angle and energy was investigated. The results indicate that the box treatment plus 6-field boost delivered the highest intermediate- and low-level photon doses per treatment MU to the patient primarily due to the elevated patient scatter contribution as a result of an increase in integral dose delivered by this treatment. In most organs the contribution of neutron dose to the total equivalent dose for the 3D-CRT treatments was less than the contribution of photon dose, except for the lung, esophagus, thyroid and brain. The total equivalent dose per MU to each organ was calculated by summing the photon and neutron dose contributions. For all organs non-adjacent to the primary beam, the equivalent doses per MU from the IMRT treatment were less than the doses from the 3D-CRT treatments. This is due to the increase in the integral dose and the added neutron dose to these organs from the 18 MV treatments. However, depending on the application technique and optimization used, the required MU values for IMRT treatments can be two to three times greater than 3D CRT. Therefore, the total equivalent dose in most organs would be higher from the IMRT treatment compared to the box treatment and comparable to the organ doses from the box treatment plus the 6-field boost. This is the first time when organ dose data for an adult male patient of the ICRP reference anatomy have been calculated and documented. The tools presented in this paper can be used to estimate the second cancer risk to patients undergoing radiation treatment.

Immunological Effect of aGV Rabies Vaccine Administered Using the Essen and Zagreb Regimens: A Double-Blind, Randomized Clinical Trial.

PubMed

Miao, Li; Shi, Liwei; Yang, Yi; Yan, Kunming; Sun, Hongliang; Mo, Zhaojun; Li, Li

2018-04-01

This study evaluated the immunological effect of an aGV rabies virus strain using the Essen and Zagreb immunization programs. A total of 1,944 subjects were enrolled and divided into three groups: the Essen test group, Essen control group, and Zagreb test group. Neutralizing antibody levels and antibody seroconversion rates were determined at 7 and 14 days after the initial inoculations and then 14 days after the final inoculation in all of the subjects. The seroconversion rates for the Essen test group, Essen control group, and Zagreb test group, which were assessed 7 days after the first dosing in a susceptible population, were 35.74%, 26.92%, and 45.49%, respectively, and at 14 days, the seroconversion rates in this population were 100%, 100%, and 99.63%, respectively. At 14 days after the final dosing, the seroconversion rates were 100% in all three of the groups. The neutralizing serum antibody levels of the Essen test group, Essen control group, and Zagreb test group at 7 days after the first dosing in the susceptible population were 0.37, 0.26, and 0.56 IU/mL, respectively, and at 14 days after the initial dosing, these levels were 16.71, 13.85, and 16.80 IU/mL. At 14 days after the final dosing, the neutralizing antibody levels were 22.9, 16.3, and 18.62 IU/mL, respectively. The results of this study suggested that the aGV rabies vaccine using the Essen program resulted in a good serum immune response, and the seroconversion rates and the neutralizing antibody levels generated with the Zagreb regimen were higher than those with the Essen regimen when measured 7 days after the first dose.

PERSONNEL NEUTRON DOSIMETER

DOEpatents

Fitzgerald, J.J.; Detwiler, C.G. Jr.

1960-05-24

A description is given of a personnel neutron dosimeter capable of indicating the complete spectrum of the neutron dose received as well as the dose for each neutron energy range therein. The device consists of three sets of indium foils supported in an aluminum case. The first set consists of three foils of indium, the second set consists of a similar set of indium foils sandwiched between layers of cadmium, whereas the third set is similar to the second set but is sandwiched between layers of polyethylene. By analysis of all the foils the neutron spectrum and the total dose from neutrons of all energy levels can be ascertained.

The HGF/c-MET Axis as a Critical Driver of Resistance to Androgen Suppression in Metastatic Castrate-Resistant Prostate Cancer

DTIC Science & Technology

2015-10-01

HGF and/or various treatment doses of cabozantinib ( Cabo ) in MET high/AR-negative prostate cancer cells for 24 hours. Subtask 4: Assess whether c...multityrosine kinase inhibitor cabozantinib ( Cabo ) as indicated. Left panel is representative pictures of indicated treatment results by fluorescent...phospho-MET and total MET protein levels. (C) Invasion assays were performed in the presence of HGF and/or various treatment doses of cabozantinib ( Cabo

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

PubMed

Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Crockett, R S; Howes, John; Darpo, Borje; Zhou, Meijian; Weis, Holger; Friedhoff, Lawrence

2016-11-01

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C max and was slowly eliminated (mean t 1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues. © 2016, The American College of Clinical Pharmacology.

First-in-human study of the toxicity, pharmacokinetics, and pharmacodynamics of CG200745, a pan-HDAC inhibitor, in patients with refractory solid malignancies.

PubMed

Kim, Kyu-pyo; Park, Seong Joon; Kim, Jeong-Eun; Hong, Yong Sang; Lee, Jae-Lyun; Bae, Kyun-Seop; Cha, Hyunju; Kwon, Sool-Ki; Ro, Seonggu; Cho, JoongMyung; Kim, Tae Won

2015-10-01

The aim of the present study was to assess the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and efficacy of single and multiple doses of intravenous CG200745, a novel histone deacetylase (HDAC) inhibitor, in patients with advanced solid malignancies. Two to six patients received intravenous CG200745 according to the 2 + 4 dose-escalating method. This first-in-human trial was comprised of two parts: Part 1 was a single ascending dose, and Part 2 was multiple ascending doses weekly for 3 weeks, and then 1 week off. For the first cycle, pharmacokinetic sampling for CG200745 and pharmacodynamic sampling for acetylated histone H4 in peripheral blood mononuclear cells (PBMCs) were performed on day 1 for Part 1 and on days 1 and 15 for Part 2. Examination of acetylated histone H4 in pre- and post-biopsy samples was performed in accessible patients. In all, 28 patients were treated at 13 dose levels (1.8-250 mg/m(2)) and received a total of 71 cycles of CG200745. Hematologic toxicities included grade 3/4 neutropenia (22.2 %) that did not last a week and non-hematologic toxicities included fatigue (22.2 %) and anorexia (16.7 %) that did not exceed grade 2. No dose-limiting toxic effects were noted. Dose proportionality was observed for both the maximum concentration and area under the curve. The elimination half-life was 5.67 ± 2.69 h (mean ± standard deviation). An increase in PBMC acetylated histone H4 was observed at dose levels up to 51 mg/m(2), which plateaued at higher dose levels. At 24 h, 75 % of patients (6/8) showed higher relative acetylation in tumor tissue compared to PBMCs. Although there was no partial or complete response, 57.1 % of patients (16/28) had stable disease that lasted at least 6 weeks. CG200745 can be safely administered at effective dose levels that inhibit HDAC in PBMCs and tumor tissue. Although MTD was not reached, further escalation was not performed because acetylated histone H4 plateaued at dose levels higher than 51 mg/m(2). Additional phase II trials are recommended at 250 mg/m(2).

[Influence of n-hexane on vascular endothelial active substances in brain tissue in mice].

PubMed

Lin, L; Zhang, Z Q; Zhang, C Z

2017-01-20

Objective: To investigate the influence of n - hexane on vascular endothelial active substances in brain tissue in mice and its significance. Methods: A total of 48 healthy Kunming mice were randomly divided into high - dose exposure group, middle - dose exposure group, low - dose exposure group, and control group, with 12 mice in each group. All groups except the control group were exposed to n - hexane via static inhalation (0.035 g/L, 0.018 g/L, and 0.009 g/L for the high - , middle - , and low - dose exposure groups, respectively) 4 hours a day for 21 days. the mice in the control groups were not exposed to n - hexane. After the exposure, the lev-els of endothelin - 1 (ET - 1) , nitric oxide (NO) , and angiotensin II (Ang II) in brain tissue were measured in all groups. Results: There were significant differences in the levels of ET - 1, NO, and Ang II between the three ex-posure groups and the control group ( P <0.05). Compared with the control group, the high - and middle - dose expo-sure group had significant increases in the levels of ET - 1 and Ang II and the high - dose exposure group had a sig-nificant reduction in the level of NO ( P <0.05 or P <0.01). Conclusion: n - Hexane can affect the vascular endothe-lial active substances in brain tissue in mice, and the changes and imbalance in vascular endothelial active sub-stances may be one of the reasons for central nervous system impairment caused by n - hexane.

Hypovitaminosis D in Bariatric Surgery: A Systematic Review of Observational Studies

PubMed Central

Chakhtoura, M; Nakhoul, N; Shawwa, K; Mantzoros, C; El Hajj Fuleihan, G

2016-01-01

Background Obesity is a public health problem that carries global and substantial social and economic burden. Relative to non-surgical interventions, bariatric surgery has the most substantial and lasting impact on weight loss. However, it leads to a number of nutritional deficiencies requiring long term supplementation. Objectives The aims of this paper are to review 25-hydroxyvitamin D [25(OH)D] status pre and post - bariatric surgery, describe the dose response of vitamin D supplementation, and assess the effect of the surgical procedure on 25(OH)D level following supplementation. Methods We searched Medline, PubMed, the Cochrane Library and EMBASE, for relevant observational studies published in English, from 2000–April 2015. The identified references were reviewed, in duplicate and independently, by two reviewers. Results We identified 51 eligible observational studies assessing 25(OH)D status pre and/or post bariatric surgery. Mean pre-surgery 25(OH)D level was below 30 ng/ml in 29 studies and 17 of these studies showed mean 25(OH)D levels ≤ 20 ng/ml. Mean 25(OH)D levels remained below 30 ng/ml following bariatric surgery despite various vitamin D replacement regimens, with only few exceptions. The increase in postoperative 25(OH)D levels tended to parallel increments in vitamin D supplementation dose but varied widely across studies. An increase in 25(OH)D level by 9–13 ng/ml was achieved when vitamin D deficiency was corrected using vitamin D replacement doses of 1,100–7,100 IU/day, in addition to the usual maintenance equivalent daily dose of 400 – 2,000 IU (total equivalent daily dose 1,500–9,150 IU). There was no difference in mean 25(OH)D level following supplementation between malabsorptive/ combination procedures and restrictive procedures. Conclusion Hypovitaminosisis D persists in obese patients undergoing bariatric surgery, despite various vitamin D supplementation regimens. Further research is needed to determine the optimal vitamin D dose to reach desirable 25(OH)D levels in this population, and to demonstrate whether this dose varies according to the surgical procedure. PMID:26805016

Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

DOE PAGES

Stark, Karolina; Scott, David E.; Tsyusko, Olga; ...

2015-04-30

Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad ( Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments didmore » not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.« less

Ingestion dose from 238U, 232Th, 226Ra, 40K and 137Cs in cereals, pulses and drinking water to adult population in a high background radiation area, Odisha, India.

PubMed

Lenka, Pradyumna; Sahoo, S K; Mohapatra, S; Patra, A C; Dubey, J S; Vidyasagar, D; Tripathi, R M; Puranik, V D

2013-03-01

A natural high background radiation area is located in Chhatrapur, Odisha in the eastern part of India. The inhabitants of this area are exposed to external radiation levels higher than the global average background values, due to the presence of uranium, thorium and its decay products in the monazite sands bearing placer deposits in its beaches. The concentrations of (232)Th, (238)U, (226)Ra, (40)K and (137)Cs were determined in cereals (rice and wheat), pulses and drinking water consumed by the population residing around this region and the corresponding annual ingestion dose was calculated. The annual ingestion doses from cereals, pulses and drinking water varied in the range of 109.4-936.8, 10.2-307.5 and 0.5-2.8 µSv y(-1), respectively. The estimated total annual average effective dose due to the ingestion of these radionuclides in cereals, pulses and drinking water was 530 µSv y(-1). The ingestion dose from cereals was the highest mainly due to a high consumption rate. The highest contribution of dose was found to be from (226)Ra for cereals and drinking water and (40)K was the major dose contributor from the intake of pulses. The contribution of man-made radionuclide (137)Cs to the total dose was found to be minimum. (226)Ra was found to be the largest contributor to ingestion dose from all sources.

High-level dietary cadmium exposure is associated with global DNA hypermethylation in the gastropod hepatopancreas

PubMed Central

Popescu, Cristina; Draghici, George A.; Andrica, Florina-Maria; Privistirescu, Ionela A.; Gergen, Iosif I.; Stöger, Reinhard

2017-01-01

5-methylcytosine (5mC) is a key epigenetic mark which influences gene expression and phenotype. In vertebrates, this epigenetic mark is sensitive to Cd exposure, but there is no information linking such an event with changes in global 5mC levels in terrestrial gastropods despite their importance as excellentecotoxicological bioindicators of metal contamination. Therefore, we first evaluated total 5mC content in DNA of the hepatopancreas of adult Cantareus aspersus with the aim to determine whether this epigenetic mark is responsive to Cd exposure. The experiment was conducted under laboratory conditions and involved a continuous exposure, multiple dose- and time-point (14, 28, and 56 days) study design. Hepatopancreas cadmium levels were measured using Flame Atomic Absorption Spectrometry and the percentage of 5-mC in samples using an ELISA-based colorimetric assay. Snail death rates were also assessed. Our results, for the first time, reveal the presence of 5mC in C. aspersus and provide evidence for Cd-induced changes in global 5mC levels in DNA of gastropods and mollusks. Although less sensitive than tissue accumulation, DNA methylation levels responded in a dose- and time-dependent manner to dietary cadmium, with exposure dose having a much stronger effect than exposure duration. An obvious trend of increasing 5mC levels was observed starting at 28 days of exposure to the second highest dose and this trend persisted at the two highest treatments for close to one month, when the experiment was terminated after 56 days. Moreover, a strong association was identified between Cd concentrations in the hepatopancreas and DNA methylation levels in this organ. These data indicate an overall trend towards DNA hypermethylation with elevated Cd exposure. No consistent lethal effect was observed, irrespective of time point and Cd-dosage. Overall, our findings suggest that the total 5mC content in DNA of the hepatopancreas of land snails is responsive to sublethal Cd exposure and give new insights into invertebrate environmental epigenetics. PMID:28877233

High dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis

PubMed Central

Imam, Mohamad H.; Sinakos, Emmanouil; Gossard, Andrea A.; Kowdley, Kris V.; Luketic, Velimir A. C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Keach, Jill; DeCook, Alisha C.; Enders, Felicity; Lindor, Keith D.

2013-01-01

Background Ursodeoxycholic acid (UDCA) in a dose of 28–30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. Aim Our aim was to compare the risk of adverse clinical endpoints in patients with varying disease status. Methods We reviewed records from patients previously enrolled in a study evaluating the effects of high-dose (28–30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histologic stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, esophageal varices and cholangiocarcinoma was sought. Results One hundred fifty patients were included of which 49 patients developed endpoints. There was an increased development of endpoints amongst patients using UDCA vs. placebo (14 vs. 4, p = 0.0151) with early histologic disease (stage 1–2, n = 88) but not with late stage (stage 3–4, n = 62) disease (17 vs. 14, p = 0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, p = 0.0008) with normal bilirubin levels (total bilirubin ≤ 1.0 mg/dl) but not in patients with elevated bilirubin levels (15 vs. 16, p = 0.6018). Among patients not reaching endpoints 31.68% had normalization of their alkaline phosphatase levels as compared to 14.29% in patients who reached endpoints (p = 0.073). Conclusion The increased risk of adverse events with UDCA treatment as compared to placebo is only apparent in patients with early histologic stage disease or normal total bilirubin. PMID:21957881

Partially hydrolyzed guar gum supplement reduces high-fat diet increased blood lipids and oxidative stress and ameliorates FeCl3-induced acute arterial injury in hamsters

PubMed Central

Kuo, Dar-Chih; Hsu, Shih-Ping; Chien, Chiang-Ting

2009-01-01

Increased reactive oxygen species (ROS) and hyperlipidemia can promote arterial thrombus. We evaluated the potential of a partially hydrolyzed guar gum (PHGG) as dietary fiber on lipid profiles and FeCl3-induced arterial thrombosis in the high fat-diet fed hamsters. Our in vitro results found that PHGG is efficient to scavenge O2-•, H2O2, and HOCl. High fat-diet increased plasma triglyceride, total cholesterol, LDL, VLDL, methylguanidine and dityrosine level and accelerated FeCl3-induced arterial thrombosis formation (from 463 ± 51 to 303 ± 45 sec). Low dose PHGG supplement significantly decreased the total cholesterol, LDL, methylguanidine and dityrosine level and delayed the time for arterial thrombosis formation (528 ± 75 sec). High dose PHGG supplement decreased the level in triglyceride, total cholesterol, LDL and VLDL and further delayed the time for arterial thrombus (671 ± 36 sec). The increased Bax protein and decreased Bcl-2 and HSP-70 protein expression was found in the carotid and femoral arteries of high fat-diet hamsters. Low and high dose of PHGG supplement decreased Bax expression and increased Bcl-2 and HSP-70 protein expression. We found that FeCl3 significantly enhanced intercellular adhesion molecule-1 and 4-hydroxynonenal expression in the endothelial site of damaged artery after 150-sec FeCl3 stimulation. PHGG supplement decreased the endothelial ICAM-1 and 4-hydroxynonenal expression after 150-sec FeCl3 stimulation. Based on these results, we conclude that PHGG supplement can increase antioxidant protein expression and thus decrease oxidative stress induced arterial injury. PMID:19272178

The effects of high dose of two manganese supplements (organic and inorganic) on the rumen microbial ecosystem.

PubMed

Kišidayová, Svetlana; Pristaš, Peter; Zimovčáková, Michaela; Blanár Wencelová, Monika; Homol'ová, Lucia; Mihaliková, Katarína; Čobanová, Klaudia; Grešáková, Ľubomíra; Váradyová, Zora

2018-01-01

Little is known about the effects of the high dose and types of manganese supplements on rumen environment at manganese intake level close above the limit of 150 mg/kg of dry feed matter. The effects of high dose of two manganese supplements (organic and inorganic) on rumen microbial ecosystem after four months of treatment of 18 lambs divided into three treatment groups were studied. We examined the enzyme activities (α-amylase, xylanase, and carboxymethyl cellulase), total and differential microscopic counts of rumen ciliates, total microscopic counts of bacteria, and fingerprinting pattern of the eubacterial and ciliates population analyzed by PCR-DGGE. Lambs were fed a basal diet with a basal Mn content (34.3 mg/kg dry matter; control) and supplemented either with inorganic manganous sulfate or organic Mn-chelate hydrate (daily 182.7, 184 mg/kg dry matter of feed, respectively). Basal diet, offered twice daily, consisted of ground barley and hay (268 and 732 g/kg dry matter per animal and day). The rumens of the lambs harbored ciliates of the genera of Entodinium, Epidinium, Diplodinium, Eudiplodinium, Dasytricha, and Isotricha. No significant differences between treatment groups were observed in the total ciliate number, the number of ciliates at the genus level, as well as the total number of bacteria. Organic Mn did decrease the species richness and diversity of the eubacterial population examined by PCR-DGGE. No effects of type of Mn supplement on the enzyme activities were observed. In comparison to the control, α-amylase specific activities were decreased and carboxymethyl-cellulase specific activities were increased by the Mn supplements. Xylanase activities were not influenced. In conclusion, our results suggested that the intake of tested inorganic and organic manganese supplements in excess may affect the specific groups of eubacteria. More studies on intake of Mn supplements at a level close to the limit can reveal if the changes in microbial population impact remarkably the other rumen enzymatic activities.

The effects of high dose of two manganese supplements (organic and inorganic) on the rumen microbial ecosystem

PubMed Central

Pristaš, Peter; Zimovčáková, Michaela; Blanár Wencelová, Monika; Homol'ová, Lucia; Mihaliková, Katarína; Čobanová, Klaudia; Grešáková, Ľubomíra; Váradyová, Zora

2018-01-01

Little is known about the effects of the high dose and types of manganese supplements on rumen environment at manganese intake level close above the limit of 150 mg/kg of dry feed matter. The effects of high dose of two manganese supplements (organic and inorganic) on rumen microbial ecosystem after four months of treatment of 18 lambs divided into three treatment groups were studied. We examined the enzyme activities (α-amylase, xylanase, and carboxymethyl cellulase), total and differential microscopic counts of rumen ciliates, total microscopic counts of bacteria, and fingerprinting pattern of the eubacterial and ciliates population analyzed by PCR-DGGE. Lambs were fed a basal diet with a basal Mn content (34.3 mg/kg dry matter; control) and supplemented either with inorganic manganous sulfate or organic Mn-chelate hydrate (daily 182.7, 184 mg/kg dry matter of feed, respectively). Basal diet, offered twice daily, consisted of ground barley and hay (268 and 732 g/kg dry matter per animal and day). The rumens of the lambs harbored ciliates of the genera of Entodinium, Epidinium, Diplodinium, Eudiplodinium, Dasytricha, and Isotricha. No significant differences between treatment groups were observed in the total ciliate number, the number of ciliates at the genus level, as well as the total number of bacteria. Organic Mn did decrease the species richness and diversity of the eubacterial population examined by PCR-DGGE. No effects of type of Mn supplement on the enzyme activities were observed. In comparison to the control, α-amylase specific activities were decreased and carboxymethyl-cellulase specific activities were increased by the Mn supplements. Xylanase activities were not influenced. In conclusion, our results suggested that the intake of tested inorganic and organic manganese supplements in excess may affect the specific groups of eubacteria. More studies on intake of Mn supplements at a level close to the limit can reveal if the changes in microbial population impact remarkably the other rumen enzymatic activities. PMID:29324899

The effects of UV radiation during the vegetative period on antioxidant compounds and postharvest quality of broccoli (Brassica oleracea L.).

PubMed

Topcu, Yasin; Dogan, Adem; Kasimoglu, Zehra; Sahin-Nadeem, Hilal; Polat, Ersin; Erkan, Mustafa

2015-08-01

In this study, the effects of supplementary UV radiation during the vegetative period on antioxidant compounds, antioxidant activity and postharvest quality of broccoli heads during long term storage was studied. The broccolis were grown under three different doses of supplementary UV radiation (2.2, 8.8 and 16.4 kJ/m(2)/day) in a soilless system in a glasshouse. Harvested broccoli heads were stored at 0 °C in modified atmosphere packaging for 60 days. The supplementary UV radiation (280-315 nm) during the vegetative period significantly decreased total carotenoid, the chlorophyll a and chlorophyll b content but increased the ascorbic acid, total phenolic and flavonoid contents of broccolis. All supplementary UV treatments slightly reduced the antioxidant activity of the broccolis, however, no remarkable change was observed between 2.2 and 8.8 kJ/m(2) radiation levels. The sinigrin and glucotropaeolin contents of the broccolis were substantially increased by UV treatments. The prolonged storage period resulted in decreased ascorbic acid, total phenolic and flavonoid contents, as well as antioxidant activity. Discoloration of the heads, due to decreased chlorophyll and carotenoid contents, was also observed with prolonged storage duration. Glucosinolates levels showed an increasing tendency till the 45th day of storage, and then their levels started to decline. The weight loss of broccoli heads during storage progressively increased with storage time in all treatments. Total soluble solids, solids content and titratable acidity decreased continuously during storage. Titratable acidity was not affected by UV radiation doses during the storage time whereas soluble solids and solids content (dry matter) were significantly affected by UV doses. Supplementary UV radiation increased the lightness (L*) and chroma (C*) values of the broccoli heads. Pre-harvest UV radiation during vegetative period seems to be a promising tool for increasing the beneficial health components of broccolis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

An In Vivo Study of Low-Dose Intra-Articular Tranexamic Acid Application with Prolonged Clamping Drain Method in Total Knee Replacement: Clinical Efficacy and Safety.

PubMed

Sa-ngasoongsong, Paphon; Chanplakorn, Pongsthorn; Wongsak, Siwadol; Uthadorn, Krisorn; Panpikoon, Tanapong; Jittorntam, Paisan; Aryurachai, Katcharin; Angchaisukisiri, Pantap; Kawinwonggowit, Viroj

2015-01-01

Recently, combined intra-articular tranexamic acid (IA-TXA) injection with clamping drain method showed efficacy for blood loss and transfusion reduction in total knee replacement (TKR). However, until now, none of previous studies revealed the effect of this technique on pharmacokinetics, coagulation, and fibrinolysis. An experimental study was conducted, during 2011-2012, in 30 patients undergoing unilateral TKR. Patients received IA-TXA application and then were allocated into six groups regarding clamping drain duration (2-, 4-, 6-, 8-, 10-, and 12-hours). Blood and drainage fluid were collected to measure tranexamic acid (TXA) level and related coagulation and fibrinolytic markers. Postoperative complication was followed for one year. There was no significant difference of serum TXA level at 2 hour and 24 hour among groups (p < 0.05). Serum TXA level at time of clamp release was significantly different among groups with the highest level at 2 hour (p < 0.0001). There was no significant difference of TXA level in drainage fluid, postoperative blood loss, blood transfusion, and postoperative complications (p < 0.05). Low-dose IA-TXA application in TKR with prolonged clamping drain method is a safe and effective blood conservative technique with only minimal systemic absorption and without significant increase in systemic absorption over time.

Novel Measure of Opioid Dose and Costs of Care for Diabetes Mellitus: Opioid Dose and Health Care Costs.

PubMed

Gautam, Santosh; Franzini, Luisa; Mikhail, Osama I; Chan, Wenyaw; Turner, Barbara J

2016-03-01

Diabetes mellitus (DM) has well known costly complications but we hypothesized that costs of care for chronic pain treated with opioid analgesic (OA) medications would also be substantial. In a statewide, privately insured cohort of 29,033 adults aged 18 to 64 years with DM and noncancer pain who filled OA prescription(s) from 2008 to 2012, our outcomes were costs for specific health care services and total costs per 6-month intervals after the first filled OA prescription. Average daily OA dose (4 categories) and total dose (quartiles) in morphine-equivalent milligrams were calculated per 6-month interval after the first OA prescription and combined into a novel OA dose measure. Associations of OA measures with costs of care (n = 126,854 6-month intervals) were examined using generalized estimating equations adjusted for clinical conditions, psychotherapeutic drugs, and DM treatment. Incremental costs for each type of health care service and total cost of care increased progressively with average daily and total OA dose versus no OAs. The combined OA measure identified the highest incremental total costs per 6-month interval that were increased by $8,389 for 50- to 99-mg average daily dose plus >900 mg total dose and, by $9,181 and $9,958 respectively, for ≥100 mg average daily dose plus 301- to 900-mg or >900 mg total dose. In this statewide DM cohort, total health care costs per 6-month interval increased progressively with higher average daily OA dose and with total OA dose but the greatest increases of >$8,000 were distinguished by combinations of higher average daily and total OA doses. The higher costs of care for opioid-treated patients appeared for all types of services and likely reflects multiple factors including morbidity from the underlying cause of pain, care and complications related to opioid use, and poorer control of diabetes as found in other studies. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia.

PubMed

Vahdat, L; Wong, E T; Wile, M J; Rosenblum, M; Foley, K M; Warrell, R P

1994-11-15

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.

Simulation of parabolic reflectors for ultraviolet phototherapy

NASA Astrophysics Data System (ADS)

Grimes, David Robert

2016-08-01

Ultraviolet (UVR) phototherapy is widely used to treat an array of skin conditions, including psoriasis, eczema and vitiligo. For such interventions, a quantified dose is vital if the treatment is to be both biologically effective and to avoid the detrimental effects of over-dosing. As dose is absorbed at surface level, the orientation of patient site with respect to the UVR lamps modulates effective dose. Previous investigations have modelled this behaviour, and examined the impact of shaped anodized aluminium reflectors typically placed around lamps in phototherapy cabins. These mirrors are effective but tend to yield complex patterns of reflection around the cabin which can result in substantial dose inhomogeneity. There has been some speculation over whether using the reflective property of parabolic mirrors might improve dose delivery or homogeneity through the treatment cabin. In this work, the effects of parabolic mirrors are simulated and compared with standard shaped mirrors. Simulation results strongly suggest that parabolic reflectors reduce total irradiance relative to standard shaped reflectors, and have a negligible impact on dose homogeneity.

Chronic toxicity of a mixture of chlorinated alkanes and alkenes in ICR mice.

PubMed

Wang, Fun-In; Kuo, Min-Liang; Shun, Chia-Tung; Ma, Yee-Chung; Wang, Jung-Der; Ueng, Tzuu-Huei

2002-02-01

The aim of this study was to determine the chronic toxicity of a mixture of chlorinated alkanes and alkenes (CA) consisting of chloroform, 1,1-dichloroethane, 1,1-dichloroethylene, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene. These chlorinated organic solvents were present in the underground water near an electronic appliances manufactory in Taoyuan, Taiwan. Male and female weanling ICR mice were treated with low-, medium-, and high-dose CA mixtures in drinking water for 16 and 18 mo, respectively. A significant number of male mice treated with the high-dose CA mixture developed tail alopecia and deformation, which was not prominent in CA-treated female mice. Medium- and high-dose CA mixtures induced marginal increases of liver and lung weights, blood urea nitrogen, and serum creatinine levels in male mice. In female mice, the high-dose CA mixture increased liver, kidney, and uterus and ovary total weights, without affecting serum biochemistry parameters. CA mixtures had no effects on the total glutathione content or the level of glutathione S-transferase activity in the livers and kid- neys of male and female mice. Treatments with CA mixtures produced a trend of increasing frequency of hepatocelluar neoplasms in male mice, compared to male and female controls and CA-treated female mice. The high-dose CA mixture induced a significantly higher incidence of mammary adenocarcinoma in female mice. The calculated odds ratios of mammary adenocarcinoma in female mice induced by low-, medium-, and high-dose CA mixtures were 1.14, 1.37, and 3.53 times that of the controls, respectively. The low-dose CA mixture induced a higher incidence of cysts and inflammation in and around the ovaries. This study has demonstrated that the CA mixture is a potential carcinogen to male and female mice. These animal toxicology data may be important in assessing the health effects of individuals exposed to the CA mixture.

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

Reproducibility of three-dimensional cephalometric landmarks in cone-beam and low-dose computed tomography.

PubMed

Olszewski, R; Frison, L; Wisniewski, M; Denis, J M; Vynckier, S; Cosnard, G; Zech, F; Reychler, H

2013-01-01

The purpose of this study is to compare the reproducibility of three-dimensional cephalometric landmarks on three-dimensional computed tomography (3D-CT) surface rendering using clinical protocols based on low-dose (35-mAs) spiral CT and cone-beam CT (I-CAT). The absorbed dose levels for radiosensitive organs in the maxillofacial region during exposure in both 3D-CT protocols were also assessed. The study population consisted of ten human dry skulls examined with low-dose CT and cone-beam CT. Two independent observers identified 24 cephalometric anatomic landmarks at 13 sites on the 3D-CT surface renderings using both protocols, with each observer repeating the identification 1 month later. A total of 1,920 imaging measurements were performed. Thermoluminescent dosimeters were placed at six sites around the thyroid gland, the submandibular glands, and the eyes in an Alderson phantom to measure the absorbed dose levels. When comparing low-dose CT and cone-beam CT protocols, the cone-beam CT protocol proved to be significantly more reproducible for four of the 13 anatomical sites. There was no significant difference between the protocols for the other nine anatomical sites. Both low-dose and cone-beam CT protocols were equivalent in dose absorption to the eyes and submandibular glands. However, thyroid glands were more irradiated with low-dose CT. Cone-beam CT was more reproducible and procured less irradiation to the thyroid gland than low-dose CT. Cone-beam CT should be preferred over low-dose CT for developing three-dimensional bony cephalometric analyses.

Update of a comparative analysis of cost minimization following the introduction of newly available intravenous iron therapies in hospital practice

PubMed Central

Bhandari, Sunil

2011-01-01

Background The clinical need to be able to administer high doses of intravenous iron conveniently as a rapid infusion has been addressed by the recent introduction of ferric carboxymaltose and subsequently iron isomaltoside 1000. Neither requires a test dose. The maximum dose of ferric carboxymaltose is 1000 mg. The maximum dose of iron isomaltoside 1000 is based on 20 mg/kg body weight without a specified ceiling dose, thereby increasing the scope of being able to achieve total iron repletion with a single infusion. This ability to give high doses of iron is important in the context of managing iron deficiency anemia, which is associated with a number of clinical conditions where demands for iron are high. It is also an important component of the strategy as an alternative to blood transfusion. Affordability is a key issue for health services. Recent price changes affecting iron sucrose and ferric carboxymaltose, plus modifications to the manufacturers’ prescribing information, have provoked this update. Methods This study is a comparative analysis of the costs of acquiring and administering the newly available intravenous iron formulations against standard treatments in the hospital setting. The costs include the medication, nursing costs, equipment, and patient transportation. Three dosage levels (600 mg, 1000 mg, and 1600 mg) are considered. Results and conclusion The traditional standard treatments, blood and iron sucrose, cost more than the alternative intravenous iron preparations across the dose spectrum and sensitivities. Low molecular weight iron dextran is the least expensive option at the 1600 mg dose level but has the caveat of a prolonged administration time and requirement for a test dose. At 600 mg and 1000 mg dose levels, both iron isomaltoside 1000 and ferric carboxymaltose are more economical than low molecular weight iron dextran. Iron isomaltoside 1000 is less expensive than ferric carboxymaltose at all dose levels. Newly available iron preparations appear to be clinically promising, cost effective, and practical alternatives to current standards of iron repletion. PMID:22241947

The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients.

PubMed

Sombolos, Kostas; Papaioannou, Anna; Christidou, Fotini; Natse, Taisir; Bamichas, Gerasimos; Gionanlis, Lazaros; Katsaris, George; Progia, Evagelia

2006-01-01

Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0+/-40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B1 (250 mg), vitamin B6 (250 mg) and vitamin B12 (1.5 mg) was administered at the end of hemodialysis. Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8+/-23 micromol/L vs. 22.0+/-17.6 and 15.0+/-4.5 micromol/L, respectively; p<0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p<0.000001). Mean serum tHcy levels were lowest at the end of period C (p<0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 micromol/L. In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.

Significant increase in salivary substance p level after a single oral dose of cevimeline in humans.

PubMed

Suzuki, Yosuke; Itoh, Hiroki; Amada, Kohei; Yamamura, Ryota; Sato, Yuhki; Takeyama, Masaharu

2013-01-01

Cevimeline is a novel muscarinic acetylcholine receptor agonist currently being developed as a therapeutic agent for xerostomia. We examined the effects of cevimeline on salivary and plasma levels of substance-P- (SP-), calcitonin-gene-related-peptide- (CGRP-), and vasoactive-intestinal-polypeptide- (VIP-) like immunoreactive substances (ISs) in humans. An open-labeled crossover study was conducted on seven healthy volunteers. Saliva volume was measured, and saliva and venous blood samples were collected before and 30-240 min after a single oral dose of cevimeline or placebo. Salivary and plasma levels of SP-, CGRP-, and VIP-IS were measured using a highly sensitive enzyme immunoassay. A single oral dose of cevimeline resulted in significant increases in salivary but not plasma SP-IS level compared to placebo. Cevimeline administration did not alter the salivary or plasma levels of CGRP-IS or VIP-IS compared to placebo. Significant increases in salivary volume were observed after cevimeline administration compared to placebo. A significant correlation was observed between the total release of SP-IS and that of salivary volume. These findings suggest an association of SP with the enhancement of salivary secretion by cevimeline.

Significant Increase in Salivary Substance P Level after a Single Oral Dose of Cevimeline in Humans

PubMed Central

Suzuki, Yosuke; Itoh, Hiroki; Amada, Kohei; Yamamura, Ryota; Sato, Yuhki; Takeyama, Masaharu

2013-01-01

Cevimeline is a novel muscarinic acetylcholine receptor agonist currently being developed as a therapeutic agent for xerostomia. We examined the effects of cevimeline on salivary and plasma levels of substance-P- (SP-), calcitonin-gene-related-peptide- (CGRP-), and vasoactive-intestinal-polypeptide- (VIP-) like immunoreactive substances (ISs) in humans. An open-labeled crossover study was conducted on seven healthy volunteers. Saliva volume was measured, and saliva and venous blood samples were collected before and 30–240 min after a single oral dose of cevimeline or placebo. Salivary and plasma levels of SP-, CGRP-, and VIP-IS were measured using a highly sensitive enzyme immunoassay. A single oral dose of cevimeline resulted in significant increases in salivary but not plasma SP-IS level compared to placebo. Cevimeline administration did not alter the salivary or plasma levels of CGRP-IS or VIP-IS compared to placebo. Significant increases in salivary volume were observed after cevimeline administration compared to placebo. A significant correlation was observed between the total release of SP-IS and that of salivary volume. These findings suggest an association of SP with the enhancement of salivary secretion by cevimeline. PMID:23589717

Organ biodistribution of Germanium-68 in rat in the presence and absence of [68Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body radiation dosimetry

PubMed Central

Velikyan, Irina; Antoni, Gunnar; Sörensen, Jens; Estrada, Sergio

2013-01-01

Positron Emission Tomography (PET) and in particular gallium-68 (68Ga) applications are growing exponentially worldwide contributing to the expansion of nuclear medicine and personalized management of patients. The significance of 68Ga utility is reflected in the implementation of European Pharmacopoeia monographs. However, there is one crucial point in the monographs that might limit the use of the generators and consequently expansion of 68Ga applications and that is the limit of 0.001% of Germanium-68 (68Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of 68Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and justification of the 68Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [68Ge]GeCl4 in the absence or presence of [68Ga]Ga-DOTA-TOC. The tissue radioactivity distribution data was extrapolated for the estimation of human organ equivalent doses and total effective dose using Organ Level Internal Dose Assessment Code software (OLINDA/EXM). 68Ge(IV) was evenly distributed among the rat organs and fast renal excretion prevailed. Human organ equivalent dose and total effective dose estimates indicated that the kidneys were the dose-limiting organs (185±54 μSv/MBq for female and 171±38 μSv/MBq for male) and the total effective dose was 15.5±0.1 and 10.7±1.2 μSv/MBq, respectively for female and male. The results of this dosimetry study conclude that the 68Ge(IV) limit currently recommended by monographs could be increased considerably (>100 times) without exposing the patient to harm given the small absorbed doses to normal organs and fast excretion. PMID:23526484

Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation.

PubMed

Wong, Jeffrey Y C; Rosenthal, Joseph; Liu, An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

2009-01-01

Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches.

High-precision γ -ray spectroscopy of the cardiac PET imaging isotope Rb 82 and its impact on dosimetry

DOE PAGES

Nino, M. N.; McCutchan, E. A.; Smith, S. V.; ...

2016-02-01

82Rb is a positron-emitting isotope used in cardiac positron emission tomography (PET) imaging which has been reported to deliver a significantly lower effective radiation dose than analogous imaging isotopes like 201Tl and 99mTc sestamibi. High-quality β-decay data are essential to accurately appraise the total dose received by the patients. A source of 82Sr was produced at the Brookhaven Linac Isotope Producer (BLIP), transported to Argonne National Laboratory, and studied with the Gammasphere facility. Significant revisions have been made to the level scheme of 82Kr including 12 new levels, 50 new γ-ray transitions, and the determination of many new spin assignmentsmore » through angular correlations. Lastly, these new high-quality data allow a precise reappraisal of the β-decay strength function and thus the consequent dose received by patients.« less

Real-time colour pictorial radiation monitoring during coronary angiography: effect on patient peak skin and total dose during coronary angiography.

PubMed

Wilson, Sharon M; Prasan, Ananth M; Virdi, Amy; Lassere, Marissa; Ison, Glenn; Ramsay, David R; Weaver, James C

2016-10-10

The aim of this study was to evaluate whether a real-time (RT) colour pictorial radiation dose monitoring system reduces patient skin and total radiation dose during coronary angiography and intervention. Patient demographics, procedural variables and radiation parameters were recorded before and after institution of the RT skin dose recording system. Peak skin dose as well as traditionally available measures of procedural radiation dose were compared. A total of 1,077 consecutive patients underwent coronary angiography, of whom 460 also had PCI. Institution of the RT skin dose recording system resulted in a 22% reduction in peak skin dose after accounting for confounding variables. Radiation dose reduction was most pronounced in those having PCI but was also seen over a range of subgroups including those with prior coronary artery bypass surgery, high BMI, and with radial arterial access. This was associated with a significant reduction in the number of patients placed at risk of skin damage. Similar reductions in parameters reflective of total radiation dose were also demonstrated after institution of RT radiation monitoring. Institution of an RT skin dose recording reduced patient peak skin and total radiation dose during coronary angiography and intervention. Consideration should be given to widespread adoption of this technology.

Weighted concentration of sup 137 Cs equivalent in foodstuffs in Kuwait from June 1986 to December 1988

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

Bakir, Y.Y.; Sayed, A.M.; Salem, M.S.

1990-06-01

The weighted monthly concentration of {sup 137}Cs equivalent (WMC) for various types of foodstuffs imported from June 1986 to December 1988 are discussed. The data presented are based on total concentration of {sup 137}Cs equivalent. The concentration was found below the disqualifying level applied in Kuwait. The radioactive contamination was higher in milk and baby milk relative to other types of foodstuffs. The calculation of Kuwait's disqualifying levels are based on the annual dose equivalent of 1 mSv (100 mrem). The measured WMC for most types of foodstuffs represents a small fraction to the annual dose limit recommended for themore » general public.« less

Assessment of antidiabetic potential of Cynodon dactylon extract in streptozotocin diabetic rats.

PubMed

Singh, Santosh Kumar; Kesari, Achyut Narayan; Gupta, Rajesh Kumar; Jaiswal, Dolly; Watal, Geeta

2007-11-01

This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extract of Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administration of aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000mg/kg bw of aqueous extract of Cynodon dactylon were evaluated and the dose of 500mg/kg was identified as the most effective dose. It lowers blood glucose level around 31% after 4h of administration in normal rats. The same dose of 500mg/kg produced a fall of 23% in blood glucose level within 1h during glucose tolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250mg/kg bw). Severely diabetic rats were also treated daily with 500mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level. A reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic potential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, in severely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueous extract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.

Ergothioneine prevents endothelial dysfunction induced by mercury chloride.

PubMed

Gökçe, Göksel; Arun, Mehmet Zuhuri; Ertuna, Elif

2018-06-01

Exposure to mercury has detrimental effects on the cardiovascular system, particularly the vascular endothelium. The present study aimed to investigate the effects of ergothioneine (EGT) on endothelial dysfunction induced by low-dose mercury chloride (HgCl 2 ). Agonist-induced contractions and relaxations were evaluated in isolated aortic rings from 3-month-old male Wistar rats treated by intra-muscular injection to caudal hind leg muscle with HgCl 2 (first dose, 4.6 µg/kg; subsequent doses, 0.07 µg/kg/day for 15 days) and optionally with EGT (2 µg/kg for 30 days). Reactive oxygen species (ROS) in aortic rings were measured by means of lucigenin- and luminol-enhanced chemiluminescence. The protein level of endothelial nitric oxide synthase was evaluated by ELISA. Blood glutathione (GSH) and catalase levels, lipid peroxidation and total nitrite were measured spectrophotometrically. The results indicated that low-dose HgCl 2 administration impaired acetylcholine (ACh)-induced relaxation and potentiated phenylephrine- and serotonin-induced contractions in rat aortas. In addition, HgCl 2 significantly increased the levels of ROS in the aortic tissue. EGT prevented the loss of ACh-induced relaxations and the increase in contractile responses. These effects were accompanied by a significant decrease in ROS levels. EGT also improved the ratio of reduced GSH to oxidized GSH and catalase levels with a concomitant decrease in lipid peroxidation. In conclusion, to the best of our knowledge, the present study was the first to report that EGT prevents endothelial dysfunction induced by low-dose HgCl 2 administration. EGT may serve as a therapeutic tool to reduce mercury-associated cardiovascular complications via improving the antioxidant status.

SR-TXRF analysis of trace elements in whole blood and heart of rats: effects of irradiation with low and high doses

NASA Astrophysics Data System (ADS)

Mota, C. L.; Pickler, A.; Braz, D.; Barroso, R. C.; Mantuano, A.; Salata, C.; Ferreira-Machado, S. C.; Lau, C. C.; de Almeida, C. E.

2018-04-01

In the last decades, studies showed that the exposure to low doses of ionizing radiation of the body could sense and activate the cell signaling pathways needed to respond to any induced cellular damage. This procedure reduces cell killing compared with a single dose of high radiation dose. Damage to the vasculature can affect the function of most body organs by restricting blood flow and oxygen to tissues; however, the heart and brain are of main concern. The precise relationship between long-term health effects and low-dose exposures remain poorly understood. Biological markers are powerful tools that can be used to determine dose- response relationships and to estimate risk, especially when dealing with, the effects of low dose exposures in humans. These markers should be specific, sensitive, as well as easy and fast to quantify. Various types of biologic specimens are potential candidates for identifying biomarkers but blood has the advantage of being minimally invasive to obtain. In this study, we propose to apply total reflection X-ray fluorescence to quantify possible chemical elemental concentration (sulfer, iron, zinc, potassium and calcium) changes in blood and heart tissues of Wistar rats after total body irradiation with low (0.1 Gy) and high (2.5 Gy) doses. The fluorescence measurements were carried out at the X-ray Fluorescence beamline in the Brazilian Synchrotron Light Laboratory. The results showed that the irradiated animals with low doses have significant alterations in blood and cardiac tissue when compared with animals that received high doses of radiation. Taken together the analysis of all the elements, we can observe that the radiation induced oxidative stress may be the leading cause for alteration of the elemental level in the studied samples.

Dose-dependent effects of vitamin 1,25(OH)2D3 on oxidative stress and apoptosis.

PubMed

Cakici, Cagri; Yigitbasi, Turkan; Ayla, Sule; Karimkhani, Hadi; Bayramoglu, Feyza; Yigit, Pakize; Kilic, Ertugrul; Emekli, Nesrin

2018-02-08

Background The purpose of this study is to examine the dose-dependent effects of vitamin 1,25(OH)2D3 on apoptosis and oxidative stress. Methods In this study, 50 male Balb/c mice were used as control and experiment groups. The mice were divided into 5 groups each consisting of 10 mice. Calcitriol was intraperitoneally administered as low dose, medium dose, medium-high dose and high dose vitamin D groups (at 0.5, 1, 5 and 10 μg/kg, respectively), for three times a week during 14 days. At the end of the study, annexin V was measured by enzyme-linked immunosorbent assay method, and total antioxidant capacity and total oxidant status values were measured by colorimetric method in serum. Hematoxylin eosin staining was performed in liver tissues and periodic acid schiff staining was performed in kidney tissues. Results While comparing the results of medium-high dose (5 μg/kg) and high dose (10 μg/kg) vitamin D administration to that of the control group, it was observed that serum antioxidant status and annexin V levels decreased and glomerular mesenchial matrix ratio increased in kidney (p<0.05). In addition to these findings, in the group receiving high dose vitamin D (10 μg/kg), it was observed that the damage to the liver increased together with the the oxidative stress index values (p<0.05). Conclusions As a result, this study was the first in the literature to report that use of high-dose vitamin D (10 μg/kg) results in oxidant effect, rather than being an antioxidant, and causes severe histopathological toxicity in the liver and kidney.

Determinants of medication adherence to topical glaucoma therapy.

PubMed

Dreer, Laura E; Girkin, Christopher; Mansberger, Steven L

2012-01-01

To determine the associations between medical, demographic, socioeconomic, and ocular factors and adherence to topical glaucoma ocular hypotensive therapy. One hundred sixteen patients with ocular hypertension or open-angle glaucoma from 2 tertiary glaucoma services participated in this prospective study. Adherence to ocular hypotensive therapy was measured using an electronic dose monitor (Travatan Dosing Aid, Alcon Laboratories Inc., Fort Worth, TX) and collected data at 3 months after enrollment. We used 3 different definitions of adherence: 1) Definition 1: the proportion of days taking the prescribed number of drops within 3 hours of the prescribed dosing time; 2) Definition 2: the proportion of days taking any drops within 3 hours of the prescribed dosing time; and 3) Definition 3: the proportion of days taking any drops within 6 hours of the prescribed dosing time. Univariate and multivariate models were used to determine the association between the 3 adherence definitions, medical, demographic, socioeconomic, and ocular factors at 3-month follow-up. The main outcome measures for this study were risk factors for poor objective medication adherence. Adherence, using Definition 1, Definition 2, and Definition 3, was 64%, 75%, and 80%, respectively. Age, total number of other eye diseases, and race were significantly associated with full treatment adherence (Definition 1), with race alone significantly predicting 11% of full treatment adherence. For Definition 2, age, income, level of education, and total number of eye diseases were significantly associated with partial adherence (3 h), again race alone significantly predicted 15% of partial adherence (any drops within 3 h). For Definition 3, race, income, level of education, and total number of other eye diseases significantly predicted partial adherence (any drops within 6 h), both race and income predicted 19% of partial treatment adherence. Significant differences for adherence rates between patients of European descent and those of African descent were found for all 3 definitions with those who were less adherent more likely to be of African descent. Electronic dose monitors provide important information regarding adherence to topical ocular hypotensive medications in glaucoma patients. Electronic dose monitors show low adherence in a significant number of participants. Future studies are needed to determine the reasons for these differences in health behaviors related to glaucoma treatment, which should guide treatment of poor adherence with glaucoma therapy.

The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

PubMed

Cortes-Briones, Jose A; Cahill, John D; Skosnik, Patrick D; Mathalon, Daniel H; Williams, Ashley; Sewell, R Andrew; Roach, Brian J; Ford, Judith M; Ranganathan, Mohini; D'Souza, Deepak Cyril

2015-12-01

Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC. Published by Elsevier Inc.

Histological, molecular and biochemical detection of renal injury after Echis pyramidum snake envenomation in rats

PubMed Central

Al-Johany, Awadh M.; Al-Sadoon, Mohamed K.; Abdel Moneim, Ahmed E.; Bauomy, Amira A.; Diab, Marwa S.M.

2014-01-01

Nephrotoxicity is a common sign of snake envenomation. The present work aimed to clarify the effect of intraperitoneal injection of 1/8 LD50 and 1/4 LD50 doses of Echis pyramidum snake venom on the renal tissue of rats after 2, 4 and 6 h from envenomation. Histopathological examination showed intense dose and time dependent abnormalities, including swelling glomerulus and tubular necrosis and damage as well as signs of intertubular medullary hemorrhage at early stages of envenomation. However, at late stages of envenomation by any of the doses under investigation, no intact renal corpuscles were recorded and complete lysis in renal corpuscles with ruptured Bowman’s capsules was observed. Immunohistochemistry by immunohistochemical staining was used to test the protein expression of Bax in renal tissue of rats. The result showed that the expression of Bax in renal tissue sections of envenomated rats was increased according to dose and time-dependant manner. The isolation of DNA from the renal cells of envenomed rats pointed out to the occurrence of DNA fragmentation, which is another indicator for renal tissue injury especially after 6 h of 1/4 LD50 of E. pyramidum envenomation. Oxidative stress biomarkers malondialdehyde and nitrite/nitrate levels, antioxidant parameters; glutathione, total antioxidant capacity and catalase were assayed in renal tissue homogenates. The venom induced significant increase in the levels of malondialdehyde and nitrite/nitrate while the levels of glutathione, total antioxidant capacity and catalase were significantly decreased, especially after 6 h of envenomation. The results revealed that the E. pyramidum induced dose and time-dependant significant disturbances in the physiological parameters in the kidney. We conclude that the use of the immunohistochemical techniques, the detection of DNA integrity and oxidative stress marker estimations are more specific tools that can clarify cellular injury and could point out to the defense activity of the renal tissue at envenomation. PMID:25972751

Histological, molecular and biochemical detection of renal injury after Echis pyramidum snake envenomation in rats.

PubMed

Al-Johany, Awadh M; Al-Sadoon, Mohamed K; Abdel Moneim, Ahmed E; Bauomy, Amira A; Diab, Marwa S M

2015-05-01

Nephrotoxicity is a common sign of snake envenomation. The present work aimed to clarify the effect of intraperitoneal injection of 1/8 LD50 and 1/4 LD50 doses of Echis pyramidum snake venom on the renal tissue of rats after 2, 4 and 6 h from envenomation. Histopathological examination showed intense dose and time dependent abnormalities, including swelling glomerulus and tubular necrosis and damage as well as signs of intertubular medullary hemorrhage at early stages of envenomation. However, at late stages of envenomation by any of the doses under investigation, no intact renal corpuscles were recorded and complete lysis in renal corpuscles with ruptured Bowman's capsules was observed. Immunohistochemistry by immunohistochemical staining was used to test the protein expression of Bax in renal tissue of rats. The result showed that the expression of Bax in renal tissue sections of envenomated rats was increased according to dose and time-dependant manner. The isolation of DNA from the renal cells of envenomed rats pointed out to the occurrence of DNA fragmentation, which is another indicator for renal tissue injury especially after 6 h of 1/4 LD50 of E. pyramidum envenomation. Oxidative stress biomarkers malondialdehyde and nitrite/nitrate levels, antioxidant parameters; glutathione, total antioxidant capacity and catalase were assayed in renal tissue homogenates. The venom induced significant increase in the levels of malondialdehyde and nitrite/nitrate while the levels of glutathione, total antioxidant capacity and catalase were significantly decreased, especially after 6 h of envenomation. The results revealed that the E. pyramidum induced dose and time-dependant significant disturbances in the physiological parameters in the kidney. We conclude that the use of the immunohistochemical techniques, the detection of DNA integrity and oxidative stress marker estimations are more specific tools that can clarify cellular injury and could point out to the defense activity of the renal tissue at envenomation.

The Association between Tobacco Smoke and Serum Immunoglobulin E Levels in Korean Adults.

PubMed

Kim, Young Soo; Kim, Hee Yeon; Ahn, Hyo-Suk; Sohn, Tae Seo; Song, Jae Yen; Lee, Young Bok; Lee, Dong-Hee; Lee, Jae-Im; Jeong, Seong Cheol; Chae, Hiun Suk; Han, Kyungdo; Yeo, Chang Dong

2017-10-01

Objective Smoking is common in patients with allergic diseases. The aim of this study was to evaluate the cross-sectional association between the current smoking status and total and specific Immunoglobulin E (IgE) levels in Korean adults. Methods Data were obtained from the 2010 Korean National Health and Nutrition Examination Survey, a national cross-sectional study. We analyzed the data of subjects whose smoking status and serum IgE levels were of acceptable quality. Results A total of 1,963 subjects (1,118 never smokers, 340 ex-smokers, and 505 current smokers) were included. The total IgE levels and specific IgE levels to house dust mite Dermatophagoides farinae (Df), cockroach, and dog allergens in never smokers were significantly (p<0.0001) lower than in ex-smokers or current smokers. After adjusting for other variables, current smokers independently had significantly higher levels of total IgE and cockroach-specific IgE than ex-smokers or never smokers. The proportions of subjects with total IgE ≥150 kU/L and specific IgE ≥0.35 kU/L to Df-specific IgE were significantly (p value for trend <0.05) increased in ex-smokers and current smokers. The total IgE levels and IgE levels specific to Df, cockroaches, and dogs significantly (p value for trend <0.05) and proportionally increased with increasing numbers of cigarettes smoked daily. Conclusion Smoking was associated with elevated total IgE levels and IgE levels specific to Df, cockroach, and dog allergens in a cumulative, dose-dependent manner. Furthermore, current smoking status was an independent risk factor for elevated total IgE levels and IgE levels specific to cockroach allergen.

A lead isotope distribution study in swine tissue using ICP-MS

USGS Publications Warehouse

May, T.W.; Wiedmeyer, Ray H.; Brown, L.D.; Casteel, S.W.

1999-01-01

In the United States lead is an ubiquitous environmental pollutant that is a serious human health hazard, especially for women of childbearing age, developing fetuses, and young children. Information concerning the uptake and distribution of lead to maternal and fetal tissues during pregnancy is poorly documented. A study was designed using domestic swine and lead isotope enrichment methodology to focus on maternal absorption and distribution of lead into bone and soft tissues, including the fetal compartment, under varying conditions of oral lead exposure and during altered physiological states (pregnant vs unbred). Total lead levels and Pb207/Pb206 ratios in bone (femur and vertebra), blood, and soft tissues (liver, kidney, brain) were determined by ICP-MS. Lead in fetal tissues derived from maternal bone could be differentiated from that derived from exogenous dosing. Unbred swine absorbed much less lead than pregnant females receiving the same dose. The accuracy and precision of ICP-MS at the instrumental level and for the entire method (sample collection, digestion, and analysis) were evaluated for both Pb207/Pb206 ratios and total lead. Several changes were suggested in method design to improve both instrumental and total method precision.

Six months exposure to a real life mixture of 13 chemicals' below individual NOAELs induced non monotonic sex-dependent biochemical and redox status changes in rats.

PubMed

Docea, Anca Oana; Gofita, Eliza; Goumenou, Marina; Calina, Daniela; Rogoveanu, Otilia; Varut, Marius; Olaru, Cristian; Kerasioti, Efthalia; Fountoucidou, Polyxeni; Taitzoglou, Ioannis; Zlatian, Ovidiu; Rakitskii, Valerii N; Hernandez, Antonio F; Kouretas, Dimitrios; Tsatsakis, Aristidis

2018-05-01

This study assessed the potential adverse health effects of long-term low-dose exposure to chemical mixtures simulating complex real-life human exposures. Four groups of Sprague Dawley rats were administered mixtures containing carbaryl, dimethoate, glyphosate, methomyl, methyl parathion, triadimefon, aspartame, sodium benzoate, calcium disodium ethylene diamine tetra-acetate, ethylparaben, butylparaben, bisphenol A, and acacia gum at doses of 0, 0.25, 1 or 5 times the respective Toxicological Reference Values (TRV): acceptable daily intake (ADI) or tolerable daily intake (TDI) in a 24 weeks toxicity study. Body weight gain, feed and water consumption were evaluated weekly. At 24 weeks blood was collected and biochemistry parameters and redox status markers were assessed. Adverse effects were observed on body weight gain and in hepatotoxic parameters such as the total bilirubin, alanine aminotransferase (ALT) and alkaline phosphatase (ALP), especially in low dose and affecting mainly male rats. The low dose group showed increased catalase activity both in females and males, whereas the high dose group exhibited decreased protein carbonyl and total antioxidant capacity (TAC) levels in both sex groups. Non-monotonic effects and adaptive responses on liver function tests and redox status, leading to non-linear dose-responses curves, are probably produced by modulation of different mechanisms. Copyright © 2018. Published by Elsevier Ltd.

Estimation of neutron dose equivalent at the mezzanine of the Advanced Light Source and the laboratory boundary using the ORNL program MORSE.

PubMed

Sun, R K

1990-12-01

To investigate the radiation effect of neutrons near the Advanced Light Source (ALS) at Lawrence Berkeley Laboratory (LBL) with respect to the neutron dose equivalents in nearby occupied areas and at the site boundary, the neutron transport code MORSE, from Oak Ridge National Laboratory (ORNL), was used. These dose equivalents result from both skyshine neutrons transported by air scattering and direct neutrons penetrating the shielding. The ALS neutron sources are a 50-MeV linear accelerator and its transfer line, a 1.5-GeV booster, a beam extraction line, and a 1.9-GeV storage ring. The most conservative total occupational-dose-equivalent rate in the center of the ALS mezzanine, 39 m from the ALS center, was found to be 1.14 X 10(-3) Sv y-1 per 2000-h "occupational" year, and the total environmental-dose-equivalent rate at the ALS boundary, 125 m from the ALS center, was found to be 3.02 X 10(-4) Sv y-1 per 8760-h calendar year. More realistic dose-equivalent rates, using the nominal (expected) storage-ring current, were calculated to be 1.0 X 10(-4) Sv y-1 and 2.65 X 10(-5) Sv y-1 occupational year and calendar year, respectively, which are much lower than the DOE reporting levels.

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

PubMed

Wilson, R E; Hoey, B; Margison, G P

1993-04-01

The effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.

Benchmark Dose Modeling Estimates of the Concentrations of Inorganic Arsenic That Induce Changes to the Neonatal Transcriptome, Proteome, and Epigenome in a Pregnancy Cohort.

PubMed

Rager, Julia E; Auerbach, Scott S; Chappell, Grace A; Martin, Elizabeth; Thompson, Chad M; Fry, Rebecca C

2017-10-16

Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling. Genome-wide DNA methylation, microRNA expression, mRNA expression, and protein expression levels in cord blood were modeled against total urinary arsenic (U-tAs) levels from pregnant women exposed to varying levels of iAs. Dose-response relationships were modeled in BMDExpress, and BMDs representing 10% response levels were estimated. Overall, DNA methylation changes were estimated to occur at lower exposure concentrations in comparison to other molecular endpoints. Multi-omic module eigengenes were derived through weighted gene co-expression network analysis, representing co-modulated signatures across transcriptomic, proteomic, and epigenomic profiles. One module eigengene was associated with decreased gestational age occurring alongside increased iAs exposure. Genes/proteins within this module eigengene showed enrichment for organismal development, including potassium voltage-gated channel subfamily Q member 1 (KCNQ1), an imprinted gene showing differential methylation and expression in response to iAs. Modeling of this prioritized multi-omic module eigengene resulted in a BMD(BMDL) of 58(45) μg/L U-tAs, which was estimated to correspond to drinking water arsenic concentrations of 51(40) μg/L. Results are in line with epidemiological evidence supporting effects of prenatal iAs occurring at levels <100 μg As/L urine. Together, findings present a variety of BMD measures to estimate doses at which prenatal iAs exposure influences neonatal outcome-relevant transcriptomic, proteomic, and epigenomic profiles.

Dose and Duration of Opioid Use in Patients with Cancer and Noncancer Pain at an Outpatient Hospital Setting in Malaysia.

PubMed

Zin, Che S; Rahman, Norny A; Ismail, Che R; Choy, Leong W

2017-07-01

There are currently limited data available on the patterns of opioid prescribing in Malaysia. This study investigated the patterns of opioid prescribing and characterized the dosing and duration of opioid use in patients with noncancer and cancer pain. This retrospective, cross-sectional study was conducted at an outpatient hospital setting in Malaysia. All prescriptions for opioids (dihydrocodeine, fentanyl, morphine, and oxycodone) issued between January 2013 and December 2014 were examined. The number of prescriptions and patients, the distribution of mean daily dose, annual total days covered with opioids, and annual total opioid dose at the individual level were calculated and stratified by noncancer and cancer groups. A total of 1015 opioid prescriptions were prescribed for 347 patients from 2013 to 2014. Approximately 41.5% of patients (N = 144/347) and 58.5% (N = 203/347) were associated with noncancer and cancer diagnosis, respectively. Oxycodone (38.0%) was the highest prescribed primarily for the noncancer group. The majority of patients in both noncancer (74.3%) and cancer (60.4%) groups were receiving mean daily doses of < 50 mg morphine equivalents. The chronic use of opioids (> 90 days per year) was associated with 21.8% of patients in the noncancer group and 17.5% in the cancer group. The finding from this study showed that 41.5% of opioid users at an outpatient hospital setting in Malaysia received opioids for noncancer pain and 21.8% of these users were using opioids for longer than 90 days. The average daily dose in the majority of patients in both groups of noncancer and cancer was modest. © 2016 World Institute of Pain.

Effects of crude kerosene on testosterone levels, aggression and toxicity in rat.

PubMed

Njoroge, Rachel W; Macharia, Benson N; Sawe, Dinah J; Maiyoh, Geoffrey K

2015-01-01

The use of crude kerosene as a dietary supplement in boarding schools has been a common practice in east Africa and other countries for many years, with the belief of it reducing the sex drive (libido) at the pubertal stage. There is however no scientific basis for this belief. The present study aimed at using a rat animal model to investigate the effects of crude kerosene on serum testosterone levels, aggression and its possible toxic effects. Fifteen male albino rats of approximately similar age and average weights were put into three groups of five animals each; the control group (placebo), low kerosene dose (10 μl/day) group and high kerosene dose (300 μl/day) group. ELISA was used to determine the serum testosterone levels. During treatment, changes in aggression were observed and noted. Liver toxicity was determined using enzyme assays, total protein and albumin while renal toxicity was monitored using serum creatinine levels. A full hemogram was conducted to determine hematological effects. Various tissue biopsies were obtained and examined using histopathological techniques for evidence of toxicity. Contrary to the common belief, our findings showed an overall increase of serum testosterone levels of up to 66% in the low dose and 75% in the high dose groups, with an increasing trend by the end of the study. The high dose group showed significantly increased levels of white blood cells (WBC) ( p  = 0.036), red blood cells (RBC) ( p  = 0.025), hematocrit (HCT) ( p  = 0.03), red cell distribution width ( p  = 0.028) and platelets ( p  = 0.017). The histological results of the stomach indicated chronic gastritis.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

PubMed

Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

2013-01-01

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Comparison of low-dose spinal anesthesia and single-shot femoral block combination with conventional dose spinal anesthesia in outpatient arthroscopic meniscus repair.

PubMed

Turhan, K S Cakar; Akmese, R; Ozkan, F; Okten, F F

2015-04-01

In the current prospective, randomized study, we aimed to compare the effects of low dose selective spinal anesthesia with 5 mg of hyperbaric bupivacaine and single-shot femoral nerve block combination with conventional dose selective spinal anesthesia in terms of intraoperative anesthesia characteristics, block recovery characteristics, and postoperative analgesic consumption. After obtaining institutional Ethics Committee approval, 52 ASA I-II patients aged 25-65, undergoing arthroscopic meniscus repair were randomly assigned to Group S (conventional dose selective spinal anesthesia with 10 mg bupivacaine) and Group FS (low-dose selective spinal anesthesia with 5mg bupivacaine +single-shot femoral block with 0.25% bupivacaine). Primary endpoints were time to reach T12 sensory block level, L2 regression, and complete motor block regression. Secondary endpoints were maximum sensory block level (MSBL); time to reach MSBL, time to first urination, time to first analgesic consumption and pain severity at the time of first mobilization. Demographic characteristics were similar in both groups (p > 0.05). MSBL and time to reach T12 sensory level were similar in both groups (p > 0.05). Time to reach L2 regression, complete motor block regression, and time to first micturition were significantly shorter; time to first analgesic consumption was significantly longer; and total analgesic consumption and severity of pain at time of first mobilization were significantly lower in Group FS (p < 0.05). The findings of the current study suggest that addition of single-shot femoral block to low dose spinal anesthesia could be an alternative to conventional dose spinal anesthesia in outpatient arthroscopic meniscus repair. NCT02322372.

GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation

PubMed Central

Li, Shuang; Zhang, Qing-Zhao; Zhang, De-Qin; Feng, Jiang-Bin; Luo, Qun; Lu, Xue; Wang, Xin-Ru; Li, Kun-Peng; Chen, De-Qing; Mu, Xiao-Feng; Gao, Ling; Liu, Qing-Jie

2017-01-01

The identification of rapid, sensitive and high-throughput biomarkers is imperative in order to identify individuals harmed by radiation accidents, and accurately evaluate the absorbed doses of radiation. DNA microarrays have previously been used to evaluate the alterations in growth/differentiation factor 15 (GDF15) gene expression in AHH-1 human lymphoblastoid cells, following exposure to γ-rays. The present study aimed to characterize the relationship between the dose of ionizing radiation and the produced effects in GDF-15 gene expression in AHH-1 cells and human peripheral blood lymphocytes (HPBLs). GDF-15 mRNA and protein expression levels following exposure to γ-rays and neutron radiation were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis in AHH-1 cells. In addition, alterations in GDF-15 gene expression in HPBLs following ex vivo irradiation were evaluated. The present results demonstrated that GDF-15 mRNA and protein expression levels in AHH-1 cells were significantly upregulated following exposure to γ-ray doses ranging between 1 and 10 Gy, regardless of the dose rate. A total of 48 h following exposure to neutron radiation, a dose-response relationship was identified in AHH-1 cells at γ-ray doses between 0.4 and 1.6 Gy. GDF-15 mRNA levels in HPBLs were significantly upregulated following exposure to γ-ray doses between 1 and 8 Gy, within 4–48 h following irradiation. These results suggested that significant time- and dose-dependent alterations in GDF-15 mRNA and protein expression occur in AHH-1 cells and HPBLs in the early phases following exposure to ionizing radiation. In conclusion, alterations in GDF-15 gene expression may have potential as a biomarker to evaluate radiation exposure. PMID:28440431

Direct measurement of a patient's entrance skin dose during pediatric cardiac catheterization

PubMed Central

Sun, Lue; Mizuno, Yusuke; Iwamoto, Mari; Goto, Takahisa; Koguchi, Yasuhiro; Miyamoto, Yuka; Tsuboi, Koji; Chida, Koichi; Moritake, Takashi

2014-01-01

Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose–area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 ± 59 (mean ± standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed. PMID:24968708

Dose-dependent cytotoxicity evaluation of graphite nanoparticles for diamond-like carbon film application on artificial joints.

PubMed

Liao, T T; Deng, Q Y; Wu, B J; Li, S S; Li, X; Wu, J; Leng, Y X; Guo, Y B; Huang, N

2017-01-24

While a diamond-like carbon (DLC)-coated joint prosthesis represents the implant of choice for total hip replacement in patients, it also leads to concern due to the cytotoxicity of wear debris in the form of graphite nanoparticles (GNs), ultimately limiting its clinical use. In this study, the cytotoxicity of various GN doses was evaluated. Mouse macrophages and osteoblasts were incubated with GNs (<30 nm diameter), followed by evaluation of cytotoxicity by means of assessing inflammatory cytokines, results of alkaline phosphatase assays, and related signaling protein expression. Cytotoxicity evaluation showed that cell viability decreased in a dose-dependent manner (10-100 μg ml -1 ), and steeply declined at GNs concentrations greater than 30 μg ml -1 . Noticeable cytotoxicity was observed as the GN dose exceeded this threshold due to upregulated receptor of activator of nuclear factor kB-ligand expression and downregulated osteoprotegerin expression. Meanwhile, activated macrophage morphology was observed as a result of the intense inflammatory response caused by the high doses of GNs (>30 μg ml -1 ), as observed by the increased release of TNF-α and IL-6. The results suggest that GNs had a significant dose-dependent cytotoxicity in vitro, with a lethal dose of 30 μg ml -1 leading to dramatic increases in cytotoxicity. Our GN cytotoxicity evaluation indicates a safe level for wear debris-related arthropathy and could propel the clinical application of DLC-coated total hip prostheses.

Assessment of national dosimetry quality audits results for teletherapy machines from 1989 to 2015.

PubMed

Muhammad, Wazir; Ullah, Asad; Mahmood, Khalid; Matiullah

2016-01-01

The purpose of this study was to ensure accuracy in radiation dose delivery, external dosimetry quality audit has an equal importance with routine dosimetry performed at clinics. To do so, dosimetry quality audit was organized by the Secondary Standard Dosimetry Laboratory (SSDL) of Pakistan Institute of Nuclear Science and Technology (PINSTECH) at the national level to investigate and minimize uncertainties involved in the measurement of absorbed dose, and to improve the accuracy of dose measurement at different radiotherapy hospitals. A total of 181 dosimetry quality audits (i.e., 102 of Co-60 and 79 of linear accelerators) for teletherapy units installed at 22 different sites were performed from 1989 to 2015. The percent deviation between users’ calculated/stated dose and evaluated dose (in the result of on-site dosimetry visits) were calculated and the results were analyzed with respect to the limits of ± 2.5% (ICRU "optimal model") ± 3.0% (IAEA on-site dosimetry visits limit) and ± 5.0% (ICRU minimal or "lowest acceptable" model). The results showed that out of 181 total on-site dosimetry visits, 20.44%, 16.02%, and 4.42% were out of acceptable limits of ± 2.5% ± 3.0%, and ± 5.0%, respectively. The importance of a proper ongoing quality assurance program, recommendations of the followed protocols, and properly calibrated thermometers, pressure gauges, and humidity meters at radiotherapy hospitals are essential in maintaining consistency and uniformity of absorbed dose measurements for precision in dose delivery.

Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

PubMed

Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

2012-04-10

Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

Pharmacokinetics, tissue distribution and metabolism of acriflavine and proflavine in the channel catfish (Ictalurus punctatus).

PubMed

Plakas, S M; el Said, K R; Bencsath, F A; Musser, S M; Hayton, W L

1998-06-01

1. The disposition of proflavine (PRO) and acriflavine (ACR) were examined in channel catfish after intravascular (i.v.) dosing (1 mg/kg) or waterborne exposure (10 mg/l for 4 h). 2. After i.v. dosing, plasma concentration-time profiles of parent PRO and ACR were best described by two- and three-compartment pharmacokinetic models respectively. Terminal elimination half-lives of PRO and ACR in plasma were 8.7 and 11.4 h respectively. 3. In animals dosed with 14C-PRO or 14C-ACR, total drug equivalent concentrations were highest in the excretory organs and lowest in muscle, fat and plasma. In PRO-dosed animals, residues in the liver and trunk kidney were composed primarily of glucuronosyl and acetyl conjugates of PRO; residues in muscle were composed mostly (> 95%) of the parent drug. In ACR-dosed animals, the parent compound comprised > 90% of the total residues in all tissues examined. 4. PRO and ACR were poorly absorbed in catfish during waterborne exposure. At the end of a 4-h exposure, parent PRO and ACR concentrations in muscle were 0.064 and 0.020 microgram/g respectively. Levels in muscle declined below the limit of determination (0.005 microgram/g) within 1-2 weeks.

Effect of continuous gamma-ray exposure on performance of learned tasks and effect of subsequent fractionated exposures on blood-forming tissue

NASA Technical Reports Server (NTRS)

Spalding, J. F.; Holland, L. M.; Prine, J. R.; Farrer, D. N.; Braun, R. G.

1972-01-01

Sixteen monkeys trained to perform continuous and discrete-avoidance and fixed-ratio tasks with visual and auditory cues were performance-tested before, during, and after 10-day gamma-ray exposures totaling 0, 500, 750, and 1000 rads. Approximately 14 months after the performance-test exposures, surviving animals were exposed to 100-rad gamma-ray fractions at 56-day intervals to observe injury and recovery patterns of blood-forming tissues. The fixed-ratio, food-reward task performance showed a transient decline in all dose groups within 24 hours of the start of gamma-ray exposure, followed by recovery to normal food-consumption levels within 48 to 72 hours. Avoidance tasks were performed successfully by all groups during the 10-day exposure, but reaction times of the two higher dose-rate groups in which animals received 3 and 4 rads per hour or total doses of 750 and 1000 rads, respectively, were somewhat slower.

High-Dose Selenium for the Mitigation of Radiation Injury: A Pilot Study in a Rat Model

PubMed Central

Sieber, Fritz; Muir, Sarah A.; Cohen, Eric P.; North, Paula E.; Fish, Brian L.; Irving, Amy A.; Mäder, Marylou; Moulder, John E.

2009-01-01

The purpose of this study was to evaluate in an animal model the safety and efficacy of dietary supplementation with high doses of selenium for the mitigation of the type of radiation injury that might be sustained during a nuclear accident or an act of radiological terrorism. Age-matched male rats were exposed to 10 Gy (single dose) of total-body irradiation (TBI) followed by a syngeneic bone marrow transplant, then randomized to standard drinking water or drinking water supplemented with sodium selenite or seleno-L-methionine. At 21 weeks after TBI, most rats on standard drinking water had severe renal failure with a mean blood urea nitrogen (BUN) level of 124 ± 29 mg/dl (geometric mean ± SE) whereas rats on selenium-supplemented drinking water (100 μg/day) had a mean BUN level of 67 ± 12 mg/dl. The mitigating effect of selenium was confirmed by histopathological analyses. None of the animals on high-dose selenium showed signs of selenium toxicity. Our results suggest that dietary supplementation with high-dose selenium may provide a safe, effective and practical way to mitigate radiation injury to kidneys. PMID:19267564

Characterization and recovery of Deep Sub Micron (DSM) technologies behavior under radiation

NASA Technical Reports Server (NTRS)

Stoica, Adrian; Wang, Xiao

2005-01-01

This paper serves a twofold purpose: characterize the behavior of a reconfigurable chip exposed to radiation; and demonstrate a method for functionality recovery due to Total Ionizing Dose (TID) effects. The experiments are performed using a PL developed reconfigurable device, a Field Programmable Transistor Array (FPTA). The paper initially describes experiments on the characterization of the NMOS transistor behavior for TID values up to 300krad. The behavior of analog and digital circuits downloaded onto the FPTA chip is also assessed for TID effects. This paper also presents a novel approach for circuit functionality recovery due to radiation effects based on Evolvable Hardware. The key idea is to reconfigure a programmable device, in-situ, to compensate, or bypass its degraded or damaged components. Experiments with total radiation dose up to 300kRad show that while the functionality of a variety of circuits, including digital gates, a rectifier and a Digital to Analog Converter implemented on a FPTA-2 chip is degraded/lost at levels before 200kRad, the correct functionality can be recovered through the proposed evolutionary approach and the chips are able to survive higher radiation, for several functions in excess of total radiation dose of 250kRad.

Model-derived dose rates per unit concentration of radon in air in a generic plant geometry.

PubMed

Vives i Batlle, J; Smith, A; Vives-Lynch, S; Copplestone, D; Pröhl, G; Strand, T

2011-11-01

A model for the derivation of dose rates per unit radon concentration in plants was developed in line with the activities of a Task Group of the International Commission on Radiological Protection (ICRP), aimed at developing more realistic dosimetry for non-human biota. The model considers interception of the unattached and attached fractions of the airborne radon daughters by plant stomata, diffusion of radon gas through stomata, permeation through the plant's epidermis and translocation of deposited activity to plant interior. The endpoint of the model is the derivation of dose conversion coefficients relative to radon gas concentration at ground level. The model predicts that the main contributor to dose is deposition of (214)Po α-activity on the plant surface and that diffusion of radon daughters through the stomata is of relatively minor importance; hence, daily variations have a small effect on total dose.

Dose Assessment of Los Alamos National Laboratory-Derived Residual Radionuclides in Soils within Tract A-18-2 for Land Conveyance and Transfer Decisions

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

Ruedig, Elizabeth; Whicker, Jeffrey Jay

In 2017, soil sampling for radiological materials was conducted within Tract A-18-2 specifically for land conveyance decisions. Measurements of radionuclides in soil samples were evaluated against a recreational use scenario, and all measurements were below screening action levels for each radionuclide. The total estimated dose was less than 1 mrem/y (< 10 μSv/y) for a hypothetical recreational user (compared to a dose limit of 25 mrem/y (250 μSv/y)). Dose estimates were based on the 95% upper confidence limits for radionuclide concentrations within the Tract. Additionally, dose estimates less than 3 mrem/y are considered to be As Low As Reasonably Achievable,more » so no follow-up analysis was conducted. Release of this property is consistent with the requirements of DOE Order 458.1 and Policy 412.« less

A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men.

PubMed

Hair, W M; Kitteridge, K; O'Connor, D B; Wu, F C

2001-11-01

This study investigated the effect of transdermal T and oral desogestrel on the reproductive axis of healthy men. Twenty-three men were randomized to 1 of 3 treatment groups and received a daily transdermal T patch plus oral desogestrel at a dose of 75, 150, or 300 microg/d for 24 wk. Baseline blood and semen samples were obtained and then every 4 wk thereafter for 32 wk. The outcome measures were sperm density and plasma levels of FSH, LH, total and free T. The results show a dose-dependent suppression of spermatogenesis and gonadotropins. Seven of the 17 subjects became azoospermic. Desogestrel (300 microg daily) in combination with 5 mg daily transdermal T was the most effective (57% azoospermic), whereas a dose of 75 microg was ineffective (0% azoospermic). Total and free plasma T were reduced by approximately 30%. High density lipoprotein cholesterol was significantly reduced. No serious side-effects were encountered. We conclude that daily self-administered desogestrel with transdermal T is capable of suppressing the male reproductive axis, although the efficacy was less marked and less consistent than injectable regimens. The lower efficacy is likely to be due to failure of the transdermal T system to maintain circulating T levels consistently in the required range.

Efficacy Study of Novel Diamidine Compounds in a Trypanosoma evansi Goat Model

PubMed Central

Gillingwater, Kirsten; Gutierrez, Carlos; Bridges, Arlene; Wu, Huali; Deborggraeve, Stijn; Ali Ekangu, Rosine; Kumar, Arvind; Ismail, Mohamed; Boykin, David; Brun, Reto

2011-01-01

Three diamidines (DB 75, DB 867 and DB 1192) were selected and their ability to cure T. evansi experimentally infected goats was investigated. A toxicity assessment and pharmacokinetic analysis of these compounds were additionally carried out. Goats demonstrated no signs of acute toxicity, when treated with four doses of 1 mg/kg/day (total dose 4 mg/kg). Complete curative efficacy of experimentally infected goats was seen in the positive control group treated with diminazene at 5 mg/kg and in the DB 75 and DB 867 groups treated at 2.5 mg/kg. Drug treatment was administered once every second day for a total of seven days. Complete cure was also seen in the group of goats treated with DB 75 at 1.25 mg/kg. DB 1192 was incapable of curing goats at either four-times 2.5 mg/kg or 1.25 mg/kg. Pharmacokinetic analysis clearly demonstrated that the treatment failures of DB 1192 were due to sub-therapeutic compound levels in goat plasma, whilst compound levels for DB 75 and DB 867 remained well within the therapeutic window. In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection. PMID:21698106

Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model.

PubMed

Gillingwater, Kirsten; Gutierrez, Carlos; Bridges, Arlene; Wu, Huali; Deborggraeve, Stijn; Ekangu, Rosine Ali; Kumar, Arvind; Ismail, Mohamed; Boykin, David; Brun, Reto

2011-01-01

Three diamidines (DB 75, DB 867 and DB 1192) were selected and their ability to cure T. evansi experimentally infected goats was investigated. A toxicity assessment and pharmacokinetic analysis of these compounds were additionally carried out. Goats demonstrated no signs of acute toxicity, when treated with four doses of 1 mg/kg/day (total dose 4 mg/kg). Complete curative efficacy of experimentally infected goats was seen in the positive control group treated with diminazene at 5 mg/kg and in the DB 75 and DB 867 groups treated at 2.5 mg/kg. Drug treatment was administered once every second day for a total of seven days. Complete cure was also seen in the group of goats treated with DB 75 at 1.25 mg/kg. DB 1192 was incapable of curing goats at either four-times 2.5 mg/kg or 1.25 mg/kg. Pharmacokinetic analysis clearly demonstrated that the treatment failures of DB 1192 were due to sub-therapeutic compound levels in goat plasma, whilst compound levels for DB 75 and DB 867 remained well within the therapeutic window. In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection.

Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients.

PubMed

Provenzani, Alessio; Notarbartolo, Monica; Labbozzetta, Manuela; Poma, Paola; Vizzini, Giovanni; Salis, Paola; Caccamo, Chiara; Bertani, Tullio; Palazzo, Ugo; Polidori, Piera; Gridelli, Bruno; D'Alessandro, Natale

2011-12-01

Tacrolimus is a substrate of cytochrome P4503A (CYP3A) enzymes as well as of the drug transporter ABCB1. We have investigated the possible influence of CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) and other factors (e.g. albumin, hematocrit and steroids) on tacrolimus blood levels achieved in a population of Caucasian liver (n=51) and kidney (n=50) transplant recipients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were recorded and the weight-adjusted tacrolimus dosage (mg/kg/day) was calculated. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*1 and *3 [6986A>G] as well as ABCB1 at exons 21 [2677G>T/A] and 26 [3435C>T] in both liver transplant donors and recipients and in kidney transplant recipients. Of the 152 subjects studied, 84.9% showed a CYP3A5*3/*3 genotype. The total frequency of the allelic variant *3 was 93%. For the G2677T/A and C3435T polymorphisms the total frequencies of the allelic variants T/A and T were 44.7 and 46.7%, respectively. At 1, 3 and 6 months after transplantation the dose-adjusted C0 levels were significantly lower in patients with one copy of the *1 allele compared to those homozygous for the *3 allele. In the case of liver transplant patients the tacrolimus dose requirements were dominantly influenced by the polymorphisms of the CYP3A5 gene in the donors. With regard to the ABCB1 SNPs, in general they did not show any appreciable influence on tacrolimus dosing requirements; however, kidney transplant recipients carrying the 2677T/A allele required significantly higher daily tacrolimus doses than subjects homozygous for the wild-type allele. Identification of CYP3A5 single nucleotide polymorphisms prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus in the patients.

Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy

PubMed Central

NAKANO, KENJI; SATO, YASUYOSHI; TOSHIYASU, TAKASHI; SATO, YUKIKO; INAGAKI, LINA; TOMOMATSU, JUNICHI; SASAKI, TORU; SHIMBASHI, WATARU; FUKUSHIMA, HIROFUMI; YONEKAWA, HIROYUKI; MITANI, HIROKI; KAWABATA, KAZUYOSHI; TAKAHASHI, SHUNJI

2016-01-01

Although high-dose cisplatin is the standard regimen of concurrent chemoradiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (HNSCC), varying levels of patient tolerance towards cisplatin have been reported, and the predictive factors of cisplatin tolerance remain to be elucidated. The present study retrospectively reviewed newly diagnosed HNSCC patients who received CCRT. Cisplatin (80 mg/m2) was administered every 3 weeks. The proportion of high-dose cisplatin-tolerant patients (cumulative cisplatin dose, ≥200 mg/m2) was determined, and the predictive factors of cisplatin tolerance were analyzed in a logistic regression analysis. Between June 2006 and March 2013, a total of 159 patients were treated with CCRT. The median follow-up time was 36.7 months. A total of 73 patients (46%) tolerated a cumulative cisplatin dose ≥200 mg/m2; male gender [odds ratio (OR), 25.00; P=0.005] and high body surface area (BSA) (>1.80 m2; OR, 2.21; P=0.032) were significantly predictive of high-dose cisplatin tolerance. The high-dose cisplatin-tolerant patients had a significantly higher complete response (CR) rate (82 vs. 67%, P=0.045); however, there were no significant between-group differences in the 3-year OS (79.5 vs. 81.2%, P=0.59) or PFS (70.4 vs. 44.6%, P=0.076) by cisplatin tolerance. In clinical practice, approximately one-half of the patients tolerated high-dose cisplatin in CCRT. Male gender and high BSA could be predictive of cisplatin tolerance. PMID:26893880

Administration of low dose methamphetamine 12 h after a severe traumatic brain injury prevents neurological dysfunction and cognitive impairment in rats.

PubMed

Rau, Thomas F; Kothiwal, Aakriti S; Rova, Annela R; Brooks, Diane M; Rhoderick, Joseph F; Poulsen, Austin J; Hutchinson, Jim; Poulsen, David J

2014-03-01

We recently published data that showed low dose of methamphetamine is neuroprotective when delivered 3 h after a severe traumatic brain injury (TBI). In the current study, we further characterized the neuroprotective potential of methamphetamine by determining the lowest effective dose, maximum therapeutic window, pharmacokinetic profile and gene expression changes associated with treatment. Graded doses of methamphetamine were administered to rats beginning 8 h after severe TBI. We assessed neuroprotection based on neurological severity scores, foot fault assessments, cognitive performance in the Morris water maze, and histopathology. We defined 0.250 mg/kg/h as the lowest effective dose and treatment at 12 h as the therapeutic window following severe TBI. We examined gene expression changes following TBI and methamphetamine treatment to further define the potential molecular mechanisms of neuroprotection and determined that methamphetamine significantly reduced the expression of key pro-inflammatory signals. Pharmacokinetic analysis revealed that a 24-hour intravenous infusion of methamphetamine at a dose of 0.500 mg/kg/h produced a plasma Cmax value of 25.9 ng/ml and a total exposure of 544 ng/ml over a 32 hour time frame. This represents almost half the 24-hour total exposure predicted for a daily oral dose of 25mg in a 70 kg adult human. Thus, we have demonstrated that methamphetamine is neuroprotective when delivered up to 12 h after injury at doses that are compatible with current FDA approved levels. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

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

Robertson, John M., E-mail: jrobertson@beaumont.edu; Margolis, Jeffrey; Jury, Robert P.

2012-02-01

Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m{sup 2}) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additionalmore » 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.« less

Optimized image acquisition for breast tomosynthesis in projection and reconstruction space.

PubMed

Chawla, Amarpreet S; Lo, Joseph Y; Baker, Jay A; Samei, Ehsan

2009-11-01

Breast tomosynthesis has been an exciting new development in the field of breast imaging. While the diagnostic improvement via tomosynthesis is notable, the full potential of tomosynthesis has not yet been realized. This may be attributed to the dependency of the diagnostic quality of tomosynthesis on multiple variables, each of which needs to be optimized. Those include dose, number of angular projections, and the total angular span of those projections. In this study, the authors investigated the effects of these acquisition parameters on the overall diagnostic image quality of breast tomosynthesis in both the projection and reconstruction space. Five mastectomy specimens were imaged using a prototype tomosynthesis system. 25 angular projections of each specimen were acquired at 6.2 times typical single-view clinical dose level. Images at lower dose levels were then simulated using a noise modification routine. Each projection image was supplemented with 84 simulated 3 mm 3D lesions embedded at the center of 84 nonoverlapping ROIs. The projection images were then reconstructed using a filtered backprojection algorithm at different combinations of acquisition parameters to investigate which of the many possible combinations maximizes the performance. Performance was evaluated in terms of a Laguerre-Gauss channelized Hotelling observer model-based measure of lesion detectability. The analysis was also performed without reconstruction by combining the model results from projection images using Bayesian decision fusion algorithm. The effect of acquisition parameters on projection images and reconstructed slices were then compared to derive an optimization rule for tomosynthesis. The results indicated that projection images yield comparable but higher performance than reconstructed images. Both modes, however, offered similar trends: Performance improved with an increase in the total acquisition dose level and the angular span. Using a constant dose level and angular span, the performance rolled off beyond a certain number of projections, indicating that simply increasing the number of projections in tomosynthesis may not necessarily improve its performance. The best performance for both projection images and tomosynthesis slices was obtained for 15-17 projections spanning an angular are of approximately 45 degrees--the maximum tested in our study, and for an acquisition dose equal to single-view mammography. The optimization framework developed in this framework is applicable to other reconstruction techniques and other multiprojection systems.

Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure.

PubMed

Maier, Joscha; Sawall, Stefan; Kachelrieß, Marc

2014-05-01

Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levels from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the HDTV algorithm shows the best performance. At 50 mGy, the deviation from the reference obtained at 500 mGy were less than 4%. Also the LDPC algorithm provides reasonable results with deviation less than 10% at 50 mGy while PCF and MKB reconstruction show larger deviations even at higher dose levels. LDPC and HDTV increase CNR and allow for quantitative evaluations even at dose levels as low as 50 mGy. The left ventricular volumes exemplarily illustrate that cardiac parameters can be accurately estimated at lowest dose levels if sophisticated algorithms are used. This allows to reduce dose by a factor of 10 compared to today's gold standard and opens new options for longitudinal studies of the heart.

The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

PubMed Central

Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

2017-01-01

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p < 0.001). The egg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (p = 0.0062). Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (p = 0.036) but not at 5 (p > 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p < 0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (p > 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

NASA Technical Reports Server (NTRS)

Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

1989-01-01

The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

PubMed

Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2002-02-21

Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial.

PubMed

Bunnapradist, S; Ciechanowski, K; West-Thielke, P; Mulgaonkar, S; Rostaing, L; Vasudev, B; Budde, K

2013-03-01

Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4-15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Individual dose reconstruction among residents living in the vicinity of the Semipalatinsk nuclear test site using EPR spectroscopy of tooth enamel.

PubMed

Ivannikov, A I; Zhumadilov, Zh; Gusev, B I; Miyazawa, Ch; Jiao, L; Skvortsov, V G; Stepanenko, V F; Takada, J; Hoshi, M

2002-08-01

Individual accumulated doses were determined by EPR spectroscopy of tooth enamel for 26 adult persons residing in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The absorbed dose values due to radiation from nuclear tests were obtained after subtracting the contribution of natural background radiation from the total accumulated dose. The determined dose values ranged up to 250 mGy, except for one person from Semipalatinsk city with a measured dose of 2.8 +/- 0.4 Gy. Increased dose values were determined for the individuals whose teeth were formed before 1962, the end of the atmospheric nuclear tests. These values were found to be significantly larger than those obtained for a group of younger residents of heavily exposed territories and the residents of territories not exposed to radioactive fallout. These increased dose values are consistent with those based on officially registered data for the Northeastern part of Kazakstan adjacent to SNTS, which was exposed to high levels of radioactive fallout from nuclear tests in period 1949-1962.

Dose/Exposure‐Response Modeling to Support Dosing Recommendation for Phase III Development of Baricitinib in Patients with Rheumatoid Arthritis

PubMed Central

Chua, Laiyi; Ernest, Charles; Macias, William; Rooney, Terence; Tham, Lai San

2017-01-01

Baricitinib is an oral inhibitor of Janus kinases (JAKs), selective for JAK1 and 2. It demonstrated dose‐dependent efficacy in patients with moderate‐to‐severe rheumatoid arthritis (RA) in a phase IIb study up to 24 weeks. Population pharmacokinetic/pharmacodynamic (PopPK/PD) models were developed to characterize concentration‐time profiles and dose/exposure‐response (D/E‐R) relationships for the key efficacy (proportion of patients achieving American College of Rheumatology 20%, 50%, or 70% response rate) and safety endpoints (incidence of anemia) for the phase IIb study. The modeling suggested that 4 mg q.d. was likely to offer the optimum risk/benefit balance, whereas 2 mg q.d. had the potential for adequate efficacy. In addition, at the same total daily dose, a twice‐daily regimen is not expected to provide an advantage over q.d. dosing for the efficacy or safety endpoints. The model‐based simulations formed the rationale for key aspects of dosing, such as dose levels and dosing frequency for phase III development. PMID:28891251

Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice

PubMed Central

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

2010-01-01

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7–9, 10–12 or 13–15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13–15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug. PMID:23961116

Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

PubMed

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

2011-04-01

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

Opioid Rotation in Cancer Pain Treatment.

PubMed

Schuster, Michael; Bayer, Oliver; Heid, Florian; Laufenberg-Feldmann, Rita

2018-03-02

Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it. This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancerrelated pain who are regularly taking WHO level III opioids by the oral or trans - dermal route. 9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, bupre - norphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best. Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.

Low-dose dialysis combined with low protein intake can maintain nitrogen balance in peritoneal dialysis patients in poor economies
.

PubMed

Su, Chun-Yan; Wang, Tao; Lu, Xin-Hong; Ma, Sha; Tang, Wen; Wang, Pei-Yu

2017-02-01

Due to limited economic conditions, we tried to provide "fitted" dialysis doses instead of the doses recommended by the international guidelines to the individual patients. In the present cross-sectional study, we studied the dialysis adequacy and nutritional status of 5 peritoneal dialysis patients who had a low dialysis dose (2 bags, 4,000 mL/day). The 3-day dietary records were reviewed to calculate patients' energy, protein, and nitrogen intake (NI). The nitrogen removal (NR) from urine and dialysate was measured by Kjeldahl technique. Fecal nitrogen was estimated as 0.0155 g/kg/day. Subjective global nutritional assessment was used to evaluate the nutritional status. Among the 5 patients, 1 male and 4 female, mean age was 59 (42 - 81) years, dialysis duration 43 (33 - 74) months, body weight 51.05 ± 2.53 kg. The mean dietary protein intake was 0.66 g/kg/day, total weekly Kt/v was 1.25 (residual kidney Kt/v was 0.09), and total daily fluid removal was 699 mL. However, they achieved lower-level neutral nitrogen balance (NI 5.26 ± 0.93 g/day vs. NR 5.33 ± 0.81 g/day, N balance -0.07 ± 0.60 g/day). All of them maintained good nutritional status (SGA "A") without symptoms of nitrogen retention (serum urea 22 ± 4.18 mmol/L). Lower dialysis dose with lower daily protein intake can achieve a lower-level nitrogen balance and does not lead to malnutrition. It may be an effective approach to solve the dialysis problem for the economically week population in China, especially for people with a smaller body size with lower transport membrane.
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Parental knowledge of paediatric vaccination

PubMed Central

Borràs, Eva; Domínguez, Àngela; Fuentes, Miriam; Batalla, Joan; Cardeñosa, Neus; Plasencia, Antoni

2009-01-01

Background Although routine vaccination is a major tool in the primary prevention of some infectious diseases, there is some reluctance in a proportion of the population. Negative parental perceptions of vaccination are an important barrier to paediatric vaccination. The aim of this study was to investigate parental knowledge of paediatric vaccines and vaccination in Catalonia. Methods A retrospective, cross-sectional study was carried out in children aged < 3 years recruited by random sampling from municipal districts of all health regions of Catalonia. The total sample was 630 children. Parents completed a standard questionnaire for each child, which included vaccination coverage and knowledge about vaccination. The level of knowledge of vaccination was scored according to parental answers. Results An association was observed between greater vaccination coverage of the 4:4:4:3:1 schedule (defined as: 4 DTPa/w doses, 4 Hib doses, 4 OPV doses, 3 MenC doses and 1 MMR dose) and maternal age >30 years (OR: 2.30; 95% CI: 1.20–4.43) and with a knowledge of vaccination score greater than the mean (OR: 0.45; 95% CI: 0.28–0.72). The score increased with maternal educational level and in parents of vaccinated children. A total of 20.47% of parents stated that vaccines could have undesirable consequences for their children. Of these, 23.26% had no specific information and 17.83% stated that vaccines can cause adverse reactions and the same percentage stated that vaccines cause allergies and asthma. Conclusion Higher vaccination coverage is associated with older maternal age and greater knowledge of vaccination. Vaccination coverage could be raised by improving information on vaccines and vaccination. PMID:19473498

Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?

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

Harriss-Phillips, Wendy M., E-mail: wharrphil@gmail.com; School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia; Bezak, Eva

Purpose: To simulate stereotactic ablative radiation therapy on hypoxic and well-oxygenated in silico tumors, incorporating probabilistic parameter distributions and linear-quadratic versus linear-quadratic-cubic methodology and the evaluation of optimal fractionation schemes using biological effective dose (BED{sub α/β=10} {sub or} {sub 3}) comparisons. Methods and Materials: A temporal tumor growth and radiation therapy algorithm simulated high-dose external beam radiation therapy using stochastic methods. Realistic biological proliferative cellular hierarchy and pO{sub 2} histograms were incorporated into the 10{sup 8}-cell tumor model, with randomized radiation therapy applied during continual cell proliferation and volume-based gradual tumor reoxygenation. Dose fractions ranged from 6-35 Gy, with predictive outcomes presentedmore » in terms of the total doses (converted to BED) required to eliminate all cells that could potentially regenerate the tumor. Results: Well-oxygenated tumor control BED{sub 10} outcomes were not significantly different for high-dose versus conventional radiation therapy (BED{sub 10}: 79-84 Gy; Equivalent Dose in 2 Gy fractions with α/β of 10: 66-70 Gy); however, total treatment times decreased from 7 down to 1-3 weeks. For hypoxic tumors, an additional 28 Gy (51 Gy BED{sub 10}) was required, with BED{sub 10} increasing with dose per fraction due to wasted dose in the final fraction. Fractions of 9 Gy compromised well for total treatment time and BED, with BED{sub 10}:BED{sub 3} of 84:176 Gy for oxic and 132:278 Gy for non-reoxygenating hypoxic tumors. Initial doses of 12 Gy followed by 6 Gy further increased the therapeutic ratio. When delivering ≥9 Gy per fraction, applying reoxygenation and/or linear-quadratic-cubic cell survival both affected tumor control doses by a significant 1-2 fractions. Conclusions: The complex temporal dynamics of tumor oxygenation combined with probabilistic cell kinetics in the modeling of radiation therapy requires sophisticated stochastic modeling to predict tumor cell kill. For stereotactic ablative radiation therapy, high doses in the first week followed by doses that are more moderate may be beneficial because a high percentage of hypoxic cells could be eradicated early while keeping the required BED{sub 10} relatively low and BED{sub 3} toxicity to tolerable levels.« less

Radon exposure assessment for underground workers: a case of Seoul Subway Police officers in Korea.

PubMed

Song, Myeong Han; Chang, Byung-Uck; Kim, Yongjae; Cho, Kun-Woo

2011-11-01

The objective of this study is the systematic and individual assessment of the annual effective dose due to inhaled radon for the Seoul Subway Police officers, Korea. The annual average radon concentrations were found to be in the range of 18.9-114 Bq·m(-3) in their workplaces. The total annual effective doses which may likely to be received on duty were assessed to be in the range of 0.41-1.64 mSv·y(-1). These were well below the recommended action level 10 mSv·y(-1) by ICRP. However, the effective doses were higher than subway station staff in Seoul, Korea.

Prostaglandin analogous and antioxidant activity mediated gastroprotective action of Tabernaemontana divaricata (L.) R. Br. flower methanolic extract against chemically induced gastric ulcers in rats.

PubMed

Ali Khan, Mohammed Safwan; Mat Jais, Abdul Manan; Afreen, Adiba

2013-01-01

The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses--125, 250, and 500 mg/kg--orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization--high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous.

Maximum dose rate is a determinant of hypothyroidism after 131I therapy of Graves' disease but the total thyroid absorbed dose is not.

PubMed

Krohn, Thomas; Hänscheid, Heribert; Müller, Berthold; Behrendt, Florian F; Heinzel, Alexander; Mottaghy, Felix M; Verburg, Frederik A

2014-11-01

The determinants of successful (131)I therapy of Graves' disease (GD) are unclear. To relate dosimetry parameters to outcome of therapy to identify significant determinants eu- and/or hypothyroidism after (131)I therapy in patients with GD. A retrospective study in which 206 Patients with GD treated in University Hospital between November 1999 and January 2011. All received (131)I therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Post-therapy dosimetric thyroid measurements were performed twice daily until discharge. From these measurements, thyroid (131)I half-life, the total thyroid absorbed dose, and the maximum dose rate after (131)I administration were calculated. In all, 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after (131)I therapy. In univariate analysis, nonhyperthyroid and hyperthyroid patients only differed by sex. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal (131)I half-life, and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (P < .001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.

[Effect of Jianpi Yangzheng Xiaozheng Recipe on Apoptosis and Autophagy of Subcutaneous Transplanted Tumor in Nude Mice: an Experimental Study on Mechanism].

PubMed

Wu, Jian; Liu, Shen-lin; Zhang, Xing-xing; Chen, Min; Zou, Xi

2015-09-01

To observe the effect of Jianpi Yangzheng Xiaozheng Recipe (JYXR) on the tumor inhibition rate of subcutaneous transplanted tumor gastric cancer cell line MGC-803 in BALB/c nude mice, and to study its molecular mechanism of apoptosis and autophagy. Gastric cancer cell line MGC-803 was subcutaneously inoculated to nude mice for preparing transplanted gastric cancer models. Totally 32 BALB/c nude mice were randomly divided into 4 groups according to random digit table, i.e., the negative control group, the positive control group, the high dose JYXR group, the low dose JYXR group, 8 in each group. Normal saline was administered to mice in the negative control group by gastrogavage. 5-fluorouracil (5-Fu) at 2. 5 mg/kg was administered to mice in the positive control group by gastrogavage. JYXR at 85 and 43 g/kg was administered to mice in the high dose JYXR group and the low dose JYXR group by gastrogavage, once per day for 10 successive days. The effect of JYXR on the tumor inhibition rate of subcutaneous transplanted tumor was observed. Effects of JYXR on gene expression levels of Bax, Bcl-2, Fas, Cyclin D1, Cyclin D2, and Cyclin D3 in transplanted tumor were observed by real-time PCR. Effects of JYXR on protein expression levels of Procaspase-3, Procaspase-8, Procaspase-9, cleaved-PARP, Beclin-1, and LC3B were detected using Western blot. (1) Compared with the negative control group, the tumor weight was obviously reduced in the rest three groups (P <0. 05). The tumor weight was higher in the high dose JYXR group and the low dose JYXR group than in the positive control group (P <0. 05). (2) Results of RT-PCR indicated that, compared with the negative control group, expression levels of Bax were up-regulated, but expression levels of Bcl-2, Cyclin D1, Cyclin D2, and Cyclin D3 were down-regulated in the positive control group and JYXR groups (P <0. 05). The expression level of Fas was up-regulated in the positive control group and the high dose JYXR group (P <0. 05). Compared with the positive control group, expression levels of Fas, and Bax were all down-regulated, but expression levels of Bcl-2, Cyclin D2, and Cyclin D3 were all up-regulated in the high dose JYXR group and the low dose JYXR group (all P <0. 05). The expression level of Cyclin D1 was down-regulated in the high dose JYXR group, but it was up-regulated in the low dose JYXR group ( both P <0. 05). (3) Results of Western blot showed, compared with the negative control group, expression levels of Procaspase-3, Procaspase-8, and Procaspase-9 were down-regulated, but expression levels of cleaved-PARP, Beclin-1, and LC3B II were up-regulated in the high dose JYXR group and the low dose JYXR group (all P <0.05). Compared with the negative control group, expression levels of Procaspase-3, Procaspase-8, Procaspase-9, and LC3B II were down-regulated, but expression levels of cleaved-PARP, Beclin-1, and LC3B I were up-regulated in the positive control group (all P <0. 05). JYXR showed significant inhibition on subcutaneous transplanted tumor gastric cancer cell line MGC-803 in BALB/c nude mice. Its mechanism might be associated with activating apoptosis and autophagy correlated factors.

Vaccination coverage among children in kindergarten - United States, 2012-13 school year.

PubMed

2013-08-02

State and local school vaccination requirements are implemented to maintain high vaccination coverage and minimize the risk from vaccine preventable diseases. To assess school vaccination coverage and exemptions, CDC annually analyzes school vaccination coverage data from federally funded immunization programs. These awardees include 50 states and the District of Columbia (DC), five cities, and eight U.S.-affiliated jurisdictions. This report summarizes vaccination coverage from 48 states and DC and exemption rates from 49 states and DC for children entering kindergarten for the 2012-13 school year. Forty-eight states and DC reported vaccination coverage, with medians of 94.5% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.1% for local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccination; and 93.8% for 2 doses of varicella vaccine among awardees with a 2-dose requirement. Forty-nine states and DC reported exemption rates, with the median total of 1.8%. Although school entry coverage for most awardees was at or near national Healthy People 2020 targets of maintaining 95% vaccination coverage levels for 2 doses of MMR vaccine, 4 doses of DTaP† vaccine, and 2 doses of varicella vaccine, low vaccination and high exemption levels can cluster within communities, increasing the risk for disease. Reports to CDC are aggregated at the state level; however, local reporting of school vaccination coverage might be accessible by awardees. These local-level data can be used to create evidence-based health communication strategies to help parents understand the risks for vaccine-preventable diseases and the benefits of vaccinations to the health of their children and other kindergarteners.

Vaccination coverage among children in kindergarten - United States, 2013-14 school year.

PubMed

Seither, Ranee; Masalovich, Svetlana; Knighton, Cynthia L; Mellerson, Jenelle; Singleton, James A; Greby, Stacie M

2014-10-17

State and local vaccination requirements for school entry are implemented to maintain high vaccination coverage and protect schoolchildren from vaccine-preventable diseases. Each year, to assess state and national vaccination coverage and exemption levels among kindergartners, CDC analyzes school vaccination data collected by federally funded state, local, and territorial immunization programs. This report describes vaccination coverage in 49 states and the District of Columbia (DC) and vaccination exemption rates in 46 states and DC for children enrolled in kindergarten during the 2013-14 school year. Median vaccination coverage was 94.7% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.0% for varying local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccine; and 93.3% for 2 doses of varicella vaccine among those states with a 2-dose requirement. The median total exemption rate was 1.8%. High exemption levels and suboptimal vaccination coverage leave children vulnerable to vaccine-preventable diseases. Although vaccination coverage among kindergartners for the majority of reporting states was at or near the 95% national Healthy People 2020 targets for 4 doses of DTaP, 2 doses of MMR, and 2 doses of varicella vaccine, low vaccination coverage and high exemption levels can cluster within communities. Immunization programs might have access to school vaccination coverage and exemption rates at a local level for counties, school districts, or schools that can identify areas where children are more vulnerable to vaccine-preventable diseases. Health promotion efforts in these local areas can be used to help parents understand the risks for vaccine-preventable diseases and the protection that vaccinations provide to their children.

3,3′,4,4′,5-Pentachlorobiphenyl (PCB 126) Decreases Hepatic and Systemic Ratios of Epoxide to Diol Metabolites of Unsaturated Fatty Acids in Male Rats

PubMed Central

Wu, Xianai; Yang, Jun; Morisseau, Christophe; Robertson, Larry W.; Hammock, Bruce; Lehmler, Hans-Joachim

2016-01-01

Disruption of the homeostasis of oxygenated regulatory lipid mediators (oxylipins), potential markers of exposure to aryl hydrocarbon receptor (AhR) agonists, such as 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), is associated with a range of diseases, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Here we test the hypothesis that PCB 126 exposure alters the levels of oxylipins in rats. Male Sprague-Dawley rats (5-weeks old) were treated over a 3-month period every 2 weeks with intraperitoneal injections of PCB 126 in corn oil (cumulative doses of 0, 19.8, 97.8, and 390 µg/kg b.w.; 6 injections total). PCB 126 treatment caused a reduction in growth rates at the highest dose investigated, a dose-dependent decrease in thymus weights, and a dose-dependent increase in liver weights. Liver PCB 126 levels increased in a dose-dependent manner, while levels in plasma were below or close to the detection limit. The ratios of several epoxides to diol metabolites formed via the cytochrome P450 (P450) monooxygenase/soluble epoxide hydrolase (sEH) pathway from polyunsaturated fatty acids displayed a dose-dependent decrease in the liver and plasma, whereas levels of oxylipins formed by other metabolic pathways were generally not altered by PCB 126 treatment. The effects of PCB 126 on epoxide-to-diol ratios were associated with an increased CYP1A activity in liver microsomes and an increased sEH activity in liver cytosol and peroxisomes. These results suggest that oxylipins are potential biomarkers of exposure to PCB 126 and that the P450/sEH pathway is a therapeutic target for PCB 126-mediated hepatotoxicity that warrants further attention. PMID:27208083

Intermittent minodronic acid treatment with sufficient bone resorption inhibition prevents reduction in bone mass and strength in ovariectomized rats with established osteopenia comparable with daily treatment.

PubMed

Kimoto, Aishi; Tanaka, Makoto; Nozaki, Kazutoshi; Mori, Masamichi; Fukushima, Shinji; Mori, Hiroshi; Shiroya, Tsutomu; Nakamura, Toshitaka

2013-07-01

This study examined and compared the effects of four-week intermittent and daily administrations of minodronic acid, a highly potent nitrogen-containing bisphosphonate, on bone mineral density (BMD), bone strength, bone turnover, and histomorphometry on established osteopenia in ovariectomized (OVX) rats. Fourteen-week-old female F344 rats were OVX or sham-operated. At 12 weeks post surgery, minodronic acid was orally administered once every 4 weeks at 0.2, 1, and 5 mg/kg and once daily at 0.006, 0.03, and 0.15 mg/kg for 12 months. The total dosing amount was comparable between the two dosing regimens. The levels of urinary deoxypyridinoline and serum osteocalcin were measured to assess bone turnover. BMD as assessed via dual-energy X-ray absorptiometry, bone structure and dynamical changes in vertebral trabecula and biomechanical properties were measured ex vivo at 12 months to assess bone content and material properties. Minodronic acid dose-dependently ameliorated the decrease in BMD of lumbar vertebrae and the femur in both treatment regimens similarly. Minodronic acid suppressed elevated urinary levels of deoxypyridinoline, a bone resorption marker, and reduced the serum levels of osteocalcin, a bone formation marker. In the mechanical test at 12 months of treatment, minodronic acid dose-dependently ameliorated the reduction in bone strength in femur and vertebral body. There is no significant difference in parameters between the two regimens except maximal load of lower doses in lumbar vertebral body and absorption energy of middle doses in femur. With these parameters with significant differences, values of the intermittent regimen were significantly lower than that of daily repeated regimen. Bone histomorphometric analysis of the lumbar vertebral body showed that minodronic acid significantly ameliorated the decrease in bone mass, trabecular thickness and number, and the increase in trabecular separation, bone resorption indices (Oc.S/BS and N.Oc/BS), and bone formation indices (BFR/BS, MAR and OV/BV) in both regimens. Minodronic acid suppressed OVX-induced increases in bone turnover at the tissue level and ameliorated all structural indices, thereby improving the deterioration of bone quality under osteoporotic disease conditions regardless of the regimen. In conclusion, a four-week intermittent treatment of minodronic acid suppressed increased bone resorption as daily treatment when considering the total administered dose in OVX rats with established osteopenia. The improvement of microarchitectural destruction in low dose of intermittent treatment was weaker than that observed in a daily repeated regimen; however the effects of high and middle doses of intermittent treatment were equivalent to that observed in daily repeated regimen accompanied by sufficient bone resorption inhibition in rats. These findings suggest that minodronic acid at an appropriate dose in an intermittent regimen may be as clinically useful in osteoporosis therapy as in daily treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Performance traits and metabolic responses in goats (Capra hircus) supplemented with inorganic trivalent chromium.

PubMed

Haldar, Sudipto; Mondal, Souvik; Samanta, Saikat; Ghosh, Tapan Kumar

2009-11-01

The effects of supplemental chromium (Cr) as chromic chloride hexahydrate in incremental dose levels (0, 0.5, 1.0, and 1.5 mg/day for 240 days) on metabolism of nutrients and trace elements were determined in dwarf Bengal goats (Capra hircus, castrated males, average age 3 months, n = 24, initial mean body weight 6.4 +/- 0.22 kg). Live weight increased linearly (p < 0.05) with the level of supplemental Cr. Organic matter and crude protein digestibility, intake of total digestible nutrients, and retention of N (g/g N intake) increased (p < 0.05) in a dose-dependent linear manner. Serum cholesterol and tryacylglycerol concentrations changed inversely with the dose of supplemental Cr (p < 0.01). Supplemental Cr positively influenced retention of copper and iron (p < 0.05) causing linear increase (p < 0.01) in their serum concentrations. It was concluded that Cr supplementation may improve utilization of nutrients including the trace elements and may also elicit a hypolidemic effect in goats. However, further study with regards to optimization of dose is warranted.

Effects of isoflavone supplements vs. soy foods on blood concentrations of genistein and daidzein in adults

PubMed Central

Gardner, Christopher D.; Chatterjee, Lorraine M.; Franke, Adrian A.

2012-01-01

The objective of this investigation was to examine the pharmacokinetics of isoflavone concentrations over a 24-hour period among healthy adults consuming either soy foods or soy isoflavone tablets at different doses. This randomized, cross-over trial was conducted with twelve generally healthy adults. The three phases of the intervention included: isoflavone tablets at 1) 144 mg/day or 2) 288 mg/day, and 3) soy foods designed to provide a calculated 96 mg isoflavones/day (doses in aglycone equivalents). Doses were spread out over three meals/day. After 6 days on each study phase, plasma isoflavone concentrations were determined on the seventh day at 0, 4, 8, 10, 12 and 24 hours. Average levels of total isoflavone concentrations at 8, 10 and 12 hours were >4 μmol/L for the soy food phase and for the higher dose tablet phase. Genistein concentrations were higher overall in the soy food vs. both the lower and the higher dose supplement phases of the study (p≤0.05). When comparing plasma concentrations for the two doses of tablets, saturation appeared more evident for genistein than daidzein at the higher dose level. In conclusion, we observed important differences in the pharmacokinetics of genistein and daidzein contrasting the sources and doses of isoflavones when administered three times daily, including a possible advantage for increasing serum concentrations of isoflavones from consuming soy foods relative to isoflavone supplements. PMID:18602820

Effects of isoflavone supplements vs. soy foods on blood concentrations of genistein and daidzein in adults.

PubMed

Gardner, Christopher D; Chatterjee, Lorraine M; Franke, Adrian A

2009-03-01

The objective of this investigation was to examine the pharmacokinetics of isoflavone concentrations over a 24-h period among healthy adults consuming either soy foods or soy isoflavone tablets at different doses. This randomized, cross-over trial was conducted with 12 generally healthy adults. The three phases of the intervention included isoflavone tablets at (1) 144 mg/day or (2) 288 mg/day and (3) soy foods designed to provide a calculated 96 mg isoflavones/day (doses in aglycone equivalents). Doses were spread out over three meals per day. After 6 days on each study phase, plasma isoflavone concentrations were determined on the seventh day at 0, 4, 8, 10, 12 and 24 h. Average levels of total isoflavone concentrations at 8, 10 and 12 h were >4 micromol/L for the soy food phase and for the higher dose tablet phase. Genistein concentrations were higher overall in the soy food vs. both the lower and the higher dose supplement phases of the study (P<.05). When comparing plasma concentrations for the two doses of tablets, saturation appeared more evident for genistein than for daidzein at the higher dose level. In conclusion, we observed important differences in the pharmacokinetics of genistein and daidzein contrasting the sources and doses of isoflavones when administered three times daily, including a possible advantage for increasing serum concentrations of isoflavones from consuming soy foods relative to isoflavone supplements.

Cosmic radiation dose in aircraft--a neutron track etch detector.

PubMed

Vuković, B; Radolić, V; Miklavcić, I; Poje, M; Varga, M; Planinić, J

2007-01-01

Cosmic radiation bombards us at high altitude by ionizing particles. The radiation environment is a complex mixture of charged particles of solar and galactic origin, as well as of secondary particles produced in interaction of the galactic cosmic particles with the nuclei of atmosphere of the Earth. The radiation field at aircraft altitude consists of different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard ATR 42 and A 320 aircrafts (flight level of 8 and 11 km, respectively) was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter. The estimated occupational effective dose for the aircraft crew (A 320) working 500 h per year was 1.64 mSv. Other experiments, or dose rate measurements with the neutron dosimeter, consisting of LR-115 track detector and boron foil BN-1 or 10B converter, were performed on five intercontinental flights. Comparison of the dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level showed that the neutron component carried about 50% of the total dose. The dose rate measurements on the flights from the Middle Europe to the South and Middle America, then to Korea and Japan, showed that the flights over or near the equator region carried less dose rate; this was in accordance with the known geomagnetic latitude effect.

Effect of γ irradiation on fungal load and aflatoxins reduction in red chillies

NASA Astrophysics Data System (ADS)

Iqbal, Shahzad Zafar; Bhatti, Ijaz Ahmad; Asi, Muhammad Rafique; Zuber, Mohammad; Shahid, Muhammad; Parveen, Ishrat

2013-01-01

Chillies are a very important cash crop of Pakistan. The effects of gamma irradiation on microbial load, aflatoxin B1 (AFB1) and total aflatoxins have been studied in chillies samples, collected from different districts of Punjab, Pakistan. Aflatoxins were analyzed using HPLC equipped with a fluorescence detector. The results revealed that among the Aspergillus species isolated, those belonging to section parasiticus were predominant. Gamma radiations of doses 2, 4 and 6 kGy were employed on fungi and chilli samples. The results have demonstrated that the dose of 6 kGy reduced the fungal load by 5 logs. Furthermore, 6 kGy reduced the level of AFB1 and total AFs in ground and whole chillies by 1-2 logs (α < 0.05).

Postnatal iron-induced motor behaviour alterations following chronic neuroleptic administration in mice.

PubMed

Fredriksson, A; Eriksson, P; Archer, T

2006-02-01

C57/BL6 mice were administered either 7.5 mg Fe(2+)/kg or vehicle (saline) postnatally on days 10-12 after birth. From 61 days of age onwards for 21 days, groups of mice were administered either clozapine (1 or 5 mg/kg, s.c.) or haloperidol (1 mg/kg, s.c.) or vehicle (Tween-80). Twenty-four hours after the final injection of either neuroleptic compound or vehicle, spontaneous motor activity was measured over a 60-min interval. Following this, each animal was removed, injected apomorphine (1 mg/kg, s.c.) and replaced in the same test chamber. It was found that postnatal administration of Fe(2+) at the 7.5 mg/kg dose level reduced activity during the initial 20-min periods (0-20 and 20-40 min) and then induced hyperactivity during the final 20-min period over all three parameters of activity. Subchronic treatment with the higher, 5 mg/kg, dose of clozapine abolished or attenuated the hypoactivity in by postnatal Fe(2+) during the 1(st) two 20-min periods over all three parameters of activity. Subchronic treatment with the higher, 5 mg/kg, dose of clozapine abolished or attenuated the hyperactivity in by postnatal Fe(2+) during the 3(rd) and final 20-min period. Subchronic administration of haloperidol, without postnatal iron, increased the level of both locomotion (1(st) 20 min) and rearing (2(nd) 20 min) activity. Postnatal administration of Fe(2+) at the 7.5 mg/kg dose increased the levels of both locomotion and rearing, but not total activity, following administration of apomorphine (1 mg/kg). Subchronic administration of clozapine, at both the 1 and 5 mg/kg doses, reduced the increased locomotor activity caused by postnatal Fe(2+), whereas clozapine, 5 mg/kg, elevated further the postnatal Fe(2+)-induced increased in rearing. Subchronic administration of clozapine, at both the 1 and 5 mg/kg doses, and haloperidol, 1 mg/kg, increased the level of locomotor following administration of apomorphine (1 mg/kg) in mice treated postnatally with vehicle, whereas only clozapine increased the level of rearing. Correlational analyses indicated that both apomorphine-induced locomotion and rearing were highly correlated with the total iron content in the basal ganglia, thereby offering direct evidence of the linear relationship between iron content in the basal ganglia and the behavioural expression of DA D(2)-receptor supersensitivity in mice.

Studies of young female responses to acute ozone exposure. Final report

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

Adams, W.C.

The primary purposes of this research were to determine if: (1) young adult females respond with greater acute effects of ozone (O3) than their male counterparts at a dose relative to lung size as well as at the same total dose; (2) O3 response in females is influenced by the disparate levels of progesterone (a steroid hormone) that they experience during the various phases of their menstrual cycles; and (3) O3 exposure has an effect on the integrity of normal menstrual cycles of healthy young adult females.

Dose-response association of physical activity with acute myocardial infarction: do amount and intensity matter?

PubMed

Elosua, Roberto; Redondo, Ana; Segura, Antonio; Fiol, Miquel; Aldasoro, Elena; Vega, Gema; Forteza, Jordi; Martí, Helena; Arteagoitia, José María; Marrugat, Jaume

2013-11-01

The aims of this study were to analyze the dose-response association between leisure time physical activity (PA) practice and myocardial infarction (MI), considering not only the total amount but also the amount of PA at different levels of intensity, and to determine whether these associations were modified by age. In a population-based age- and sex-matched case-control study, all first acute MI patients aged 25 to 74 years were prospectively registered in four Spanish hospitals between 2002 and 2004. Controls were randomly selected from population-based samples recruited during the same period of time. The Minnesota PA questionnaire was administered to assess total energy expenditure in PA and in light-, moderate-, and high-intensity PA. Finally, 1339 cases and 1339 controls were included. The association between PA and MI likelihood was non-linear, with significantly lower MI odds at low practice levels (≥ 500 MET·min/week), lowest odds around 1500 MET·min/week, and a plateau thereafter. Light- (in subjects older than 64 years), moderate-, and high-intensity PA produced similar benefits. Most of the population could reduce their likelihood of MI by engaging in PA at a moderate level of intensity or, in individuals older than 64 years, at a light level of intensity. © 2013.

Candida albicans gastrointestinal colonization and invasion in the mouse: effect of antibacterial dosing, antifungal therapy and immunosuppression.

PubMed

Kinsman, O S; Pitblado, K

1989-12-01

Infant mice infected with Candida albicans by the oral-intragastric route became colonized in the gut and were persistently colonized into adulthood. Faecal levels of Candida were correlated with total gastrointestinal Candida and provided a useful means of detecting yeast overgrowth or elimination. Antibacterial agents promoting Candida overgrowth when given by the oral or parenteral route included ceftriaxone, augmentin and cefoperazone. Ceftizoxime had less effect. Ceftazidime and latamoxef produced raised levels only by the oral route. Gentamicin, vancomycin and metronidazole did not affect the Candida levels. Dosing with some antibacterials promoted an increase in gastrointestinal Candida and invasion to a greater extent than immunosuppression. Antifungal therapy to reduce gastrointestinal colonization was investigated using amphotericin B, nystatin, ketoconazole, intraconazole and fluconazole. Fluconazole was most effective at reducing faecal Candida.

Optical fibres in the radiation environment of CERN

NASA Astrophysics Data System (ADS)

Guillermain, E.

2017-11-01

CERN, the European Organization for Nuclear Research (in Geneva, Switzerland), is home to a complex scientific instrument: the 27-kilometre Large Hadron Collider (LHC) collides beams of high-energy particles at close to the speed of light. Optical fibres are widely used at CERN, both in surface areas (e.g. for inter-building IT networks) and in the accelerator complex underground (e.g. for cryogenics, vacuum, safety systems). Optical fibres in the accelerator are exposed to mixed radiation fields (mainly composed of protons, pions, neutrons and other hadrons, gamma rays and electrons), with dose rates depending on the particular installation zone, and with radiation levels often significantly higher than those encountered in space. In the LHC and its injector chain radiation levels range from relatively low annual doses of a few Gy up to hundreds of kGy. Optical fibres suffer from Radiation Induced Attenuation (RIA, expressed in dB per unit length) that affect light transmission and which depends on the irradiation conditions (e.g. dose rate, total dose, temperature). In the CERN accelerator complex, the failure of an optical link can affect the proper functionality of control or monitoring systems and induce the interruption of the accelerator operation. The qualification of optical fibres for installation in critical radiation areas is therefore crucial. Thus, all optical fibre types installed in radiation areas at CERN are subject to laboratory irradiation tests, in order to evaluate their RIA at different total dose and dose rates. This allows the selection of the appropriate optical fibre type (conventional or radiation resistant) compliant with the requirements of each installation. Irradiation tests are performed in collaboration with Fraunhofer INT (irradiation facilities and expert team in Euskirchen, Germany). Conventional off-the-shelf optical fibres can be installed for optical links exposed to low radiation levels (i.e. annual dose typically below few kGy). Nevertheless, the conventional optical fibres must be carefully qualified as a spread in RIA of factor 10 is observed among optical fibres of different types and dopants. In higher radiation areas, special radiation resistant optical fibres are installed. For total dose above 1 kGy, the RIA of these special optical fibres is at least 10 times lower than the conventional optical fibres RIA at same irradiation conditions. 2400 km of these special radiation resistant optical fibres were recently procured at CERN. As part of this procurement process, a quality assurance plan including the irradiation testing of all 65 produced batches was set up. This presentation will review the selection process of the appropriate optical fibre types to be installed in the radiation environment of CERN. The methodology for choosing the irradiation parameters for the laboratory tests will be discussed together with an overview of the RIA of different optical fibre types under several irradiation conditions.

Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels

PubMed Central

Lovallo, William R.; Whitsett, Thomas L.; al'Absi, Mustafa; Sung, Bong Hee; Vincent, Andrea S.; Wilson, Michael F.

2008-01-01

Objective Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake. Methods Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or 250 mg at 9:00 AM, 1:00 PM, and 6:00 PM, and cortisol was sampled from saliva collected at 8 times from 7:30 AM to 7:00 PM. Results After 5 days of caffeine abstinence, caffeine challenge doses caused a robust increase in cortisol across the test day (p < .0001). In contrast, 5 days of caffeine intake at 300 mg/day and 600 mg/day abolished the cortisol response to the initial 9:00 AM caffeine dose, although cortisol levels were again elevated between 1:00 PM and 7:00 PM (p = .02 to .002) after the second caffeine dose taken at 1:00 PM. Cortisol levels declined to control levels during the evening sampling period. Conclusion Cortisol responses to caffeine are reduced, but not eliminated, in healthy young men and women who consume caffeine on a daily basis. PMID:16204431

SU-F-T-648: Sharpening Dose Fall-Off Via Beam Number Enhancements For Stereotactic Brain Radiosurgery

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

Chiu, J; Braunstein, S; McDermott, M

Purpose: Sharp dose fall-off is the hallmark of brain radiosurgery to deliver a high dose of radiation to the target while minimizing dose to normal brain tissue. In this study, we developed a technique for the purpose of enhancing the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter via patient head tilt and simultaneous beam intensity modulations. Methods: Computer scripting for the proposed beam number enhancement (BNE) technique was developed. The technique was tested and then implemented on a clinical treatment planning system for a dedicated brain radiosurgical system (GK Perfexion, Elekta Oncology). Tomore » study technical feasibility and dosimetric advantages of the technique, we compared treatment planning quality and delivery efficiency for 20 radiosurgical cases previously treated at our institution. These cases included relatively complex treatments such as acoustic schwannoma, meningioma, brain metastasis and mesial temporal lobe epilepsy. Results: The BNE treatment plans were found to produce nearly identical target volume coverage (absolute value < 0.5%, P > 0.2) and dose conformity (BNE CI= 1.41±0.15 versus 1.41±0.20, P>0.9) as the original treatment plans. The total beam-on time for theBNE treatment plans were comparable (within 1.0 min or 1.8%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI = 2.9±0.3 versus original GI =3.0±0.3 p<0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 2.0% to 5.0% (p<0.02). Furthermore, with 4 to 5-fold increase in the total number of beams, the GI decreased by as much as 20% or 0.5 in absolute values. Conclusion: BNE via head tilt and simultaneous beam intensity modulation is an effective and efficient technique that physically sharpens the peripheral dose gradient for brain radiosurgery.« less

Total body irradiation, toward optimal individual delivery: dose evaluation with metal oxide field effect transistors, thermoluminescence detectors, and a treatment planning system.

PubMed

Bloemen-van Gurp, Esther J; Mijnheer, Ben J; Verschueren, Tom A M; Lambin, Philippe

2007-11-15

To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

Comparison between in vivo dosimetry and barium contrast technique for prediction of rectal complications in high-dose-rate intracavitary radiotherapy in cervix cancer patients.

PubMed

Huh, Seung Jae; Lim, Do Hoon; Ahn, Yong Chan; Lee, Jeong Eun; Kang, Min Kyu; Shin, Seong Soo; Shin, Kyung Hwan; Kim, Bokyung; Park, Won; Han, Youngyih

2003-03-01

To investigate the correlation between late rectal complications and rectal dose in cervix cancer patients treated with high-dose-rate intracavitary radiotherapy (HDR ICR) and to analyze factors reducing rectal complications. A total of 136 patients with cervix cancer who were treated with external beam radiotherapy (EBRT) and HDR ICR from 1995 to 1999 were retrospectively analyzed. Radiotherapy (RT) consisted of EBRT plus HDR ICR. The median EBRT dose was 50.4 Gy, and midline block was done after 30-50 Gy of EBRT. A total of six fractions of HDR ICR with 4 Gy fraction size each were applied twice per week to the A point. The rectal dose was calculated at the rectal reference point using the barium contrast criteria. In vivo measurement of the rectal dose was performed with thermoluminescent dosimeter (TLD) during HDR ICR. The median follow-up period was 26 months (range 6-60 months). A total of 16 patients (12%) experienced rectal bleeding, which occurred 4-33 months (median 11 months) after the completion of RT. The calculated rectal doses did not differ in patients with rectal bleeding and those without, but the measured rectal doses were higher in affected patients. The differences of the measured ICR fractional rectal dose, ICR total rectal dose, and total rectal biologically equivalent dose (BED) were statistically significant. When the measured ICR total rectal dose exceeded 16 Gy, the ratio of the measured rectal dose to A point dose was > 70%; when the measured rectal BED exceeded 110 Gy(3), a high possibility of late rectal complications could be found. In vivo dosimetry using TLD during HDR ICR was a good predictor of late rectal complications. Hence, if data from in vivo dosimetry shows any possibility of rectal bleeding, efforts should be made to reduce the rectal dose.

Hepatoprotective and Antioxidant Activity of Dunaliella salina in Paracetamol-induced Acute Toxicity in Rats

PubMed Central

Madkour, Fedekar F.; Abdel-Daim, M. M.

2013-01-01

Paracetamol has a reasonable safety profile when taken in therapeutic doses. However, it could induce hepatotoxicity and even more severe fatal acute hepatic damage when taken in an overdose. The green alga, Dunaliella salina was investigated for hepatoprotective and antioxidant activity against paracetamol-induced liver damage in rats. Male albino Wistar rats overdosed with paracetamol showed liver damage and oxidative stress as indicated by significantly (P<0.05) increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide. At the same time, there were decreased activities of serum superoxide dismutase and total antioxidant capacity compared with the control group. Treatment with D. salina methanol extract at doses of 500 and 1000 mg/kg body weight or silymarin could significantly (P<0.05) decrease the liver damage marker enzymes, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide levels and increase the activities of superoxide dismutase and total antioxidant capacity in serum when compared with paracetamol intoxicated group. Liver histopathology also showed that D. salina reduced the centrilobular necrosis, congestion and inflammatory cell infiltration evoked by paracetamol overdose. These results suggest that D. salina exhibits a potent hepatoprotective effect on paracetamol-induced liver damage in rats, which may be due to both the increase of antioxidant enzymes activity and inhibition of lipid peroxidation. PMID:24591738

Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis.

PubMed

Wu, Jashin J; Strober, Bruce E; Hansen, Peter R; Ahlehoff, Ole; Egeberg, Alexander; Qureshi, Abrar A; Robertson, Debbie; Valdez, Hernan; Tan, Huaming; Wolk, Robert

2016-11-01

Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in patients with plaque psoriasis. Changes in select CV risk factors and the incidence rate (IR) of MACEs were evaluated in patients who were treated with tofacitinib. Tofacitinib treatment was associated with small, dose-dependent increases in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was unchanged. There were no changes in blood pressure and glycated hemoglobin levels; C-reactive protein levels decreased. The IRs of a MACE were low and similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib, the total patient-years of exposure was 5204, with a median follow-up of 527 days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients with events per 100 patient-years. There was relatively short follow-up time for patients who had MACEs. While treatment with tofacitinib is associated with a small increase in cholesterol levels, the total/HDL cholesterol ratio does not change, there are no unfavorable changes in several CV risk factors, and the incidence of MACEs is low. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Effect of lipoprotein-associated phospholipase A2 inhibitor on insulin resistance in streptozotocin-induced diabetic pregnant rats.

PubMed

Wang, Guo-Hua; Jin, Jun; Sun, Li-Zhou

2018-06-21

This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.

High-dose anti-histamine use and risk factors in children with urticaria

PubMed Central

Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

2016-01-01

Aim The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. Material and Methods The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. Results The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p<0.0001). There was no difference between the two groups in terms of blood eosinophil and basophil counts, and serum total IgE levels (p>0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=−0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03–1.15]) and basopenia (OR: 6.77; CI 95%: [2.01–22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. Conclusion The requirement of high-dose H1-antihistamines was higher with children’s increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines. PMID:28123332

Improving microbiological safety and maintaining sensory and nutritional quality of pre-cut tomato and carrot by gamma irradiation

NASA Astrophysics Data System (ADS)

Mohácsi-Farkas, Cs.; Nyirő-Fekete, B.; Daood, H.; Dalmadi, I.; Kiskó, G.

2014-06-01

Pre-cut tomato and carrot were irradiated with doses of 1.0, 1.5 and 2 kGy. Unirradiated control and irradiated samples were compared organoleptically by a sensory panel. Microbiological analyses were performed directly after irradiation and during post-irradiation storage for 8 days at 5 °C. Ascorbic acid contents, composition of carotenoids and tocopherols were determined. Statistically significant differences of sensory scores between unirradiated and irradiated samples were observed only in the texture of sliced carrots. Total aerobic viable cell counts have been reduced by about two log cycles with 1.5 kGy dose. Total coliforms and moulds were below the detection limit of 15 CFU/g in the irradiated samples during the refrigerated storage. Yeasts were relatively resistant part of the microbiota of pre-cut tomatoes, but 2 kGy dose reduced them below the detection limit. In pre-cut tomatoes, alpha-tocopherol and some carotenoids seemed to be the most radio-sensitive losing approximately one-third of their original concentrations at the dose of 2 kGy. At this dose tocopherols and the level of ascorbic acid decreased also one-third of the initial level in sliced carrots. Additional experiments were conducted to study the effect of irradiation and storage on the population of Listeria monocytogenes and Listeria innocua artificially inoculated on cut tomato and carrot. Cell numbers of both test organisms decreased by at least two log-cycles as an effect of 1 kGy dose. Our studies confirmed earlier findings on a temporary antilisterial effect of freshly cut carrot tissue. No re-growth of Listeria was observed during the studied storage period. The results of these studies suggest that irradiation with 1 kGy gamma rays could improve sufficiently the microbiological safety of the investigated pre-cut produce to satisfy the requirement of low microbial raw diets with acceptable nutritional quality and without diminishing significantly the organoleptic parameters of the commodities.

Radiation exposure in the young level 1 trauma patient: a retrospective review.

PubMed

Gottschalk, Michael B; Bellaire, Laura L; Moore, Thomas

2015-01-01

Computed tomography (CT) has become an increasingly popular and powerful tool for clinicians managing trauma patients with life-threatening injuries, but the ramifications of increasing radiation burden on individual patients are not insignificant. This study examines a continuous series of 337 patients less than 40 years old admitted to a level 1 trauma center during a 4-month period. Primary outcome measures included number of scans; effective dose of radiation from radiographs and CT scans, respectively; and total effective dose from both sources over patients' hospital stays. Several variables, including hospital length of stay, initial Glasgow Coma Scale score, and Injury Severity Score, correlated with greater radiation exposure. Blunt trauma victims were more prone to higher doses than those with penetrating or combined penetrating and blunt trauma. Location and mechanism of injury were also found to correlate with radiation exposure. Trauma patients as a group are exposed to high levels of radiation from X-rays and CT scans, and CT scans contribute a very high proportion (91.3% ± 11.7%) of that radiation. Certain subgroups of patients are at a particularly high risk of exposure, and greater attention to cumulative radiation dose should be paid to patients with the above mentioned risk factors.

Behavioral effects of microwaves: relationship of total dose and dose rate

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

O'Connor, M.E.; Strattan, R.

1988-10-01

The goal of the research was to compare the relationship of whole-body averaged specific absorption rate (SAR) and specific absorption (SA) to determine whether dose rate or dose was the better predictor of biological effects. Sperm-positive Long-Evans female rats were exposed to 2450-MHz CW microwave radiation for 1-3 hours at approximately 10 W/kg. The maternal subjects were then observed for natural delivery of their litters. Sensitivity to thermally induced seizures and huddling were studied in the offspring. Analyses revealed that there were no statistically significant differences between exposed and control offspring on the behavioral indices. The behavior did not appearmore » to be affected by prenatal exposure to microwave radiation at this level. The huddle sizes became smaller as the pups aged both in exposed and control offspring.« less

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

PubMed

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

New Approach to Total Dose Specification for Spacecraft Electronics

NASA Technical Reports Server (NTRS)

Xapsos, Michael

2017-01-01

Variability of the space radiation environment is investigated with regard to total dose specification for spacecraft electronics. It is shown to have a significant impact. A new approach is developed for total dose requirements that replaces the radiation design margin concept with failure probability during a mission.

LTC1877 High Efficiency Regulator Total Ionizing Dose Test Report

NASA Technical Reports Server (NTRS)

Oldham, Timothy; Pellish, Jonathan; Boutte, Alvin

2012-01-01

This report presents total ionizing dose evaluation data for the Linear Technology Corporation LTC1877 high efficiency monolithic synchronous step-down regulator. Data sheet parameters were tracked as a function of ionizing dose up to a total of 20 krad(SiO2). Control devices were also used.

Ameliorative effect of hydro-methanolic extract from roots of Rauwolfia serpentina on some biochemical parameters of type 1 diabetic mice.

PubMed

Azmi, Muhammad Bilal; Qureshi, Shamim A; Ahmed, Syed Danish Haseen; Mudassir, Hina Akram; Imtiaz, Fauzia; Rais, Sumera; Khan, Auwais Ahmed; Ahsan, Muhammad

2018-03-01

Present work seeks to investigate the biochemical parameters in terms of hypoglycemic and hypolipidemic effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 (alloxan induced) diabetic mice. Animals were divided into seven groups, four control groups, and three were test groups (HyMREt at 50, 100, & 150mg/kg). Each treatment was repeated for 14 days regularly in all seven respective groups and afterwards the body weights, fasting blood glucose (FBG), insulin, and serum lipid levels were determined. Total body weights of diabetic mice treated with HyMREt extract were dose dependently (p<0.05) improved. FBG of test groups were significantly (p<0.0001) reduced in comparison with diabetic controls which displayed elevated fasting blood glucose level. The insulin levels of HyMREt treated groups were significantly (p<0.0001) higher than those of diabetic controls. Lower triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and very low density lipoprotein cholesterol (VLDL-c) whereas elevated level of high density lipoprotein cholesterol (HDL-c) were observed in test dose treated groups. In comparison with diabetic controls, the converse levels of serum lipid were observed. Significant improvement in cardio-protective indices and coronary risk index was also observed. Findings of present study support the hypoglycemic and hypolipidemic potential of HyMREt of R. serpentina.

An In Vivo Study of Low-Dose Intra-Articular Tranexamic Acid Application with Prolonged Clamping Drain Method in Total Knee Replacement: Clinical Efficacy and Safety

PubMed Central

Sa-ngasoongsong, Paphon; Chanplakorn, Pongsthorn; Wongsak, Siwadol; Uthadorn, Krisorn; Panpikoon, Tanapong; Jittorntam, Paisan; Aryurachai, Katcharin; Angchaisukisiri, Pantap; Kawinwonggowit, Viroj

2015-01-01

Background. Recently, combined intra-articular tranexamic acid (IA-TXA) injection with clamping drain method showed efficacy for blood loss and transfusion reduction in total knee replacement (TKR). However, until now, none of previous studies revealed the effect of this technique on pharmacokinetics, coagulation, and fibrinolysis. Materials and Methods. An experimental study was conducted, during 2011-2012, in 30 patients undergoing unilateral TKR. Patients received IA-TXA application and then were allocated into six groups regarding clamping drain duration (2-, 4-, 6-, 8-, 10-, and 12-hours). Blood and drainage fluid were collected to measure tranexamic acid (TXA) level and related coagulation and fibrinolytic markers. Postoperative complication was followed for one year. Results. There was no significant difference of serum TXA level at 2 hour and 24 hour among groups (p < 0.05). Serum TXA level at time of clamp release was significantly different among groups with the highest level at 2 hour (p < 0.0001). There was no significant difference of TXA level in drainage fluid, postoperative blood loss, blood transfusion, and postoperative complications (p < 0.05).  Conclusions. Low-dose IA-TXA application in TKR with prolonged clamping drain method is a safe and effective blood conservative technique with only minimal systemic absorption and without significant increase in systemic absorption over time. PMID:26583092

Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of antioxidant enzyme systems.

PubMed

Mandal, Tapas K; Das, Nildari S

2010-02-01

Intraperitoneal injection of cannabis extract at low doses (total doses ranging from 40 mg to 60 mg per mouse) induced adverse effect on testes and oxidative stress. At low doses, there was a significant increase in lipid peroxidation and decrease in testicular lipid content, but the effects were significantly less at higher doses and at the withdrawal of cannabis treatment (recovery dose). There was a marked decrease in antioxidant enzyme profiles (superoxide dismutase, catalase and glutathione peroxidase) and glutathione content at low doses, but these effects were higher at higher dose and at withdrawal of the treatment (recovery effect). Histology revealed significant shrinkage of tubular diameter and detrimental changes in seminiferous epithelium of testis with resulting lowered serum testosterone and pituitary gonadotropins (follicular stimulating [FSH] and luteinizing hormones [LH]) levels at low doses. But at higher doses and particularly at withdrawal of the treatment, regression of various germ cell layers of testes through the revival of testosterone hormone and pituitary gonadotropins (FSH and LH) were observed, indicating that recovery effects on testes became operative possibly through the corrective measure of endogenous testicular antioxidant enzymes profiles and pituitary gonadotropins hormones feedback mechanisms.

Total dose bias dependency and ELDRS effects in bipolar linear devices

NASA Technical Reports Server (NTRS)

Yui, C. C.; McClure, S. S.; Rex, B. G.; Lehman, J. M.; Minto, T. D.; Wiedeman, M.

2002-01-01

Total dose tests of several bipolar linear devices show sensitivity to both dose rate and bias during exposure. All devices exhibited Enhanced Low Dose Rate Sensitivity (ELDRS). An accelerated ELDRS test method for three different devices demonstrate results similar to tests at low dose rate. Behavior and critical parameters from these tests are compared and discussed.

Effects of Lentinula edodes consumption on biochemical, hematologic and oxidative stress parameters in rats receiving high-fat diet.

PubMed

Spim, Sara Rosicler Vieira; de Oliveira, Bruna Giovanna Corrêa Chrispim; Leite, Fernanda Gomes; Gerenutti, Marli; Grotto, Denise

2017-10-01

Functional foods can prevent/reduce the risks related to obesity. Lentinula edodes is a highly nutritious mushroom rich in protein, vitamins and minerals. Some studies have demonstrated the hypocholesterolemic effects from L. edodes in high doses, which does not represent the consumption in humans. We evaluated ingestion of a realistic dose of L. edodes associated with a high-fat diet (HFD) on hematologic, biochemical and oxidative stress parameters. Eighteen male Wistar rats were divided into three groups: control (normal diet); HFD; and HFD + L. edodes (100 mg/kg/day). After 30 days, blood was collected. Biochemical and hematologic parameters were analyzed, as well as oxidative stress biomarkers. The HFD increased levels of total cholesterol and triglycerides. Lentinula edodes reduced these parameters significantly to concentrations found in the control group. The HFD increased levels of alanine transaminase and aspartate transaminase (markers of liver damage). Lentinula edodes returned the levels of these enzymes to normal levels and normalized serum levels of urea (which were also increased owing to consumption of the HFD). Lentinula edodes reduced levels of urea and glucose. Lipid peroxidation was increased in rats receiving the HFD, and L. edodes reduced malondialdehyde levels, thereby preventing oxidation of fatty acids. Lentinula edodes was shown to have hypolipidemic, hypoglycemic, hepatoprotective and renoprotective features in doses that are suitable for humans.

Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure

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

Maier, Joscha, E-mail: joscha.maier@dkfz.de; Sawall, Stefan; Kachelrieß, Marc

2014-05-15

Purpose: Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levelsmore » from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Methods: Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Results: Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the HDTV algorithm shows the best performance. At 50 mGy, the deviation from the reference obtained at 500 mGy were less than 4%. Also the LDPC algorithm provides reasonable results with deviation less than 10% at 50 mGy while PCF and MKB reconstruction show larger deviations even at higher dose levels. Conclusions: LDPC and HDTV increase CNR and allow for quantitative evaluations even at dose levels as low as 50 mGy. The left ventricular volumes exemplarily illustrate that cardiac parameters can be accurately estimated at lowest dose levels if sophisticated algorithms are used. This allows to reduce dose by a factor of 10 compared to today's gold standard and opens new options for longitudinal studies of the heart.« less

Assessment of radiation doses from residential smoke detectors that contain americium-241

NASA Astrophysics Data System (ADS)

Odonnell, F. R.; Etnier, E. L.; Holton, G. A.; Travis, C. C.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv to 20 nSv for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 micro-Sv (0.0006 to 8 mrem) to total body and from 0.06 to 800 micro-Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft squared.

Fukushima radionuclides in the NW Pacific, and assessment of doses for Japanese and world population from ingestion of seafood

PubMed Central

Povinec, Pavel P.; Hirose, Katsumi

2015-01-01

Variations of Fukushima-derived radionuclides (90Sr, 134Cs and 137Cs) in seawater and biota offshore Fukushima and in the NW Pacific Ocean were investigated and radiation doses to the Japanese and world population from ingestion of seafood contaminated by Fukushima radionuclides were estimated and compared with those from other sources of anthropogenic and natural radionuclides. The total effective dose commitment from ingestion of radionuclides in fish, shellfish and seaweed caught in coastal waters off Fukushima was estimated to be 0.6 ± 0.4 mSv/y. The individual effective dose commitment from consumption of radioactive-contaminated fish caught in the open Pacific Ocean was estimated to be 0.07 ± 0.05 mSv/y. These doses are comparable or much lower than doses delivered from the consumption of natural 210Po in fish and in shellfish (0.7 mSv/y). The estimated individual doses have been below the levels when any health damage of the Japanese and world population could be expected. PMID:25761420

Diuretic downsides--but in low doses they still seem among the best authenticated antihypertensives.

PubMed

Opie, L H

2000-08-01

Diuretics in low doses have the greatest support among current available antihypertensives in that they have been shown to reduce total mortality, coronary mortality, stroke, and congestive heart failure in an important meta-analysis by Psaty. Recently, Messerli has linked longterm diuretic use to renal cell carcinoma in women. In some patients, diuretic use leads to increasing blood cholesterol and blood sugar levels. Impotence is a recognized side effect, with rates rising about twofold with low-dose chlorthalidone and fourfold with a higher dose. Certain population groups such as younger (<60 years) white males often do not respond to low-dose diuretic therapy with an adequate blood pressure fall. In females of a similar age group, Messerli calculates that prolonged diuretic therapy will prevent only one stroke and no coronary events nor any deaths for every renal cell carcinoma that is provoked. Despite these evident problems, the outcome data on hard endpoints in trials with initial low-dose diuretic therapy remain valid and convincing. Thus, it is argued, low- but not high-dose diuretics retain their primacy in the ranking of antihypertensive therapy.

Fukushima radionuclides in the NW Pacific, and assessment of doses for Japanese and world population from ingestion of seafood.

PubMed

Povinec, Pavel P; Hirose, Katsumi

2015-03-12

Variations of Fukushima-derived radionuclides ((90)Sr, (134)Cs and (137)Cs) in seawater and biota offshore Fukushima and in the NW Pacific Ocean were investigated and radiation doses to the Japanese and world population from ingestion of seafood contaminated by Fukushima radionuclides were estimated and compared with those from other sources of anthropogenic and natural radionuclides. The total effective dose commitment from ingestion of radionuclides in fish, shellfish and seaweed caught in coastal waters off Fukushima was estimated to be 0.6 ± 0.4 mSv/y. The individual effective dose commitment from consumption of radioactive-contaminated fish caught in the open Pacific Ocean was estimated to be 0.07 ± 0.05 mSv/y. These doses are comparable or much lower than doses delivered from the consumption of natural (210)Po in fish and in shellfish (0.7 mSv/y). The estimated individual doses have been below the levels when any health damage of the Japanese and world population could be expected.

Barriers to HIV Medication Adherence as a Function of Regimen Simplification.

PubMed

Chen, Yiyun; Chen, Kun; Kalichman, Seth C

2017-02-01

Barriers to HIV medication adherence may differ by levels of dosing schedules. The current study examined adherence barriers associated with medication regimen complexity and simplification. A total of 755 people living with HIV currently taking anti-retroviral therapy were recruited from community services in Atlanta, Georgia. Participants completed audio-computer-assisted self-interviews that assessed demographic and behavioral characteristics, provided their HIV viral load obtained from their health care provider, and completed unannounced phone-based pill counts to monitor medication adherence over 1 month. Participants taking a single-tablet regimen (STR) were more likely to be adherent than those taking multi-tablets in a single-dose regimen (single-dose MTR) and those taking multi-tablets in a multi-dose regimen (multi-dose MTR), with no difference between the latter two. Regarding barriers to adherence, individuals taking STR were least likely to report scheduling issues and confusion as reasons for missing doses, but they were equally likely to report multiple lifestyle and logistical barriers to adherence. Adherence interventions may need tailoring to address barriers that are specific to dosing regimens.

Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects.

PubMed

Samuels, Mary H; Kolobova, Irina; Niederhausen, Meike; Janowsky, Jeri S; Schuff, Kathryn G

2018-05-01

The brain is a critical target organ for thyroid hormone, but it is unclear whether variations in thyroid function within and near the reference range affect quality of life, mood, or cognition. A total of 138 subjects with levothyroxine (L-T4)-treated hypothyroidism and normal thyrotropin (TSH) levels underwent measures of quality of life (36-Item Short Form Health Survey, Underactive Thyroid-Dependent Quality of Life Questionnaire), mood (Profile of Mood States, Affective Lability Scale), and cognition (executive function, memory). They were then randomly assigned to receive an unchanged, higher, or lower L-T4 dose in double-blind fashion, targeting one of three TSH ranges (0.34 to 2.50, 2.51 to 5.60, or 5.61 to 12.0 mU/L). Doses were adjusted every 6 weeks based on TSH levels. Baseline measures were reassessed at 6 months. At the end of the study, by intention to treat, mean L-T4 doses were 1.50 ± 0.07, 1.32 ± 0.07, and 0.78 ± 0.08 μg/kg (P < 0.001), and mean TSH levels were 1.85 ± 0.25, 3.93 ± 0.38, and 9.49 ± 0.80 mU/L (P < 0.001), respectively, in the three arms. There were minor differences in a few outcomes between the three arms, which were no longer significant after correction for multiple comparisons. Subjects could not ascertain how their L-T4 doses had been adjusted (P = 0.55) but preferred L-T4 doses they perceived to be higher (P < 0.001). Altering L-T4 doses in hypothyroid subjects to vary TSH levels in and near the reference range does not affect quality of life, mood, or cognition. L-T4-treated subjects prefer perceived higher L-T4 doses despite a lack of objective benefit. Adjusting L-T4 doses in hypothyroid patients based on symptoms in these areas may not result in significant clinical improvement.

210Po, 210Pb, 40K and 137Cs in edible wild berries and mushrooms and ingestion doses to man from high consumption rates of these wild foods.

PubMed

Gwynn, Justin P; Nalbandyan, Anna; Rudolfsen, Geir

2013-02-01

This paper discusses activity concentrations of (210)Po, (210)Pb, (40)K and (137)Cs in edible wild berries and mushrooms collected from Øvre Dividalen national park, Northern Norway and derives committed effective ingestion doses to man based on high consumption rates of these wild foods. Edible wild berries and mushrooms accumulated similar levels of (210)Pb, but mushrooms accumulated higher levels of (210)Po and (40)K than berries. There appears to be a clear difference in the ability of Leccinum spp. of fungi to accumulate (210)Po and/or translocate (210)Po to mushrooms compared to Russula spp. of fungi. Activity concentrations of (137)Cs in edible wild berries and mushrooms from Øvre Dividalen national park reflected the lower levels of fallout of this radionuclide in Northern Norway compared to more central areas following the Chernobyl accident. For mushrooms, ingestion doses are dominated by (210)Po, while for berries, (40)K is typically the main contributor to dose. Based on high consumption rates, ingestion doses arising from the combination of (210)Po, (210)Pb and (40)K were up to 0.05 mSv/a for berries and 0.50 mSv/a for mushrooms. Consumption of such wild foods may result in a significant contribution to total annual doses when consumed in large quantities, particularly when selecting mushrooms species that accumulate high activity concentrations of (210)Po. Copyright © 2012 Elsevier Ltd. All rights reserved.

Erythemal UV at Davos (Switzerland), 1926-2003, estimated using total ozone, sunshine duration, and snow depth

NASA Astrophysics Data System (ADS)

Lindfors, Anders; Vuilleumier, Laurent

2005-01-01

A method previously developed for reconstructing daily erythemal UV doses at Sodankylä, northern Finland, was adjusted to the local conditions at Davos, Switzerland, and used for estimating the erythemal UV doses there over the period 1926-2003. The method uses total ozone, sunshine duration, and snow depth as input, and is based on the empirical relationship between relative sunshine duration and relative UV doses. In order to examine how the method behaves in different environments, the relationships found for Davos and Sodankylä were compared. This revealed that the surface albedo and the cloud climate have a comparable influence on the relationship found. Although the method is fairly simple, it accounts for the most important factors affecting the amount of UV radiation reaching the Earth's surface. A comparison between estimated UV doses and the corresponding observations with a broadband biometer at Davos demonstrated the good performance of the method. The correlation coefficient for daily values varies between 0.95 and 0.98 depending on time of year, and the corresponding root mean square error is typically of the order of 20%. The monthly mean values show considerably less scatter around the regression line with a root mean square error of 4%. The time series of estimated UV shows that the UV level at Davos has varied considerably throughout the period of this study, with high values in the middle of the 1940s, in the early 1960s, and in the 1990s. Variations in the estimated UV doses prior to 1980, e.g., a steady decrease from the early 1960s to the late 1970s, were found to be caused primarily by changes in sunshine duration. Since 1980, on the other hand, there has been a distinct increase in the UV level caused mainly by the diminution of total ozone. This increase is most clearly seen during winter and spring, while the decrease from the early 1960s to the late 1970s is most pronounced during summer.

Vitamin D supplementation in nursing home patients: randomized controlled trial of standard daily dose versus individualized loading dose regimen.

PubMed

Wijnen, Hugo; Salemink, Dayenne; Roovers, Lian; Taekema, Diana; de Boer, Hans

2015-05-01

Supplementation of cholecalciferol 800 IU daily appears to be insufficient to raise vitamin D levels to >75 nmol/l in nursing home (NH) patients. Our objective was to compare the efficacy of an individualized cholecalciferol loading dose (LD) regimen and a daily dose (DD) regimen of cholecalciferol 800 IU in reaching 25-OH vitamin D (25OHD) levels >75 nmol/l. A total of 30 NH patients with 25OHD levels <50 nmol/l were included. Patients were randomized using the minimization method in the LD or DD group. The cholecalciferol LD, calculated with an algorithm based on serum 25OHD level and body weight, was administered in divided doses of 50,000 IU twice a week, followed by a monthly maintenance dose of either 50,000 or 25,000 IU. The DD regimen consisted of cholecalciferol 800 IU daily for 26 weeks. Serum 25OHD, calcium, creatinine, phosphate, and parathyroid hormone were measured, and 2-minute walking test, handgrip strength, and timed get up and go test were assessed at baseline (T 0), after 5 weeks (T 5), 12 weeks (T 12), and 26 weeks (T 26). The primary endpoint was the percentage of patients with 25OHD levels >75 nmol/l at T 5. Secondary endpoints were the proportion of patients with 25OHD levels >75 nmol/l at T 26, safety of LD regimen, and improvement of performance tests with normalization of vitamin D levels. Median baseline 25OHD levels (interquartile range) were comparable between the 14 DD and 16 LD patients: 20.9 (15.9-29.6) and 21.7 (16.4-32.8) nmol/l, respectively. Levels of 25OHD >75 nmol/l at T 5 were reached in 79 % of the 14 LD patients, but in none of the 13 DD patients (p < 0.001). At T 26, 25OHD levels >75 nmol/l were reached in 83 % of the 12 LD patients and in 30 % of the ten DD patients (p < 0.05). Side effects or hypercalcemia were not observed. No improvement of performance tests was observed. In NH patients with severe 25OHD deficiency, an individualized calculated cholecalciferol LD is likely to be superior to a DD of cholecalciferol 800 IU in terms of the ability to rapidly normalize vitamin D levels.

Disposition of styrene-acrylonitrile (SAN) trimer in female rats: single dose intravenous and gavage studies.

PubMed

Gargas, Michael L; Collins, Brad; Fennell, Timothy R; Gaudette, Norman F; Sweeney, Lisa M

2008-04-21

Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano-1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile polymer. Disposition studies in female rats were conducted to evaluate the pharmacokinetic behavior of [3H]SAN Trimer following a single intravenous administration (26 mg/kg) to nonpregnant rats; a single gavage administration (nominal doses of 25 mg/kg, 75 mg/kg, or 200 mg/kg in corn oil) to nonpregnant rats; and a single gavage administration (nominal dose of 200 mg/kg in corn oil) to pregnant and lactating rats. SAN Trimer was rapidly eliminated from blood (T1/2 approximately 1h) following a single intravenous dose and following single oral doses (T1/2 approximately 3-4h). SAN Trimer was also rapidly excreted in the urine and feces following single oral doses, while total radioactivity was cleared more slowly. In pregnant rats, the concentrations of both radioactivity and SAN Trimer 2h after dosing were highest in the blood, followed by the placenta, with the lowest levels in the fetus. In lactating rats, the concentrations of both radioactivity and SAN Trimer were higher in milk than in maternal blood. Total radioactivity and SAN Trimer blood concentrations in nonpregnant, pregnant, and lactating rats were both higher in lactating rats compared to nonpregnant and pregnant rats.

Practice patterns of radiotherapy in cervical cancer among member groups of the Gynecologic Cancer Intergroup (GCIG).

PubMed

Gaffney, David K; Du Bois, Andreas; Narayan, Kailash; Reed, Nick; Toita, Takafumi; Pignata, Sandro; Blake, Peter; Portelance, Lorraine; Sadoyze, Azmat; Pötter, Richard; Colombo, Alessandro; Randall, Marcus; Mirza, Mansoor R; Trimble, Edward L

2007-06-01

The aim of this study was to describe radiotherapeutic practice of the treatment of cervical cancer in member groups of the Gynecologic Cancer Intergroup (GCIG). A survey was developed and distributed to the members of the GCIG focusing on details of radiotherapy practice. Different scenarios were queried including advanced cervical cancer, postoperative patients, and para-aortic-positive lymph node cases. Items focused on indications for radiation therapy, radiation fields, dose, use of chemotherapy, brachytherapy and others. The cooperative groups from North America were compared with the other groups to evaluate potential differences in radiotherapy doses. A total of 39 surveys were returned from 13 different cooperative groups. For the treatment of advanced cervical cancer, external beam pelvic doses and total doses to point A were 47 + 3.5 Gy (mean + SD) and 79.1 + 7.9 Gy, respectively. Point A doses were not different between the North American cooperative groups compared with the others (p = 0.103). All groups used concomitant chemotherapy, with 30 of 36 respondents using weekly cisplatin. Of 33 respondents, 31 intervened for a low hemoglobin level. For a para-aortic field, the upper border was most commonly (15 of 24) at the T12-L1 interspace. Maintenance chemotherapy (after radiotherapy) was not performed by 68% of respondents. For vaginal brachytherapy after hysterectomy, 23 groups performed HDR brachytherapy and four groups used LDR brachytherapy. In the use of brachytherapy, there was no uniformity in dose prescription. Radiotherapy practices among member groups of the GCIG are similar in terms of both doses and use of chemotherapy.

High brachytherapy doses can counteract hypoxia in cervical cancer—a modelling study

NASA Astrophysics Data System (ADS)

Lindblom, Emely; Dasu, Alexandru; Beskow, Catharina; Toma-Dasu, Iuliana

2017-01-01

Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased radioresistance caused by hypoxia if fast reoxygenation is assumed.

In vitro effect of low-level laser on odontoblast-like cells

NASA Astrophysics Data System (ADS)

Oliveira, C. F.; Basso, F. G.; Lins, E. C.; Kurachi, C.; Hebling, J.; Bagnato, V. S.; de Souza Costa, C. A.

2011-02-01

The aim of this study was to evaluate the metabolism of odontoblast-like MDPC-23 cells subjected to direct LLL irradiation. The cells were seeded (20,000 cells/well) in 24-well plates and incubated for 24 hours at 37°C. After this period, the culture medium (DMEM) was replaced by fresh DMEM supplemented with 2 or 5% (stress induction by nutritional deficit) or 10% fetal bovine serum (FBS). The cells were exposed to laser doses of 2, 4, 10, 15 and 25 J/cm2 from a near infrared InGaAsP diode laser prototype (LASERTable; 780±3 nm, 40 mW). One control group (sham irradiation) was established for each experimental condition (laser dose x FBS supplementation). Three and 72 hours after the last irradiation, cells were analyzed with respect to metabolism, morphology, total protein expression and alkaline phosphatase (ALP) activity. Higher metabolism and total protein expression were observed 72 hours after the last irradiation at the doses of 15 and 25 J/cm2 (Mann-Whitney; p < 0.05). Higher ALP activity was obtained with 5% FBS when the cells were irradiated with doses of 2 and 10 J/cm2. For the dose of 25 J/cm2, the highest ALP activity was observed with 10% FBS. It was concluded that the LLLT parameters used in this study stimulated the metabolic activity of the MDPC-23 cells, especially at the doses of 15 and 25 J/cm2.

Joint minimization of uplink and downlink whole-body exposure dose in indoor wireless networks.

PubMed

Plets, D; Joseph, W; Vanhecke, K; Vermeeren, G; Wiart, J; Aerts, S; Varsier, N; Martens, L

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism.

Joint Minimization of Uplink and Downlink Whole-Body Exposure Dose in Indoor Wireless Networks

PubMed Central

Plets, D.; Joseph, W.; Vanhecke, K.; Vermeeren, G.; Wiart, J.; Aerts, S.; Varsier, N.; Martens, L.

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism. PMID:25793213

The effect of aspirin dosing on platelet function in diabetic and nondiabetic patients: an analysis from the aspirin-induced platelet effect (ASPECT) study.

PubMed

DiChiara, Joseph; Bliden, Kevin P; Tantry, Udaya S; Hamed, Miruais S; Antonino, Mark J; Suarez, Thomas A; Bailon, Oscar; Singla, Anand; Gurbel, Paul A

2007-12-01

Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients. Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients. We examined the effect of aspirin (81, 162, and 325 mg/day for 4 weeks each) on platelet aspirin responsiveness in 120 stable outpatients (30 diabetic patients and 90 nondiabetic patients) with coronary artery disease (CAD) using light transmittance aggregometry (LTA), VerifyNow, platelet function analyzer (PFA)-100, and levels of urinary 11-dehydro-thromboxane B(2) (11-dh-TxB(2)). In the total group, a low prevalence (0-2%) of aspirin resistance was observed with all aspirin doses as determined by arachidonic acid-induced LTA. Aspirin resistance was higher at the 81-mg dose in diabetic versus nondiabetic patients using collagen-induced LTA (27 vs. 4%, P = 0.001), VerifyNow (13 vs. 3%, P = 0.05), and urinary 11-dh-TxB(2) (37 vs. 17%, P = 0.03). Diabetic patients treated with 81 mg exhibited higher platelet function measured by VerifyNow, collagen- and ADP-induced LTA, and 11-dh-TxB(2) levels (P

Improvements to image quality using hybrid and model-based iterative reconstructions: a phantom study.

PubMed

Aurumskjöld, Marie-Louise; Ydström, Kristina; Tingberg, Anders; Söderberg, Marcus

2017-01-01

The number of computed tomography (CT) examinations is increasing and leading to an increase in total patient exposure. It is therefore important to optimize CT scan imaging conditions in order to reduce the radiation dose. The introduction of iterative reconstruction methods has enabled an improvement in image quality and a reduction in radiation dose. To investigate how image quality depends on reconstruction method and to discuss patient dose reduction resulting from the use of hybrid and model-based iterative reconstruction. An image quality phantom (Catphan® 600) and an anthropomorphic torso phantom were examined on a Philips Brilliance iCT. The image quality was evaluated in terms of CT numbers, noise, noise power spectra (NPS), contrast-to-noise ratio (CNR), low-contrast resolution, and spatial resolution for different scan parameters and dose levels. The images were reconstructed using filtered back projection (FBP) and different settings of hybrid (iDose 4 ) and model-based (IMR) iterative reconstruction methods. iDose 4 decreased the noise by 15-45% compared with FBP depending on the level of iDose 4 . The IMR reduced the noise even further, by 60-75% compared to FBP. The results are independent of dose. The NPS showed changes in the noise distribution for different reconstruction methods. The low-contrast resolution and CNR were improved with iDose 4 , and the improvement was even greater with IMR. There is great potential to reduce noise and thereby improve image quality by using hybrid or, in particular, model-based iterative reconstruction methods, or to lower radiation dose and maintain image quality. © The Foundation Acta Radiologica 2016.

Does the choice of mobile C-arms lead to a reduction of the intraoperative radiation dose?

PubMed

Richter, P H; Steinbrener, J; Schicho, A; Gebhard, F

2016-08-01

Mobile C-arm imaging is commonly used in operating rooms worldwide. Especially in orthopaedic surgery, intraoperative C-arms are used on a daily basis. Because of new minimally-invasive surgical procedures a development in intraoperative imaging is required. The purpose of this article is investigate if the choice of mobile C-arms with flat panel detector technology (Siemens Cios Alpha and Ziehm Vision RFD) influences image quality and dose using standard, commercially available test devices. For a total of four clinical application settings, two zoom formats, and all dose levels provided, the transmission dose was measured and representative images were recorded for each test device. The data was scored by four observers to assess low contrast and spatial resolution performance. The results were converted to a relative image quality figure allowing for a direct image quality and dose comparison of the two systems. For one test device, the Cios Alpha system achieved equivalent (within the inter-observer standard error) or better low contrast resolution scores at significantly lower dose levels, while the results of the other test device suggested that both systems achieved similar image quality at the same dose. The Cios Alpha system achieved equivalent or better spatial resolution at significantly lower dose for all application settings except for Cardiac, where a comparable spatial resolution was achieved at the same dose. The correct choice of a mobile C-arm is very important, because it can lead to a reduction of the intraoperative radiation dose without negative effects on image quality. This can be a big advantage to reduce intraoperative radiation not only for the patient but also for the entire OR-team. Copyright © 2016. Published by Elsevier Ltd.

Immunogenicity study to investigate the interchangeability among three different types of polio vaccine: A cohort study in Japan.

PubMed

Ohfuji, Satoko; Ito, Kazuya; Ishibashi, Motoki; Shindo, Shizuo; Takasaki, Yoshio; Yokoyama, Takashi; Yokoyama, Takato; Yamashita, Yuji; Shibao, Keigo; Nakano, Takashi; Tsuru, Tomomi; Irie, Shin; Hirota, Yoshio

2017-06-01

In Japan, the routine immunization program with oral polio vaccine (OPV) has been suspended since September 2012, when a program with 4 doses of inactivated monovalent polio vaccine (IPV) or quadrivalent vaccine against diphtheria, pertussis, and tetanus with IPV (DTaP-IPV) was introduced. The aim of this study was to examine the interchangeability among these 3 types of polio vaccines.We conducted a prospective cohort study at 5 pediatric clinics in Japan. A total of 153 infants were assigned to 1 of the 4 groups by considering the vaccination history of OPV and trivalent vaccine against DTaP. Eleven infants with a history of OPV received 3 doses of DTaP-IPV; 49 infants with a history of OPV and DTaP received 3 doses of IPV; 50 polio vaccine-naïve infants received 2 doses of IPV followed by 2 doses of DTaP-IPV; and 43 polio vaccine-naive infants received 2 doses of DTaP-IPV followed by IPV. The immunogenicity after polio vaccination was evaluated among these 4 groups.After 2 doses of polio vaccination, more than 80% of the infants exhibited a neutralization antibody titer ≥1:8 for all Sabin strains and wild strains in all groups. After the third dose, the seroprotection proportion (i.e., a neutralization antibody titer ≥1:8) reached about 100%. After the fourth dose, a neutralization antibody titer exceeded the required protective levels (i.e., a neutralization antibody titer ≥1:8) considerably in all groups.Four doses of polio vaccines induced a sufficient level of immunity in Japanese infants, irrespective of vaccine combinations or order.

[Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].

PubMed

Ding, Xiao-shuang; Liang, Ai-hua; Wang, Jin-hua; Xiao, Yong-qing; Wu, Zi-lun; Li, Chun-ying; Li, Li; He, Rong; Hui, Lian-qiang; Liu, Bao-yan

2005-07-01

The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined. A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice. LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA. GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.

Protective effects and mechanisms of total alkaloids of Rubus alceaefolius Poir on non‑alcoholic fatty liver disease in rats.

PubMed

Zheng, Haiyin; Zhao, Jinyan; Zheng, Yuqing; Wu, Juan; Liu, Yan; Peng, Jun; Hong, Zhenfeng

2014-10-01

The plant Rubus alceaefolius Poir is used as a hepatic protectant in Traditional Chinese Medicine. The aim of the present study was to confirm the protective effect of the total alkaloids of Rubus alceaefolius Poir (TARAP) on the liver and to evaluate the potential molecular mechanisms associated with adipocytokines underlying non-alcoholic fatty liver disease (NAFLD) in rats. To generate the NAFLD model, Sprague-Dawley rats were administered a high‑fat diet and following 12 weeks of model construction, rats were orally treated with a positive control drug and different doses of TARAP daily for 28 days. The rats were then sacrificed and the livers were collected to evaluate the liver index (LI) and observe histological changes by hematoxylin and eosin (H&E) staining. The secretion levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined by ELISA. Finally, the expression levels of leptin (LEP), resistin and adiponectin (APN) in liver tissues were determined by immunohistochemistry (IHC). The results demonstrated that, in the group treated with methionine and choline bitartrate tablets and in the groups treated with different doses of TARAP, there was a significant reduction in the LI (P<0.05 or P<0.01), a downregulation of the secretion levels of ALT and AST, reduced levels of LEP and resistin and an increased expression of APN in the liver of NAFLD rats compared with the model group. Furthermore, the effect of TARAP treatment of NAFLD rats was dose dependent. In conclusion, TARAP is a potential agent for downregulating LEP and resistin and upregulating APN expression in rats with NAFLD. Furthermore, TARAP may be a potential candidate for improving treatment responses in patients with NAFLD.

Febuxostat ameliorates doxorubicin-induced cardiotoxicity in rats.

PubMed

Krishnamurthy, Bhaskar; Rani, Neha; Bharti, Saurabh; Golechha, Mahaveer; Bhatia, Jagriti; Nag, Tapas Chandra; Ray, Ruma; Arava, Sudheer; Arya, Dharamvir Singh

2015-07-25

The clinical use of doxorubicin is associated with dose limiting cardiotoxicity. This is a manifestation of free radical production triggered by doxorubicin. Therefore, we evaluated the efficacy of febuxostat, a xanthine oxidase inhibitor and antioxidant, in blocking cardiotoxicity associated with doxorubicin in rats. Male albino Wistar rats were divided into four groups: control (normal saline 2.5mL/kg/dayi.p. on alternate days, a total of 6 doses); Doxorubicin (2.5mg/kg/dayi.p. on alternate days, a total of 6 doses), Doxorubicin+Febuxostat (10mg/kg/day oral) and Doxorubicin+Carvedilol (30mg/kg/day oral) for 14days. Febuxostat significantly ameliorated the doxorubicin-induced deranged cardiac functions as there was significant improvement in arterial pressures, left ventricular end diastolic pressure and inotropic and lusitropic states of the myocardium. These changes were well substantiated with biochemical findings, wherein febuxostat prevented the depletion of non-protein sulfhydryls level, with increased manganese superoxide dismutase level and reduced cardiac injury markers (creatine kinase-MB and B-type natriuretic peptide levels) and thiobarbituric acid reactive substances level. Febuxostat also exhibited significant anti-inflammatory (decreased expression of NF-κBp65, IKK-β and TNF-α) and anti-apoptotic effect (increased Bcl-2 expression and decreased Bax and caspase-3 expression and TUNEL positivity). Hematoxylin and Eosin, Masson Trichome, Picro Sirius Red and ultrastructural studies further corroborated with hemodynamic and biochemical findings showing that febuxostat mitigated doxorubicin-induced increases in inflammatory cells, edema, collagen deposition, interstitial fibrosis, perivascular fibrosis and mitochondrial damage and better preservation of myocardial architecture. In addition, all these changes were comparable to those produced by carvedilol. Thus, our results suggest that the antioxidant and anti-apoptotic effect of febuxostat contributes to its protective effects against doxorubicin-induced cardiotoxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In vitro gas production of foliage from three browse tree species treated with different dose levels of exogenous fibrolytic enzymes.

PubMed

López, D; Vázquez-Armijo, J F; López-Villalobos, N; Lee-Rangel, H A; Salem, A Z M; Borquez-Gastelum, J L; Domínguez-Vara, I A; Rojo-Rubio, R

2016-10-01

The aim of this study was to evaluate the effect of different dose levels of exogenous fibrolytic enzymes (EFE) on in vitro ruminal fermentation kinetics and energy utilization of foliages from three browse trees (Pithecellobium dulce, Heliocarpus velutinus and Guazuma ulmifolia). Mixture of EFE product was added to the leaves of the three browse tree species at three dose levels: 0 (control), 3.5 and 7.0 mg/g of DM. Chemical composition of the foliages, including plant secondary metabolites such as total phenolics (TP), saponins (SAP) and aqueous fraction (AF), was determined. In addition, in vitro assaying of ruminal gas production kinetics was determined for the three browse three foliages treated with EFE. P. dulce had the highest crude protein content (p < 0.05), whereas G. ulmifolia had the highest content of neutral detergent fibre and SAP (p < 0.05) and H. velutinus had the lowest content of TP (p < 0.05). The interaction between tree species and dose level of EFE was significant (p < 0.05) for gas production (GP) at 24 h of incubation, parameters b and c of the accumulated GP curve, short-chain fatty acids (SCFA) and metabolizable energy (ME). The lowest (p < 0.01) extent of accumulated GP as well as the b and c values occurred in G. ulmifolia at 0 mg EFE/g DM. P. dulce had the highest (p < 0.05) values for ME and SCFA at the highest dose of EFE. Tree species and dose level had significant (p < 0.05) effects on all parameters describing in vitro ruminal fermentation kinetics and energy utilization. Addition of EFE improved the fermentation kinetics of the browse species considered in this study. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

A comparative analysis of 3D conformal deep inspiratory–breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer

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

Reardon, Kelli A.; Read, Paul W.; Morris, Monica M.

2013-07-01

Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory–breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumesmore » of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.« less

External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

NASA Astrophysics Data System (ADS)

Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

2009-01-01

Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

Gamma Radiation Dose Rate in Air due to Terrestrial Radionuclides in Southern Brazil: Synthesis by Geological Units and Lithotypes Covered by the Serra do Mar Sul Aero-Geophysical Project

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

Bastos, Rodrigo O.; Appoloni, Carlos R.; Pinese, Jose P. P.

2008-08-07

The absorbed dose rates in air due to terrestrial radionuclides were estimated from aerial gamma spectrometric data for an area of 48,600 km{sup 2} in Southern Brazil. The source data was the Serra do Mar Sul Aero-Geophysical Project back-calibrated in a cooperative work among the Geological Survey of Brazil, the Geological Survey of Canada, and Paterson, Grant and Watson Ltd. The concentrations of eU (ppm), eTh (ppm) and K (%) were converted to dose rates in air (nGy{center_dot}h{sup -1}) by accounting for the contribution of each element's concentration. Regional variation was interpreted according to lithotypes and a synthesis was performedmore » according to the basic geological units present in the area. Higher values of total dose were estimated for felsic igneous and metamorphic rocks, with average values varying up to 119{+-}24 nGy{center_dot}h{sup -1}, obtained by Anitapolis syenite body. Sedimentary, metasedimentary and metamafic rocks presented the lower dose levels, and some beach deposits reached the lowest average total dose, 18.5{+-}8.2 nGy{center_dot}h{sup -1}. Thorium gives the main average contribution in all geological units, the highest value being reached by the nebulitic gneisses of Atuba Complex, 71{+-}23 nGy{center_dot}h{sup -1}. Potassium presents the lowest average contribution to dose rate in 53 of the 72 units analyzed, the highest contribution being obtained by intrusive alkaline bodies (28{+-}12 nGy{center_dot}h{sup -1}). The general pattern of geographic dose distribution respects well the hypotheses on geo-physicochemical behavior of radioactive elements.« less

Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants.

PubMed

Tekgündüz, Kadir Şerafettin; Ceviz, Naci; Caner, İbrahim; Olgun, Haşim; Demirelli, Yaşar; Yolcu, Canan; Şahin, İrfan Oğuz; Kara, Mustafa

2015-08-01

Haemodynamically significant patent ductus arteriosus is a significant cause of morbidity and mortality in pre-term infants. This retrospective study was conducted to investigate the usefulness of lower-dose paracetamol for the treatment of patent ductus arteriosus in pre-term infants. A total of 13 pre-term infants who received intravenous paracetamol because of contrindications or side effects to oral ibuprofen were retrospectively enrolled. In the first patient, the dose regimen was 15 mg/kg/dose, every 6 hours. As the patient developed significant elevation in transaminase levels, the dose was decreased to 10 mg/kg/dose, every 8 hours in the following 12 patients. Echocardiographic examination was conducted daily. In case of closure, it was repeated after 2 days and when needed thereafter in terms of reopening. A total of 13 patients received intravenous paracetamol. Median gestational age was 29 weeks ranging from 24 to 31 weeks and birth weight was 950 g ranging from 470 to 1390 g. The median postnatal age at the first intravenous paracetamol dose was 3 days ranging from 2 to 9 days. In 10 of the 13 patients (76.9%), patent ductus arteriosus was closed at the median 2nd day of intravenous paracetamol ranging from 1 to 4 days. When the patient who developed hepatotoxicity was eliminated, the closure rate was found to be 83.3% (10/12). Intravenous paracetamol may be a useful treatment option for the treatment of patent ductus arteriosus in pre-term infants with contrindication to ibuprofen. In our experience, lower-dose paracetamol is effective in closing the patent ductus arteriosus in 83.3% of the cases.

Reproductive Alterations in Chronically Exposed Female Mice to Environmentally Relevant Doses of a Mixture of Phthalates and Alkylphenols.

PubMed

Patiño-García, Daniel; Cruz-Fernandes, Leonor; Buñay, Julio; Palomino, Jaime; Moreno, Ricardo D

2018-02-01

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that modify hormone biosynthesis, causing adverse effects to human health. Among them, phthalates and alkylphenols are important due to their wide use in plastics, detergents, personal care products, cosmetics, and food packaging. However, their conjoint effects over reproductive female health have not been addressed. The aim of this work was to test the effect of chronically exposed female mice to a mixture of three phthalates [bis (2-ethylhexyl), dibutyl, and benzyl butyl] and two alkylphenols (4-nonylphenol and 4-tert-octylphenol) from conception to adulthood at environmentally relevant doses. These EDCs were administered in two doses: one below the minimal risk dose to cause adverse effects on human development and reproduction [1 mg/kg body weight (BW)/d of the total mixture] and the other one based on the reference value close to occupational exposure in humans (10 mg/kg BW/d of the total mixture). Our results show that both doses had similar effects regarding the uterus and ovary relative weight, estrous cyclicity, serum levels of progesterone and 17β-estradiol, and expression of key elements in the steroidogenesis pathway (acute steroidogenic regulatory protein and CYP19A1). However, only the 1-mg/kg BW/d dose delayed the onset of puberty and the transition from preantral to antral follicles, whereas the 10-mg/kg BW/d dose decreased the number of antral follicles and gonadotropin receptor expression. In addition, we observed changes in several fertility parameters in exposed females and in their progeny (F2 generation). In conclusion, our results indicate that chronic exposure to a complex EDC mixture, at environmentally relevant doses, modifies reproductive parameters in female mice. Copyright © 2018 Endocrine Society.

Importance of a Patient Dosimetry and Clinical Follow-up Program in the Detection of Radiodermatitis After Long Percutaneous Coronary Interventions

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

Vano, Eliseo, E-mail: eliseov@med.ucm.es; Escaned, Javier; Vano-Galvan, Sergio

Complex percutaneous interventions often require high radiation doses likely to produce skin radiation injuries. We assessed the methodology used to select patients with potential skin injuries in cardiac procedures and in need of clinical follow-up. We evaluated peak skin dose and clinical follow-up in a case of radiodermatitis produced during a total occlusion recanalization. This prospective study followed CIRSE and ACC/AHA/SCAI recommendations for patient radiation dose management in interventional procedures carried out in a university hospital with a workload of 4200 interventional cardiac procedures per year. Patient dose reports were automatically transferred to a central database. Patients exceeding trigger levelsmore » for air kerma area product (500 Gy cm{sup 2}) and cumulative skin dose (5 Gy) were counseled and underwent follow-up for early detection of skin injuries, with dermatologic support. The Ethical Committee and the Quality Assurance and Radiation Safety Committee approved the program. During 2010, a total of 13 patients (3.0/1,000 that year) received dose values exceeding trigger levels in the cardiovascular institute. Only one patient, who had undergone two consecutive procedures resulting in 970 Gy cm{sup 2} and 13.0 Gy as cumulative skin dose, showed signs of serious radiodermatitis that resolved in 3.7 months. The remaining patients did not manifest skin lesions during follow-up, and whenever patient examination was not feasible as part of the follow-up, neither patients nor families reported any skin injuries. Peak skin dose calculation and close clinical follow-up were feasible and appropriate, with a moderate additional workload for the staff and satisfaction for the patient.« less

Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with acute coronary syndrome: A systematic review and meta-analysis

PubMed Central

Su, Qiang; Guo, Wenqin; Dai, Weiran; Li, Hongqing; Yang, Huafeng; Li, Lang

2017-01-01

Background Acute coronary syndrome (ACS) is an important disease threatening human life and health. Many studies have shown that the loading dose of atorvastatin can significantly improve the prognosis of patients with ACS, and reduce the mortality. However, this conclusion is not consistent. Thus, we aimed to evaluate the effect of high-dose rosuvastatin loading before percutaneous coronary intervention (PCI) in Chinese patients with ACS using a meta-analysis based on a systematic review of published articles. Methods We systematically reviewed published studies, evaluating the effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with ACS. The retrieval time is limited from inception to 2 November 2016, and the retrieved databases included PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, the VIP database and the Wang Fang database. Two researchers independently assessed the quality of the included studies and then extracted the data. Stata 11.0 was used for data analysis. Results In total, 11 articles, which included 802 patients, were included in our meta-analysis. Among these patients, 398 patients were in the high-dose group (20 mg/day) and 404 patients were in the conventional dose group (10 mg/day). Meta-analysis results showed that compared with the conventional dose group: 1) The loading dose of rosuvastatin can significantly reduce the hs-CRP level after PCI, including at 24 hours (SMD = -0.65, 95%CI -0.84 ~ -0.47, P = 0.000), 48 hours (SMD = -0.40, 95%CI -0.68 ~ -0.11, P = 0.006), and four weeks (SMD = -1.64, 95%CI -2.01 ~ -1.26, P = 0.000). 2) The loading dose of rosuvastatin can significantly reduce the levels of LDL-C and cTnT, including the level of LDL-C at 30 d after PCI (SMD = -0.89, 95%CI -1.10 ~ -0.69, P = 0.000), and the level of cTnT at 24 h after PCI (SMD = -1.93, 95%CI -2.28 ~ -1.59, P = 0.000), and increase the level of HDL-C at 48 h after PCI (SMD = 0.61, 95%CI 0.34 ~ 0.88, P = 0.000). 3) The loading dose of rosuvastatin can significantly reduce the levels of TG and TC, including the level of TG at 30 d after PCI (SMD = -0.94, 95%CI -1.17 ~ -0.71, P = 0.000), the level of TC at 48 h after PCI (SMD = -0.35, 95%CI -0.68 ~ -0.01, P = 0.043), and the level of TC at 30 d after PCI (SMD = -0.77, 95%CI -0.98 ~ -0.56, P = 0.000). Conclusions Our systematic review and meta-analysis showed that, compared with the conventional dose, the loading dose of rosuvastatin was more beneficial to patients with ACS in China and is suitable for clinical application. Due to the limitations of the quality and quantity of included articles, this conclusion still needs to be confirmed by multicenter clinical trials. PMID:28231287

Effects of soybean agglutinin on intestinal barrier permeability and tight junction protein expression in weaned piglets.

PubMed

Zhao, Yuan; Qin, Guixin; Sun, Zewei; Che, Dongsheng; Bao, Nan; Zhang, Xiaodong

2011-01-01

This study was developed to provide further information on the intestinal barrier permeability and the tight junction protein expression in weaned piglets fed with different levels of soybean agglutinin (SBA). Twenty-five weaned crossbred barrows (Duroc × Landrace × Yorkshire) were selected and randomly allotted to five groups, each group with five replicates. The piglets in the control group were not fed with leguminous products. 0.05, 0.1, 0.15 and 0.2% SBA was added to the control diet to form four experimental diets, respectively. After the experimental period of 7 days (for each group), all the piglets were anesthetized with excess procaine and slaughtered. The d-lactic acid in plasma and the Ileal mucosa diamine oxidase (DAO) was analyzed to observe the change in the intestinal permeability. The tight junction proteins occludin and ZO-1 in the jejunum tissue distribution and relative expression were detected by immunohistochemistry and Western Blot. The results illustrated that a high dose of SBA (0.1-0.2%) could increase the intestinal permeability and reduce piglet intestinal epithelial tight junction protein occludin or ZO-1 expression, while low dose of SBA (0.05% of total diet) had no significant affects. The contents of DAO, d-lactic acid, occludin or ZO-1, had a linear relationship with the SBA levels (0-0.2%) in diets. The high dose SBA (0.1-0.2%) could increase the intestinal permeability and reduce piglet intestinal epithelial tight junction protein occludin or ZO-1 expression, while low dose of SBA (0.05% of total diet) had no affects.

Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients

PubMed Central

Peng, Xiang; Zhi, Min; Wei, Ming; Li, Ting-Ting; Zhang, Min; Zhang, Yuan-Qi; He, Huan; Su, Mingli; Wang, Wei; Chen, Jun-rong; Tang, Jian; Gao, Xiang; Hu, Pin-Jin; Liang, Xiao-Yan

2017-01-01

Abstract The effectiveness of thalidomide in treating inflammatory bowel disease (IBD) has been widely recognized. Meanwhile, many serious adverse drug reactions have been observed, but no know reports on ovarian reserve function. Female patients, ranging in age between 18 and 40, were referred to our institution to undergo sex hormone detection and ultrasonic scanning for ovarian function assessment, between February 1, 2016 and September 31, 2016. Thirty-three patients treated with thalidomide (group A), 73 patients without thalidomide (group B), and 78 healthy women as control were studied. Menstrual disorder was higher in group A than group B (78.8% vs 57.2%, P < 0.05), and both groups were higher than control group 33.3%, P < 0.05. Anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) in group A were lower than group B, P < 0.05, while estradiol (E2) and follicle-stimulating hormone (FSH) levels were no different between 2 groups. Crohn Disease Endoscopic Index of Severity (CDEIS) and thalidomide were the independent risk factors in diminished ovarian reserve (DOR), and when dose reached 75 mg/day, 5 g total, or when treatment time reached 10 months respectively. These influence may increasing (P < 0.05), but they may recover after stopping (P < 0.05). Thalidomide was an independent risk factor leading to DOR in female IBD patients, the influence may increasing when daily dose and accumulated dose reached 75 mg/day and 5 g total dose, but may be reversed by stopping. PMID:28538364

Evaluation of the Safety, Tolerability, and Pharmacokinetics of Gammaplex® 10% Versus Gammaplex® 5% in Subjects with Primary Immunodeficiency.

PubMed

Wasserman, Richard L; Melamed, Isaac R; Stein, Mark R; Jolles, Stephen; Norton, Miranda; Moy, James N

2017-04-01

This phase 3, multicenter, open-label, randomized, two-period, crossover bioequivalence trial evaluated the safety, tolerability, and pharmacokinetics of intravenous immunoglobulins (IVIGs) Gammaplex 5% and Gammaplex 10% in 33 adults and 15 children with primary immunodeficiency diseases (PIDs). Eligible adults received five Gammaplex 5% infusions followed by five Gammaplex 10% infusions, or vice versa, stratified by a 21- or 28-day dosing regimen. Pediatric subjects received five Gammaplex 10% infusions only. The primary objective, to demonstrate the bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval, was met based on the Gammaplex 10%/Gammaplex 5% ratio of area under the concentration versus time curve (AUC 0-28 ) values. Throughout the study, total immunoglobulin G trough levels were well maintained, with total values generally ≥600 mg/dL (minimum level for study inclusion). At the dosing schedules and infusion rates used in this study, safety and tolerability were comparable and acceptable in adult and pediatric PID subjects treated with Gammaplex 10% and 5%. In this study, the first direct comparison of 5% IVIG and 10% IVIG products in PID subjects, the pharmacokinetic analysis demonstrated bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval. The Gammaplex 10% formulation was safe and well tolerated in pediatric and adult PID subjects. Based on the results from this bridging study in PID subjects, Gammaplex 10% could be expected to have a therapeutic effect similar to the licensed Gammaplex 5%, which has demonstrated efficacy and tolerability in patients with PID and idiopathic thrombocytopenic purpura.

Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).

PubMed

Gollins, S W; Myint, S; Susnerwala, S; Haylock, B; Wise, M; Topham, C; Samuel, L; Swindell, R; Morris, J; Mason, L; Levine, E

2009-09-15

The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (< or =1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m(-2) b.i.d. and irinotecan 50 mg m(-2); Dose level 2: capecitabine 650 mg m(-2) b.i.d. and irinotecan 60 mg m(-2); Dose level 3: capecitabine 825 mg m(-2) b.i.d. and irinotecan 60 mg m(2); Dose level 4: capecitabine 825 mg m(-2) b.i.d. and irinotecan 70 mg m(-2). Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as < or =1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%. In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m(-2) b.i.d. days 1-35 and weekly IV irinotecan at 60 mg m(-2) weeks 1-4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates.

BOOK REVIEW: NCRP Report No. 160: Ionizing Radiation Exposure of the Population of the United States NCRP Report No. 160: Ionizing Radiation Exposure of the Population of the United States

NASA Astrophysics Data System (ADS)

Thurston, Jim

2010-10-01

This report by Committee 6 of the Council is an extensive update of a previous report on the exposure of the US population to ionizing radiation sources from data gathered in the 1980s (published as Report 93 in 1987). It is combined with an update on the more in-depth assessment of data on medical exposures previously reported in 1989 (Report 100). Individual chapters in this new report are dedicated to specific sources of exposure to the US population—both from natural and artificial radiation—and the level of detail in each chapter is intended to reflect the significance of the contribution of each source to the total collective dose of the population. The first chapter is on the most significant contributor: background radiation. It expands on the concept of natural background radiation in Report 93, renaming it 'ubiquitous background', and describing in detail the contributions from both extra-terrestrial and terrestrial sources. The data demonstrates that the average dose from such exposure has varied little since the previous report (a slight increase from 3.0 mSv to 3.1 mSv). The next chapter is on medical radiation, i.e. the exposure to the population when attending as patients, not including occupational exposure to hospital workers. The most striking data published in the entire report is the increase in the contribution to the total US population dose attributed to such medical exposures. It is now as significant as that from background radiation: medical exposures now account for an average effective dose to the US citizen of 3.00 mSv, up from 0.53 mSv in 1992 (Report 100). The most important contribution to this increase is the 1.46 mSv from CT scanning alone. The nuclear medicine (including PET) contribution is up from 0.14 mSv to 0.77mSv. This evidently must be due to significant changes in medical radiological practice in the US tied to the increase in the availability of CT and PET imaging facilities. These increasing contributions have driven the overall average effective dose to a US citizen from approximately 3.6 mSv reported in 1987 to 6.2 mSv per annum, with medical exposures now responsible for 48% of the total (up from 15% in 1992). It is interesting to note that over roughly the same period of time, the total dose to the UK population has been revised upwards from 2.6 mSv to 2.7mSv to reflect (amongst other factors) the increase in CT scanning in the UK—obviously a much smaller change. However, one has to consider whether medical radiological practices in the UK might similarly change in the coming years, and UK population doses subsequently follow the US trend reported here. There is now a more detailed chapter on exposure to the population from consumer products and activities. Of the contributing factors in this category, the radiation dose received from radioactivity in tobacco smoke is the most significant, followed by building materials and air travel. There has been no significant change in the total dose received from these sources when compared to the earlier Report 93, at 0.13 mSv. The report also gives significant detail on exposure to the public from industrial sources (not just nuclear power), and discusses occupational exposure. Both these categories of exposure, averaged out of the whole population, give very small contributions to the total dose (0.003 mSv and 0.005 mSv, respectively). There are two final points to make about this report. Firstly, it continues the NCRP policy introduced for Report 93 of using SI units rather than the radiation units more commonly used within the US, hence making this report more readily accessible to an international audience. Secondly, in all the descriptions of the exposures and radiation doses received, no attempt is made to convert the doses into risk. The view of the Council, as stated in the forward to the report, is that attempting to quantify the risks associated with such levels of radiation exposure falls outside the remit of the Committee that prepared the report.

Low Dose CT Reconstruction via Edge-preserving Total Variation Regularization

PubMed Central

Tian, Zhen; Jia, Xun; Yuan, Kehong; Pan, Tinsu; Jiang, Steve B.

2014-01-01

High radiation dose in CT scans increases a lifetime risk of cancer and has become a major clinical concern. Recently, iterative reconstruction algorithms with Total Variation (TV) regularization have been developed to reconstruct CT images from highly undersampled data acquired at low mAs levels in order to reduce the imaging dose. Nonetheless, the low contrast structures tend to be smoothed out by the TV regularization, posing a great challenge for the TV method. To solve this problem, in this work we develop an iterative CT reconstruction algorithm with edge-preserving TV regularization to reconstruct CT images from highly undersampled data obtained at low mAs levels. The CT image is reconstructed by minimizing an energy consisting of an edge-preserving TV norm and a data fidelity term posed by the x-ray projections. The edge-preserving TV term is proposed to preferentially perform smoothing only on non-edge part of the image in order to better preserve the edges, which is realized by introducing a penalty weight to the original total variation norm. During the reconstruction process, the pixels at edges would be gradually identified and given small penalty weight. Our iterative algorithm is implemented on GPU to improve its speed. We test our reconstruction algorithm on a digital NCAT phantom, a physical chest phantom, and a Catphan phantom. Reconstruction results from a conventional FBP algorithm and a TV regularization method without edge preserving penalty are also presented for comparison purpose. The experimental results illustrate that both TV-based algorithm and our edge-preserving TV algorithm outperform the conventional FBP algorithm in suppressing the streaking artifacts and image noise under the low dose context. Our edge-preserving algorithm is superior to the TV-based algorithm in that it can preserve more information of low contrast structures and therefore maintain acceptable spatial resolution. PMID:21860076

Special features of total knee replacement in hemophilia.

PubMed

Rodriguez-Merchan, Emerito Carlos

2013-12-01

Total knee replacement is an operation frequently needed by hemophilia patients, which greatly improves their quality of life. This operation, however, carries a higher risk of bleeding and infection for hemophiliacs than it does for osteoarthritis sufferers. It is advisable to implant prosthetic components using antibiotic-loaded cement. It is essential to maintain a level of 100% of the replacement clotting factor for 2 weeks. Hematological treatment must be established, depending on the patient's factor levels and other pharmacokinetic parameters such as recovery and half-life, optimal doses and treatment time. It is preferable to use general anesthesia due to the risk of spinal bleeding. The lifespan of total knee replacement in hemophilic patients is shorter than in patients with osteoarthritis because of the increased risk of infection.

Engineering cord blood to improve engraftment after cord blood transplant

PubMed Central

Dave, Hema; Bollard, Catherine M.; Shpall, Elizabeth J.

2017-01-01

Umbilical cord blood transplant (CBT) has traditionally been associated with slower engraftment of neutrophils, delayed immune reconstitution and consequently higher risk of infections as compared with peripheral blood progenitor cell (PBPC) or bone marrow (BM) transplants. This is primarily due to low numbers of total nucleated cells (TNCs) and the naive nature of CB immune cells. The use of double unit CB transplant (DCBT) increases the total cell dose in the graft, but it still does not produce as rapid engraftment as seen with PBPC or even BM transplants. Herein, we discuss strategies to improve engraftment after CBT. We describe methods of (I) expansion of CB graft ex vivo to increase the total cell dose; and (II) enhancement of BM homing capability of CB progenitor cells; (III) ex vivo expansion of CB derived T cells for improving T cell function against viruses, tumors and protection from graft versus host disease (GVHD). With these novel approaches, engraftment after CBT is now reaching levels comparable to that of other graft types. PMID:28607915

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy.

PubMed

Kobashi, Keiji; Prayongrat, Anussara; Kimoto, Takuya; Toramatsu, Chie; Dekura, Yasuhiro; Katoh, Norio; Shimizu, Shinichi; Ito, Yoichi M; Shirato, Hiroki

2018-03-01

Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold.

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy

PubMed Central

Kobashi, Keiji; Kimoto, Takuya; Toramatsu, Chie; Dekura, Yasuhiro; Katoh, Norio; Shimizu, Shinichi; Ito, Yoichi M; Shirato, Hiroki

2018-01-01

Abstract Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance–covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold. PMID:29538699

The safety of green tea and green tea extract consumption in adults - Results of a systematic review.

PubMed

Hu, Jiang; Webster, Donna; Cao, Joyce; Shao, Andrew

2018-06-01

A systematic review of published toxicology and human intervention studies was performed to characterize potential hazards associated with consumption of green tea and its preparations. A review of toxicological evidence from laboratory studies revealed the liver as the target organ and hepatotoxicity as the critical effect, which was strongly associated with certain dosing conditions (e.g. bolus dose via gavage, fasting), and positively correlated with total catechin and epigallocatechingallate (EGCG) content. A review of adverse event (AE) data from 159 human intervention studies yielded findings consistent with toxicological evidence in that a limited range of concentrated, catechin-rich green tea preparations resulted in hepatic AEs in a dose-dependent manner when ingested in large bolus doses, but not when consumed as brewed tea or extracts in beverages or as part of food. Toxico- and pharmacokinetic evidence further suggests internal dose of catechins is a key determinant in the occurrence and severity of hepatotoxicity. A safe intake level of 338 mg EGCG/day for adults was derived from toxicological and human safety data for tea preparations ingested as a solid bolus dose. An Observed Safe Level (OSL) of 704 mg EGCG/day might be considered for tea preparations in beverage form based on human AE data. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Immune parameters to p67C antigen adjuvanted with ISA206VG correlate with protection against East Coast fever.

PubMed

Lacasta, Anna; Mwalimu, Stephen; Kibwana, Elisabeth; Saya, Rosemary; Awino, Elias; Njoroge, Thomas; Poole, Jane; Ndiwa, Nicholas; Pelle, Roger; Nene, Vishvanath; Steinaa, Lucilla

2018-03-07

East Coast fever (ECF) is a lymphoproliferative disease caused by the tick-transmitted protozoan parasite Theileria parva. ECF is one of the most serious cattle tick-borne diseases in Sub-Saharan Africa. We have previously demonstrated that three doses of the C-terminal part of the sporozoite protein p67 (p67C) adjuvanted with ISA206VG confers partial protection against ECF at a herd level. We have tested the efficacy of two doses of this experimental vaccine, as reducing the vaccination regimen would facilitate its deployment in the field. We reconfirm that three antigen doses gave a significant level of protection to severe disease (46%, ECF score < 6) when compared with the control group, while two doses did not (23%). Animals receiving three doses of p67C developed higher antibody titers and CD4 + T-cell proliferation indices, than those which received two doses. A new panel of immune parameters were tested in order to identify factors correlating with protection: CD4 + proliferation index, total IgG, IgG1, IgG2 and IgM half maximal titers and neutralization capacity of the sera with and without complement. We show that some of the cellular and humoral immune responses provide preliminary correlates of protection. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Comparative study of the effect of decamethoxine, decamine and levorin on carbohydrate metabolic indices in the liver of white rats].

PubMed

Meshchishetn, I F; Iarmol'chuk, G M

1979-01-01

Intramuscular injection of decamin into the animals in a dose of 0.5 and 1 mg/kg has no significant effect on carbohydrate metabolism in the liver of white rats. Decamethoxin and levorin injected in the same doses, specifically in a dose of 1 mg/kg, reduced the level of glucose as well as that of total and free glycogen in the liver. The drugs lowered also the activity of phosphorylase and glocoso-6-phosphatase. Meanwhile the activity of hexokinase, lactate dehydrogenase and phosphoglucosiomerase was potentiated. The animals given decamethoxin showed the aforesaid parameters returning to normal 20 days after the drug was discontinued, whereas similar changes were not found in the rats on levorin.

Impact of total ionizing dose irradiation on Pt/SrBi2Ta2O9/HfTaO/Si memory capacitors

NASA Astrophysics Data System (ADS)

Yan, S. A.; Zhao, W.; Guo, H. X.; Xiong, Y.; Tang, M. H.; Li, Z.; Xiao, Y. G.; Zhang, W. L.; Ding, H.; Chen, J. W.; Zhou, Y. C.

2015-01-01

In this work, metal-ferroelectric-insulator-semiconductor (MFIS) structure capacitors with SrBi2Ta2O9 (300 nm) as ferroelectric thin film and HfTaO (6 nm, 8 nm, 10 nm, and 12 nm) as insulating buffer layer were proposed and investigated. The prepared capacitors were fabricated and characterized before radiation and then subjected to 60Co gamma irradiation in steps of two dose levels. Significant irradiation-induced degradation of the electrical characteristics was observed. The radiation experimental results indicated that stability and reliability of as-fabricated MFIS capacitors for nonvolatile memory applications could become uncontrollable under strong irradiation dose and/or long irradiation time.

Measurement of (222)Rn concentration levels in drinking water and the associated health effects in the Southern part of West Bank - Palestine.

PubMed

Thabayneh, Khalil M

2015-09-01

Radon concentration and annual effective doses were measured in drinking water in the Southern Part of West Bank - Palestine, by using both passive and active techniques. 184 samples were collected from various sources i.e. tap water, groundwater, rain waters and mineral waters. It is found that the annual effective dose resulting from inhalation and ingestion of radon emanated from all types of drinking water is negligible compared to the total annual effective dose from indoor radon in the region. Results reveal that there is no significant public health risk from radon ingested and inhalation with drinking water in the study region. Copyright © 2015. Published by Elsevier Ltd.

Rejoining and misrejoining of radiation-induced chromatin breaks. I. experiments with human lymphocytes

NASA Technical Reports Server (NTRS)

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

1996-01-01

Fluorescence in situ hybridization with a composite probe for human chromosome 4 and a probe that stained all centromeres was used to study gamma-ray induced breakage, rejoining and misrejoining in prematurely condensed chromosomes in human lymphocytes. Dose-response curves for the induction of all types of aberrations in prematurely condensed human chromosomes 4 were determined immediately after irradiation and after 8 h postirradiation incubation. In addition, aberrations were measured after various incubation times from 0 to 18 h after a dose of 7 Gy. Unrejoined chromosome breaks were the most frequent type of aberration observed immediately after irradiation. Approximately 15% of total aberrations observed were chromosome exchanges. After 8 h postirradiation incubation, the frequency of breaks in prematurely condensed chromosomes declined to about 20% of the initial value, and chromosomal exchanges became the most frequent aberration. Results of metaphase analysis were similar to those for prematurely condensed chromosomes after 8 h incubation with the exception that a significantly lower frequency of fragments was observed. Symmetrical and asymmetrical interchanges were found at similar frequencies at all doses. No complex exchanges were observed in lymphocyte chromosomes immediately after exposure. They accounted for about 1% of total exchanges in metaphase chromosomes at doses <3 Gy and about 14% at 7 Gy. Incomplete exchanges amounted to approximately 15% of total exchanges at all doses. The kinetics of break rejoining was exponential, and the frequency of exchanges increased with kinetics similar to that observed for the rejoining of the breaks. This increase in the total exchanges as a function of the time between irradiation and fusion was due to a rapid increase in reciprocal interchanges, and a slower increase in complex exchanges; the frequency of incomplete exchanges increased initially, then decreased with prolonged incubation to the level observed in metaphase. It is concluded that the formation of each kind of chromosome aberrations follows different kinetics.

Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer.

PubMed

Hsueh, Yu-Mei; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Pu, Yeong-Shiau; Lin, Ying-Chin; Tsai, Cheng-Shiuan; Huang, Chao-Yuan

2017-09-01

This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04-0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06-2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

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

Richter, Daniel; TU Darmstadt, Darmstadt; Saito, Nami

2014-05-01

Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporalmore » correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V{sub 95}) and 107% (V{sub 107}) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V{sub 95} and V{sub 107} values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V{sub 95} > 87%, SD < 3%) and overdose (mean V{sub 107} < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.« less

[Association between urinary polycyclic aromatic hydrocarbon metabolites and elevated serum uric acid levels in coke oven workers].

PubMed

Deng, Siyun; Deng, Qifei; Hu, Die; Li, Jun; Zhu, Xiaoyan; Guo, Huan; Wu, Tangchun

2014-06-01

To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and serum uric acid levels in coke oven workers and to provide new clues to the pathogenic mechanism of PAHs. A total of 1302 coke oven workers were divided into four groups, namely control group and low-, intermediate-, and high-dose exposure groups. The concentrations of ambient PAHs at each workplace were determined by high-performance liquid chromatography. The detailed information on the occupational history and health of workers was collected by questionnaire survey and physical examination, and so were their blood and urine samples. Serum uric acid and creatinine levels were measured using a Hitachi 7020 automatic biochemical analyzer. Ten urinary PAH metabolites were detected by gas chromatography-mass spectrometry. Serum uric acid levels were the highest in the high-dose exposure group, followed by the intermediate- and low-dose exposure groups, and were the lowest in the control group. There were significant correlations between serum uric acid levels and the quartiles of 1-hydroxynaphthalene and 1-hydroxyphenanthrene (P < 0.05). After adjustment for PAH metabolite-related relationship, only urinary 1-hydroxyphenanthrene was significantly correlated with serum uric acid levels (P = 0.001). After adjustment for confounding factors and using the 1st quartile of 1-hydroxyphenanthrene as a reference, the odds ratio for hyperuricemia in subjects with the 2nd, 3rd, and 4th quartiles of 1-hydroxyphenanthrene were 1.55, 1.57, and 2.35, respectively. Urinary 1-hydroxyphenanthrene is associated with a dose-response increase in serum uric acid levels in coke oven workers, and exposure to phenanthrene in PAHs may be a risk factor for hyperuricemia.

Radiation Dose Testing on Juno High Voltage Cables

NASA Technical Reports Server (NTRS)

Green, Nelson W.; Kirkham, Harold; Kim, Wousik; McAlpine, Bill

2008-01-01

The Juno mission to Jupiter will have a highly elliptical orbit taking the spacecraft through the radiation belts surrounding the planet. During these passes through the radiation belts, the spacecraft will be subject to high doses of radiation from energetic electrons and protons with energies ranging from 10 keV to 1 GeV. While shielding within the spacecraft main body will reduce the total absorbed dose to much of the spacecraft electronics, instruments and cables on the outside of the spacecraft will receive much higher levels of absorbed dose. In order to estimate the amount of degradation to two such cables, testing has been performed on two coaxial cables intended to provide high voltages to three of the instruments on Juno. Both cables were placed in a vacuum of 5x10(exp -6) torr and cooled to -50(deg)C prior to exposure to the radiation sources. Measurements of the coaxial capacitance per unit length and partial discharge noise floor indicate that increasing levels of radiation make measurable but acceptably small changes to the F EP Teflon utilized in the construction of these cables. In addition to the radiation dose testing, observations were made on the internal electrostatic charging characteristics of these cables and multiple discharges were recorded.

Radiation Dose Testing on Juno High Voltage Cables

NASA Technical Reports Server (NTRS)

Green, Nelson W.; Kirkham, Harold; Kim, Wousik; McAlpine, Bill

2008-01-01

The Juno mission to Jupiter will have a highly elliptical orbit taking the spacecraft through the radiation belts surrounding the planet. During these passes through the radiation belts, the spacecraft will be subject to high doses of radiation from energetic electrons and protons with energies ranging from 10 keV to 1 GeV. While shielding within the spacecraft main body will reduce the total absorbed dose to much of the spacecraft electronics, instruments and cables on the outside of the spacecraft will receive much higher levels of absorbed dose. In order to estimate the amount of degradation to two such cables, testing has been performed on two coaxial cables intended to provide high voltages to three of the instruments on Juno. Both cables were placed in a vacuum of 5x10-6 torr and cooled to -50 C prior to exposure to the radiation sources. Measurements of the coaxial capacitance per unit length and partial discharge noise floor indicate that increasing levels of radiation make measurable but acceptably small changes to the F EP Teflon utilized in the construction of these cables. In addition to the radiation dose testing, observations were made on the internal electrostatic charging characteristics of these cables and multiple discharges were recorded.

[Changes in gastric function in rats after intragastric introduction of corvitin at high doses].

PubMed

Vovkun, T V; Ianchuk, P I; Shtanova, L Ia; Vesel'skyĭ, S P; Baranovs'kyĭ, V A

2014-01-01

Intragastric administration of corvitin at doses of 10, 20 and 40 mg/kg dose-dependently increased the volume of gastric juice and the total production of hydrochloric acid (HA). Amplification of hexosamines and cysteine production was observed only when the study drug was administered at a dose of 10 mg/kg. When corvitin was used at 20 and 40 mg/kg, these parameters were at the level of control values. Protein production increased in response to 10 and 20 mg/kg corvitin, but fell below the control values after administration of 40 mg/kg of the drug. The level of blood flow in the gastric mucosa increased following administration of 10 mg/kg corvitin, was not different from the baseline after 20 mg/kg of the drug and significantly decreased in response to 40 mg/kg of flavonoid. Our results indicate that a single intragastric application of corvitin at dose of 10 mg/kg activates gastric defense mechanisms. At 20 and 40 mg/kg, corvitin does not affect them but gradually reduces blood flow in gastric mucosa, causes a disturbance of protein synthesis and hypersecretion of HA into the cavity of the stomach, which can lead to disruption of the digestive process and the integrity of gastric mucosa.

Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment for children with sickle cell anemia

PubMed Central

Despotovic, Jenny M.; Mortier, Nicole A.; Flanagan, Jonathan M.; He, Jin; Smeltzer, Matthew P.; Kimble, Amy C.; Aygun, Banu; Wu, Song; Howard, Thad; Sparreboom, Alex

2011-01-01

Hydroxyurea therapy has proven laboratory and clinical efficacies for children with sickle cell anemia (SCA). When administered at maximum tolerated dose (MTD), hydroxyurea increases fetal hemoglobin (HbF) to levels ranging from 10% to 40%. However, interpatient variability of percentage of HbF (%HbF) response is high, MTD itself is variable, and accurate predictors of hydroxyurea responses do not currently exist. HUSTLE (NCT00305175) was designed to provide first-dose pharmacokinetics (PK) data for children with SCA initiating hydroxyurea therapy, to investigate pharmacodynamics (PD) parameters, including HbF response and MTD after standardized dose escalation, and to evaluate pharmacogenetics influences on PK and PD parameters. For 87 children with first-dose PK studies, substantial interpatient variability was observed, plus a novel oral absorption phenotype (rapid or slow) that influenced serum hydroxyurea levels and total hydroxyurea exposure. PD responses in 174 subjects were robust and similar to previous cohorts; %HbF at MTD was best predicted by 5 variables, including baseline %HbF, whereas MTD was best predicted by 5 variables, including serum creatinine. Pharmacogenetics analysis showed single nucleotide polymorphisms influencing baseline %HbF, including 5 within BCL11A, but none influencing MTD %HbF or dose. Accurate prediction of hydroxyurea treatment responses for SCA remains a worthy but elusive goal. PMID:21876119

Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes.

PubMed

Pandey, Veena; Ansari, Mohammad W; Tula, Suresh; Yadav, Sandep; Sahoo, Ranjan K; Shukla, Nandini; Bains, Gurdeep; Badal, Shail; Chandra, Subhash; Gaur, A K; Kumar, Atul; Shukla, Alok; Kumar, J; Tuteja, Narendra

2016-05-01

This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th-56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress.

The relationship between total cholinesterase activity and mortality in four butterfly species

USGS Publications Warehouse

Bargar, Timothy A.

2012-01-01

The relationship between total cholinesterase activity (TChE) and mortality in four butterfly species (great southern white [Ascia monuste], common buckeye [Junonia coenia], painted lady [Vanessa cardui], and julia butterflies [Dryas julia]) was investigated. Acute contact toxicity studies were conducted to evaluate the response (median lethal dose [LD50] and TChE) of the four species following exposure to the organophosphate insecticide naled. The LD50 for these butterflies ranged from 2.3 to 7.6 μg/g. The average level of TChE inhibition associated with significant mortality ranged from 26 to 67%, depending on the species. The lower bounds of normal TChE activity (2 standard deviations less than the average TChE for reference butterflies) ranged from 8.4 to 12.3 μM/min/g. As a percentage of the average reference TChE activity for the respective species, the lower bounds were similar to the inhibition levels associated with significant mortality, indicating there was little difference between the dose resulting in significant TChE inhibition and that resulting in mortality.

Evaluation of energy in heated water vapor for the application of lung volume reduction in patients with severe emphysema.

PubMed

Henne, Erik; Kesten, Steven; Herth, Felix J F

2013-01-01

A method of achieving endoscopic lung volume reduction for emphysema has been developed that utilizes precise amounts of thermal energy in the form of water vapor to ablate lung tissue. This study evaluates the energy output and implications of the commercial InterVapor system and compares it to the clinical trial system. Two methods of evaluating the energy output of the vapor systems were used, a direct energy measurement and a quantification of resultant thermal profile in a lung model. Direct measurement of total energy and the component attributable to gas (vapor energy) was performed by condensing vapor in a water bath and measuring the temperature and mass changes. Infrared images of a lung model were taken after vapor delivery. The images were quantified to characterize the thermal profile. The total energy and vapor energy of the InterVapor system was measured at various dose levels and compared to the clinical trial system at a dose of 10.0 cal/g. An InterVapor dose of 8.5 cal/g was found to have the most similar vapor energy output with the smallest associated reduction in total energy. This was supported by characterization of the thermal profile in the lung model that demonstrated the profile of InterVapor at 8.5 cal/g to not exceed the profile of the clinical trial system. Considering both total energy and vapor energy is important during the development of clinical vapor applications. For InterVapor, a closer study of both energy types justified a reduced target vapor-dosing range for lung volume reduction. The clinical implication is a potential improvement for benefiting the risk profile. Copyright © 2013 S. Karger AG, Basel.

Phase I/II clinical trial of 2-Difluoromethylornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma

PubMed Central

Skorupski, Katherine A.; O'Brien, Thomas G.; Guerrero, Teri; Rodriguez, Carlos O.; Burns, Mark R.

2011-01-01

Polyamines are essential for cell proliferation. Their production is dysregulated in many cancers and polyamine depletion leads to tumor regression in mouse models of SCC. The purpose of this study was to determine the maximally tolerated dose of the polyamine transport inhibitor, MQT 1426, when combined with the ornithine decarboxylase inhibitor, DFMO, and to determine whether this therapy results in reduction in tumor polyamine levels. Thirteen cats with oral SCC received both drugs orally and serial tumor biopsies were obtained for polyamine measurement. Cats were monitored for response to therapy and toxicity. A maximum tolerated dose of MQT 1426 when combined with DFMO was determined. Dose limiting toxicity was vestibular in nature, but was fully reversible. Spermidine and total polyamine levels decreased significantly in tissues, 2 cats experienced objective tumor regression, and 6 cats had stable disease. These results suggest that further study of polyamine depletion therapies is warranted. PMID:22077408

A biosphere modeling methodology for dose assessments of the potential Yucca Mountain deep geological high level radioactive waste repository.

PubMed

Watkins, B M; Smith, G M; Little, R H; Kessler, J

1999-04-01

Recent developments in performance standards for proposed high level radioactive waste disposal at Yucca Mountain suggest that health risk or dose rate limits will likely be part of future standards. Approaches to the development of biosphere modeling and dose assessments for Yucca Mountain have been relatively lacking in previous performance assessments due to the absence of such a requirement. This paper describes a practical methodology used to develop a biosphere model appropriate for calculating doses from use of well water by hypothetical individuals due to discharges of contaminated groundwater into a deep well. The biosphere model methodology, developed in parallel with the BIOMOVS II international study, allows a transparent recording of the decisions at each step, from the specification of the biosphere assessment context through to model development and analysis of results. A list of features, events, and processes relevant to Yucca Mountain was recorded and an interaction matrix developed to help identify relationships between them. Special consideration was given to critical/potential exposure group issues and approaches. The conceptual model of the biosphere system was then developed, based on the interaction matrix, to show how radionuclides migrate and accumulate in the biosphere media and result in potential exposure pathways. A mathematical dose assessment model was specified using the flexible AMBER software application, which allows users to construct their own compartment models. The starting point for the biosphere calculations was a unit flux of each radionuclide from the groundwater in the geosphere into the drinking water in the well. For each of the 26 radionuclides considered, the most significant exposure pathways for hypothetical individuals were identified. For 14 of the radionuclides, the primary exposure pathways were identified as consumption of various crops and animal products following assumed agricultural use of the contaminated water derived from the deep well. Inhalation of dust (11 radionuclides) and external irradiation (1 radionuclide) were also identified as significant exposure modes. Contribution to the total flux to dose conversion factor from the drinking water pathway for each radionuclide was also assessed and for most radionuclides was found to be less than 10% of the total flux to dose conversion factor summed across all pathways. Some of the uncertainties related to the results were considered. The biosphere modeling results have been applied within an EPRI Total Systems Performance Assessment of Yucca Mountain. Conclusions and recommendations for future performance assessments are provided.

LDEF: Dosimetric measurement results (AO 138-7 experiment)

NASA Technical Reports Server (NTRS)

Bourrieau, J.

1993-01-01

One of the objectives of the AO 138-7 experiment on board the Long Duration Exposure Facility (LDEF) was a total dose measurement with Thermo Luminescent Detectors (TLD 100). Two identical packages, both of them including five TLD's inside various aluminum shields, are exposed to the space environment in order to obtain the absorbed dose profile. Radiation fluence received during the total mission length was computed, taking into account the trapped particles (AE8 and AP8 models during solar maximum and minimum periods) and the cosmic rays; due to the magnetospheric shielding the solar proton fluences are negligible on the LDEF orbit. The total dose induced by these radiations inside a semi infinite plane shield of aluminum are computed with the radiation transport codes available at DERTS. The dose profile obtained is in good agreement with the evaluation by E.V. Benton. TLD readings are performed after flight; due to the mission duration increase a post flight calibration was necessary in order to cover the range of the in flight induced dose. The results obtained, similar (plus or minus 30 percent) for both packages, are compared with the dose profile computation. For thick shields it seems that the measurements exceed the forecast (about 40 percent). That can be due to a cosmic ray and trapped proton contributions coming from the backside (assumed as perfectly shielded by the LDEF structure in the computation), or to an underestimate of the proton or cosmic ray fluences. A fine structural shielding analysis should be necessary in order to determine the origin of this slight discrepancy between forecast and in flight measurements. For the less shielded dosimeters, mainly exposed to the trapped electron flux, a slight overestimation of the dose (less than 40 percent) appears. Due to the dispersion of the TLD's response, this cannot be confirmed. In practice these results obtained on board LDEF, with less than a factor 1.4 between measurements and forecast, reinforce the validity of the computation methods and models used for the long term evaluation of the radiation levels (flux and dose) encountered in space on low inclination and altitude Earth orbits.

LDEF: Dosimetric measurement results (AO 138-7 experiment)

NASA Astrophysics Data System (ADS)

Bourrieau, J.

1993-04-01

One of the objectives of the AO 138-7 experiment on board the Long Duration Exposure Facility (LDEF) was a total dose measurement with Thermo Luminescent Detectors (TLD 100). Two identical packages, both of them including five TLD's inside various aluminum shields, are exposed to the space environment in order to obtain the absorbed dose profile. Radiation fluence received during the total mission length was computed, taking into account the trapped particles (AE8 and AP8 models during solar maximum and minimum periods) and the cosmic rays; due to the magnetospheric shielding the solar proton fluences are negligible on the LDEF orbit. The total dose induced by these radiations inside a semi infinite plane shield of aluminum are computed with the radiation transport codes available at DERTS. The dose profile obtained is in good agreement with the evaluation by E.V. Benton. TLD readings are performed after flight; due to the mission duration increase a post flight calibration was necessary in order to cover the range of the in flight induced dose. The results obtained, similar (plus or minus 30 percent) for both packages, are compared with the dose profile computation. For thick shields it seems that the measurements exceed the forecast (about 40 percent). That can be due to a cosmic ray and trapped proton contributions coming from the backside (assumed as perfectly shielded by the LDEF structure in the computation), or to an underestimate of the proton or cosmic ray fluences. A fine structural shielding analysis should be necessary in order to determine the origin of this slight discrepancy between forecast and in flight measurements. For the less shielded dosimeters, mainly exposed to the trapped electron flux, a slight overestimation of the dose (less than 40 percent) appears. Due to the dispersion of the TLD's response, this cannot be confirmed. In practice these results obtained on board LDEF, with less than a factor 1.4 between measurements and forecast, reinforce the validity of the computation methods and models used for the long term evaluation of the radiation levels (flux and dose) encountered in space on low inclination and altitude Earth orbits.

Total marrow irradiation using Helical TomoTherapy

NASA Astrophysics Data System (ADS)

Garcia-Fernandez, Lourdes Maria

Clinical dose response data of human tumours are limited or restricted to a radiation dose range determined by the level of toxicity to the normal tissues. This is the case for the most common disseminated plasma cell neoplasm, multiple myeloma, where the maximum dose deliverable to the entire bony skeleton using a standard total body irradiation (TBI) technique is limited to about 12 Gy. This study is part of scientific background of a phase I/II dose escalation clinical trial for multiple myeloma using image-guided intensity modulated radiotherapy (IG-IMRT) to deliver high dose to the entire volume of bone marrow with Helical TomoTherapy (HT). This relatively new technology can deliver highly conformal dose distributions to complex target shapes while reducing the dose to critical normal tissues. In this study tools for comparing and predicting the effectiveness of different approaches to total marrow irradiation (TMI) using HT were provided. The expected dose response for plasma cell neoplasms was computed and a radiobiological evaluation of different treatment cohorts in a dose escalating study was performed. Normal tissue complication probability (NTCP) and tumour control probability (TCP) models were applied to an actual TMI treatment plan for a patient and the implications of using different longitudinal field widths were assessed. The optimum dose was ˜39 Gy for which a predicted tumour control of 95% (+/-3%) was obtained, with a predicted 3% (0, 8%) occurrence of radiation pneumonitis. Tissue sparing was seen by using smaller field widths only in the organs of the head. This suggests it would be beneficial to use the small fields in the head only since using small fields for the whole treatment would lead to long treatment times. In TMI it may be necessary to junction two longitudinally adjacent treatment volumes to form a contiguous planning target volume PTV. For instance, this is the case when a different SUP-INF spatial resolution is required or when the PTV length exceeds the bed travel distance. In this work, the dosimetric challenges associated with junctioning longitudinally adjacent PTVs with HT were analyzed and the feasibility of PTV junctioning was demonstrated. The benefits of spatially dividing or splitting the treatment into a few sub-treatments along the longitudinal direction were also investigated.

Effect of γ-irradiation on bioactivity, fatty acid compositions and volatile compounds of clary sage seed (Salvia sclarea L.).

PubMed

Yalcin, Hasan; Ozturk, Ismet; Tulukcu, Eray; Sagdic, Osman

2011-09-01

Clary sage seeds (Salvia sclarea L.) were obtained from plants cultivated, and 2.5, 4.0, 5.5, and 7.0 kGy doses of γ-irradiation were applied to the clary sage seeds. They were then analyzed for their protein, ash, oil and dry matter contents, and fatty acid composition. Additionally, the total phenolic contents, antiradical, antioxidant activities, and volatile compounds of the clary sage seed extract were determined. There was no significant difference in protein content. However, the moisture, oil, and ash contents of the samples were affected by irradiation. While the 7 kGy dose had a positive effect on the total phenolic content and antiradical activity of the sage seed extract, all doses have negative effects on the antioxidant activity of the sage seed. The main fatty acid of the sage seed was remarkably found as α-linolenic acid. The four irradiation levels caused significant differences in fatty acid composition by affecting all fatty acids except palmitic, palmitoleic, and eicosenoic acids. The dominant volatile compounds of control sage seed were found as β-pinene (18.81%) and limonene (15.60%). Higher doses of the irradiation decreased volatile components of sage seed. Clary sage seed including high omega-3 can be irradiated with low doses (≤ 2.5 kGy) of γ-irradiation. Clary sage is one of the most popular Salvia species in Turkey and many countries. Clary sage seed has approximately 29% oil content and this oil contains >50% of α-linolenic acid. γ-Irradiation is widely applied in the preservation of spice quality. The present study shows that the antioxidant activity of the clary sage seed is decreased by γ-irradiation. Additionally, higher doses of irradiation also decreased the volatile components of sage seed. Therefore, we suggest that clary sage seed which includes high levels of omega-3 should be irradiated with low doses (≤ 2.5 kGy) of γ-irradiation. © 2011 Institute of Food Technologists®

Alterations in carbohydrates and the protein metabolism of the harmful freshwater vector snail Lymnaea acuminata induced by the Euphorbia tirucalli latex extract.

PubMed

Tiwari, Sudhanshu; Singh, A

2005-11-01

To know the short- as well as long-term effect of aqueous latex extracts of Euphorbia tirucalli on carbohydrate and protein metabolism, the snail Lymnaea acuminata was exposed to sublethal doses of 0.37 and 0.55 mg/L for a 24-h and 0.20 and 0.31 mg/L for a 96-h exposure period. Significant (P<0.05) alterations in the glycogen, pyruvate, lactate, total protein, and free amino acid level, as well as in the activity of enzyme lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, protease, aspartate aminotransaminase, and alanine aminotransaminase were observed in the nervous, hepatopancreatic, and ovotestis tissues of the freshwater vector snail L. acuminata exposed to sublethal doses of E. tirucalli latex extract. The alterations in all biochemical parameters were significantly (P<0.05) time and dose dependent. After the 7th day of the withdrawal of treatment, there was significant (P<0.05) recovery in glycogen, pyruvate, lactate, total protein, and the free amino acid level and in the activity of the lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, protease, aspartate aminotransaminase and alanine aminotransaminase enzymes in all three of the studied tissues of the snail, which supports the view that the plant product is safe for use as a molluscicide for the control of harmful freshwater vector snails in the aquatic environment.

Chromium-induced membrane damage: protective role of ascorbic acid.

PubMed

Dey, S K; Nayak, P; Roy, S

2001-07-01

Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80-100 g body weight). It has been observed that the intoxication with chromium (i.p.) at the dose of 0.8 mg/100 g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospholipid of both liver and kidney. The alkaline phosphatase, total ATPase and Na(+)-K(+)-ATPase activities were significantly decreased in both liver and kidney after chromium treatment, except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid (i.p. at the dose of 0.5 mg/100 g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

Long-term treatment of onchocerciasis patients from the Liberian rain-forest with low doses of diethylcarbamazine citrate after complete nodulectomy.

PubMed

Albiez, E J

1983-12-01

60 completely nodulectomized volunteers from the Liberian rain-forest were given an initial treatment with diethylcarbamazine citrate (DEC-C) for one week with gradually increasing doses up to a total of 1.1 g per patient. A long-term treatment followed with 50 mg DEC-C per week for 12 months. Immediately after the initial treatment the mean microfilarial density decreased to 4% to 6% of the pre-treatment level. After one year the microfilarial density had again increased to 12% to 29% of the pre-treatment level. Although the intake of the weekly 50 mg DEC-C was in no case regular, the microfilarial densities could be kept at a low level throughout the trial. However, even with the combined treatment--preceding nodulectomy and long-term trial with DEC-C--it was not possible to get the patients free from microfilariae.

Evaluation of the peripheral dose to uterus in breast carcinoma radiotherapy.

PubMed

Martín Rincón, C; Jerez Sainz, I; Modolell Farré, I; España López, M L; López Franco, P; Muñiz, J L; Romero, A M; Rodríguez, R

2002-01-01

The absorbed dose outside of the direct fields of radiotherapy treatment (or peripheral dose, PD) is responsible for radiation exposure of the fetus in pregnant women. Because the radiological protection of the unborn child is of particular concern in the early period of the pregnancy, the aim of this study is to estimate the PD in order to assess the absorbed dose in the uterus in a pregnant patient irradiated for breast carcinoma therapy. The treatment was simulated on an Alderson-Rando anthropomorphic phantom, and the radiation dose to the fetus was measured using an ionisation chamber and thermoluminescence dosemeters. Two similar treatments plans with and without wedges were delivered, using a 6 MV photon beam with two isocentric opposite tangential fields with a total dose of 50 Gy, in accordance with common established procedures. Average field parameters for more than 300 patients were studied. Measurements showed the fetal dose to be slightly lower than 50 mGy, a level at which the risk to the fetus is uncertain, although several authors consider this value as the dose threshold for deterministic effects. The planning system (PS) underestimated PD values and no significant influence was found with the use of wedge filters.

Type 2 Diabetic Rats on Diet Supplemented With Chromium Malate Show Improved Glycometabolism, Glycometabolism-Related Enzyme Levels and Lipid Metabolism

PubMed Central

Feng, Weiwei; Zhao, Ting; Mao, Guanghua; Wang, Wei; Feng, Yun; Li, Fang; Zheng, Daheng; Wu, Huiyu; Jin, Dun; Yang, Liuqing; Wu, Xiangyang

2015-01-01

Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed that fasting blood glucose, serum insulin level, insulin resistance index and C-peptide level in the high dose group had a significant downward trend when compared with the model group, chromium picolinate group and chromium trichloride group. The hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, Glut4, phosphor-AMPKβ1 and Akt levels in the high dose group were significantly higher than those of the model, chromium picolinate and chromium trichloride groups. Chromium malate in a high dose group can significantly increase high density lipoprotein cholesterol level while decreasing the total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared with chromium picolinate and chromium trichloride. The serum chromium content in chromium malate and chromium picolinate group is significantly higher than that of the chromium trichloride group. The results indicated that the curative effects of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism changes are better than those of chromium picolinate and chromium trichloride. Chromium malate contributes to glucose uptake and transport in order to improved glycometabolism and glycometabolism-related enzymes. PMID:25942313

Type 2 diabetic rats on diet supplemented with chromium malate show improved glycometabolism, glycometabolism-related enzyme levels and lipid metabolism.

PubMed

Feng, Weiwei; Zhao, Ting; Mao, Guanghua; Wang, Wei; Feng, Yun; Li, Fang; Zheng, Daheng; Wu, Huiyu; Jin, Dun; Yang, Liuqing; Wu, Xiangyang

2015-01-01

Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed that fasting blood glucose, serum insulin level, insulin resistance index and C-peptide level in the high dose group had a significant downward trend when compared with the model group, chromium picolinate group and chromium trichloride group. The hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, Glut4, phosphor-AMPKβ1 and Akt levels in the high dose group were significantly higher than those of the model, chromium picolinate and chromium trichloride groups. Chromium malate in a high dose group can significantly increase high density lipoprotein cholesterol level while decreasing the total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared with chromium picolinate and chromium trichloride. The serum chromium content in chromium malate and chromium picolinate group is significantly higher than that of the chromium trichloride group. The results indicated that the curative effects of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism changes are better than those of chromium picolinate and chromium trichloride. Chromium malate contributes to glucose uptake and transport in order to improved glycometabolism and glycometabolism-related enzymes.

Radiometric and Radiation Response of Visible FPAs

NASA Technical Reports Server (NTRS)

Hubbs, John

2007-01-01

The readout integrated circuit (ROIC) used in these devices was originally developed for use in space based infrared systems operating at deep cryogenic temperatures and was selected because of its proven tolerance to total ionizing radiation? The detectors are a 128 x 128 array of 60 pm x 60 pm pixel elements that have been anti-reflection (AR) coated to improve the response at very short wavelengths. These visible focal plane arrays were operated at -40 C (233 K). Two focal planes were characterized using cobalt-60 radiation to produce ionizing total dose damage in the VFPAs. Both operational and performance data were obtained as functions of total dose. The first device tested showed no appreciable change in responsivity or noise up to 300 krad(Si). However, at the next dose level of 600 krad(Si), the readout was non-operational due to failure in the digital circuitry. The second device was characterized to a total dose of 750 krad(Si) with no observed change in responsivity. An increase dark current was observed in both devices, and in the second device, the dark current caused an increase in noise at low irradiance at 400 krad(Si) and above. The increase in dark current was somewhat un-expected for visible PIN detectors. The median dark current increased more than two orders of magnitude at 300 krad(Si) for the first device and a factor of 350 at 750 krad(Si) for pixels near the edge for the second device. The dark current was found to be a strong function of detector bias, with pixels near the edge of the array showing a greater increase in dark current with bias than those near the center. Since the optical response was not a function of bias, it is hypothesized that the dark current is a surface effect and that the variation in dark current with location is due to a variation in pixel bias, caused by a voltage drop across the pixel common lead. As the total dose increased, the dark current and the voltage drop increased

Radiation-Induced Liver Injury in Three-Dimensional Conformal Radiation Therapy (3D-CRT) for Postoperative or Locoregional Recurrent Gastric Cancer: Risk Factors and Dose Limitations.

PubMed

Li, Guichao; Wang, Jiazhou; Hu, Weigang; Zhang, Zhen

2015-01-01

This study examined the status of radiation-induced liver injury in adjuvant or palliative gastric cancer radiation therapy (RT), identified risk factors of radiation-induced liver injury in gastric cancer RT, analysed the dose-volume effects of liver injury, and developed a liver dose limitation reference for gastric cancer RT. Data for 56 post-operative gastric cancer patients and 6 locoregional recurrent gastric cancer patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed. Forty patients (65%) were administered concurrent chemotherapy. Pre- and post-radiation chemotherapy were given to 61 patients and 43 patients, respectively. The radiation dose was 45-50.4 Gy in 25-28 fractions. Clinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were included in the analysis. Univariate analyses with a non-parametric rank test (Mann-Whitney test) and logistic regression test and a multivariate analysis using a logistic regression test were completed. We also analysed the correlation between RT and the changes in serum chemistry parameters [including total bilirubin, (TB), direct bilirubin (D-TB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum albumin (ALB)] after RT. The Child-Pugh grade progressed from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of classic radiation-induced liver disease (RILD) were observed, and 2 patients had both Child-Pugh grade progression and classic RILD. No cases of non-classic radiation liver injury occurred in the study population. Among the tested clinical parameters, the total number of chemotherapy cycles correlated with liver function injury. V35 and ALP levels were significant predictive factors for radiation liver injury. In 3D-CRT for gastric cancer patients, radiation-induced liver injury may occur and affect the overall treatment plan. The total number of chemotherapy cycles correlated with liver function injury, and V35 and ALP are significant predictive factors for radiation-induced liver injury. Our dose limitation reference for liver protection is feasible.

Effects of aeration on water quality from septic system leachfields.

PubMed

Potts, David A; Görres, Josef H; Nicosia, Erika L; Amador, José A

2004-01-01

We conducted a pilot-scale study at a research facility in southeastern Connecticut to assess the effects of leachfield aeration on removal of nutrients and pathogens from septic system effluent. Treatments consisted of lysimeters periodically aerated to maintain a headspace O(2) concentration of 0.209 mol mol(-1) (AIR) or vented to an adjacent leachfield trench (LEACH) and were replicated three times. All lysimeters were dosed with effluent from a septic tank for 24 mo at a rate of 12 cm d(-1) and subsequently for 2 mo at 4 cm d(-1). LEACH lysimeters had developed a clogging mat, or biomat, 20 mo before the beginning of our study. The level of aeration in the AIR treatment was held constant regardless of loading rate. No conventional biomat developed in the AIR treatment, whereas a biomat was present in the LEACH lysimeters. The headspace of LEACH lysimeters was considerably depleted in O(2) and enriched in CH(4), CO(2), and H(2)S relative to AIR lysimeters. Drainage water from AIR lysimeters was saturated with O(2) and had significantly lower pH, five-day biological oxygen demand (BOD(5)), and ammonium, and higher levels of nitrate and sulfate than LEACH lysimeters regardless of dosing rate. By contrast, significantly lower levels of total N and fecal coliform bacteria were observed in AIR than in LEACH lysimeters only at the higher dosing rate. No significant differences in total P removal were observed. Our results suggest that aeration may improve the removal of nitrogen, BOD(5), and fecal coliforms in leachfield soil, even in the absence of a biomat.

Dose-response association of moderate-to-vigorous physical activity with cardiovascular biomarkers and all-cause mortality: Considerations by individual sports, exercise and recreational physical activities.

PubMed

Loprinzi, Paul D

2015-12-01

Previous research demonstrates that moderate-to-vigorous physical activity (MVPA) is associated with reduced all-cause mortality risk. Our understanding of whether individual physical activities are associated with all-cause mortality is less understood. Data from the 1999-2006 NHANES were employed, with follow-up through 2011. 48 different individual physical activities (e.g., swimming, running, bicycling) were assessed, and total MVPA MET-min-month was calculated based on their responses to these 48 individual physical activities. Greater engagement in MVPA was associated with more favorable cardiovascular biomarkers, particularly for men. Even after adjustment for total MVPA, different individual physical activities were associated with cardiovascular biomarkers across gender. When compared to those not meeting guidelines (0-1999 MVPA MET-min-month), a dose-response association between MVPA and mortality was observed, with those engaging in 5 times the guideline level having the lowest risk of all-cause mortality (45% reduced risk). There was no evidence of a harmful effect of very high MVPA (e.g., 20,000+ MVPA MET-min-month). Engaging in MVPA even below the minimum recommendation was associated with survival benefits, and the greatest survival effects occurred at a dose of approximately 5 times the minimum recommendation. Although very high levels (e.g., 10 times the minimum recommendation) of self-reported MVPA did not demonstrate the greatest survival effects, high levels of physical activity did not appear to have harmful effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of n-3 polyunsaturated fatty acids and vitamin E on colonic mucosal leukotriene generation, lipid peroxidation, and microcirculation in rats with experimental colitis.

PubMed

Shimizu, T; Igarashi, J; Ohtuka, Y; Oguchi, S; Kaneko, K; Yamashiro, Y

2001-01-01

We investigated the effect of n-3 polyunsaturated fatty acids (PUFAs) on mucosal levels of leukotrienes (LTs) and lipid peroxide (LPO), and on mucosal microcirculation, in rats with experimental colitis induced by dextran sulfate sodium (DSS). We fed Wistar rats a perilla oil-enriched diet containing alpha-linolenic acid (63.2% of total fatty acids) with various doses of vitamin E for 4 weeks, with 4% DSS added to the drinking water during the last week. Control rats were fed a diet produced from soybean oil containing alpha-linolenic acid (5.1% of total fatty acids). Colonic mucosal blood flow was measured with a laser Doppler flowmeter. The mucosal level of arachidonic acid was significantly lower and that of eicosapentaenoic acid was significantly higher in the experimental group. The mucosal level of LPO in the experimental group fed a trace or ordinary dose of vitamin E was significantly higher than that of the controls. The production of LTB(4) and LTC(4) from the colonic mucosa in the experimental group was significantly lower than that in controls. However, only the experimental group fed a vitamin E dose 4-fold higher than that given to the controls showed a significant increase in mucosal blood flow. These results suggest that n-3 PUFAs increase mucosal blood flow by inhibiting LT production when there is sufficient vitamin E to inhibit lipid peroxidation in rats with experimental colitis. Copyright 2001 S. Karger AG, Basel

Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: a phase I clinical study.

PubMed

Schulz, Craig A; Mehta, Minesh P; Badie, Benham; McGinn, Cornelius J; Robins, H Ian; Hayes, Lori; Chappell, Rick; Volkman, Jen; Binger, Kim; Arzoomanian, Rhoda; Simon, Kris; Alberti, Dona; Feierabend, Christine; Tutsch, Kendra D; Kunugi, Keith A; Wilding, George; Kinsella, Timothy J

2004-07-15

To investigate the maximal tolerated dose of a continuous 28-day iododeoxyuridine (IUdr) infusion combined with hyperfractionated accelerated radiotherapy (HART); to analyze the percentage of IUdr-thymidine replacement in peripheral granulocytes as a surrogate marker for IUdr incorporation into tumor cells; to measure the steady-state serum IUdr levels; and to assess the feasibility of continuous IUdr infusion and HART in the management of malignant glioma. Patients were required to have biopsy-proven malignant glioma. Patients received 100 (n = 4), 200 (n = 3), 300 (n = 3), 400 (n = 6), 500 (n = 4), 625 (n = 5), or 781 (n = 6) mg/m(2)/d of IUdr by continuous infusion for 28 days. HART was started 7 days after IUdr initiation. The total dose was 70 Gy (1.2 Gy b.i.d. for 25 days with a 10-Gy boost [2.0 Gy for 5 Saturdays]). Weekly assays were performed to determine the percentage of IUdr-DNA replacement in granulocytes and serum IUdr levels using standard high performance liquid chromatography methods. Standard Phase I toxicity methods were used. Between June 1994 and August 1999, 31 patients were enrolled. No patient had Grade 3 or worse HART toxicity. Grade 3 or greater IUdr toxicity predominantly included neutropenia (n = 3), thrombocytopenia (n = 3), and elevated liver function studies (n = 3). The maximal tolerated dose was 625 mg/m(2)/d. Thymidine replacement in the peripheral granulocytes peaked at 3 weeks and increased with the dose (maximal thymidine replacement 4.9%). The steady-state plasma IUdr level increased with the dose (maximum, 1.5 microM). In our study, continuous long-term IUdr i.v. infusion had a maximal tolerated dose of 625 mg/m(2)/d. Granulocyte incorporation data verified the concept that prolonged IUdr infusion results in IUdr-DNA replacement that corresponds to a high degree of cell labeling. IUdr steady-state plasma levels increased with increasing dose and attained levels needed for clinical radiosensitization. Continuous IUdr infusion and HART were both feasible and well tolerated.

Development and Validation of a Novel Vancomycin Dosing Nomogram for Achieving High-Target Trough Levels at 2 Canadian Teaching Hospitals

PubMed Central

Thalakada, Rosanne; Legal, Michael; Lau, Tim T Y; Luey, Tiffany; Batterink, Josh; Ensom, Mary H H

2012-01-01

Background: Recent guidelines recommend a vancomycin trough (predose) level between 15 and 20 mg/L in the treatment of invasive gram-positive infections, but most initial dosing nomograms are designed to achieve lower targets (5–15 mg/L). Clinicians need guidance about appropriate initial dosing to achieve the higher target. Objective: To develop and validate a high-target vancomycin dosing nomogram to achieve trough levels of 15–20 mg/L. Methods: A retrospective study was conducted at 2 teaching hospitals, St Paul’s Hospital and Vancouver General Hospital in Vancouver, British Columbia. Patients who were treated with vancomycin between January 2008 and June 2010 and who had achieved a trough level of 14.5–20.5 mg/L were identified. Demographic and clinical data were collected. Multiple linear regression was used to develop a vancomycin dosing nomogram for each hospital site. An integrated nomogram was constructed by merging the data from the 2 hospitals. A unique set of patients at each institution was used for validating their respective nomograms and a pooled group of patients for validating the integrated nomogram. Predictive success was evaluated, and a nomogram was deemed significantly different from another nomogram if p < 0.05 via “χ2 testing. Results: Data from 78 patients at one hospital and 91 patients at the other were used in developing the respective institutional nomograms. For each hospital’s data set, both age and initial serum creatinine were significantly associated with the predicted dosing interval (p < 0.001). Validation in a total of 105 test patients showed that the integrated nomogram had a predictive success rate of 56%. Conclusions: A novel vancomycin dosing nomogram was developed and validated at 2 Canadian teaching hospitals. This integrated nomogram is a tool that clinicians can use in selecting appropriate initial vancomycin regimens on the basis of age and serum creatinine, to achieve high-target levels of 15–20 mg/L. The nomogram should not replace clinical judgment for patients with unstable and/or reduced renal function. PMID:22783028

Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial.

PubMed

Bakris, George L; Pitt, Bertram; Weir, Matthew R; Freeman, Mason W; Mayo, Martha R; Garza, Dahlia; Stasiv, Yuri; Zawadzki, Rezi; Berman, Lance; Bushinsky, David A

2015-07-14

Hyperkalemia is a potentially life-threatening condition predominantly seen in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who may also have diabetes, heart failure, or both. To select starting doses for a phase 3 study and to evaluate the long-term safety and efficacy of a potassium-binding polymer, patiromer, in outpatients with hyperkalemia. Phase 2, multicenter, open-label, dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in Europe from June 2011 to June 2013 evaluating patiromer in 306 outpatients with type 2 diabetes (estimated glomerular filtration rate, 15 to <60 mL/min/1.73 m2 and serum potassium level >5.0 mEq/L). All patients received RAAS inhibitors prior to and during study treatment. Patients were stratified by baseline serum potassium level into mild or moderate hyperkalemia groups and received 1 of 3 randomized starting doses of patiromer (4.2 g [n = 74], 8.4 g [n = 74], or 12.6 g [n = 74] twice daily [mild hyperkalemia] or 8.4 g [n = 26], 12.6 g [n = 28], or 16.8 g [n = 30] twice daily [moderate hyperkalemia]). Patiromer was titrated to achieve and maintain serum potassium level 5.0 mEq/L or lower. The primary efficacy end point was mean change in serum potassium level from baseline to week 4 or prior to initiation of dose titration. The primary safety end point was adverse events through 52 weeks. Secondary efficacy end points included mean change in serum potassium level through 52 weeks. A total of 306 patients were randomized. The least squares mean reduction from baseline in serum potassium level at week 4 or time of first dose titration in patients with mild hyperkalemia was 0.35 (95% CI, 0.22-0.48) mEq/L for the 4.2 g twice daily starting-dose group, 0.51 (95% CI, 0.38-0.64) mEq/L for the 8.4 g twice daily starting-dose group, and 0.55 (95% CI, 0.42-0.68) mEq/L for the 12.6 g twice daily starting-dose group. In those with moderate hyperkalemia, the reduction was 0.87 (95% CI, 0.60-1.14) mEq/L for the 8.4 g twice daily starting-dose group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 12.6 g twice daily starting-dose group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 16.8 g twice daily starting-dose group (P < .001 for all changes vs baseline by hyperkalemia starting-dose groups within strata). From week 4 through week 52, statistically significant mean decreases in serum potassium levels were observed at each monthly point in patients with mild and moderate hyperkalemia. Over the 52 weeks, hypomagnesemia (7.2%) was the most common treatment-related adverse event, mild to moderate constipation (6.3%) was the most common gastrointestinal adverse event, and hypokalemia (<3.5 mEq/L) occurred in 5.6% of patients. Among patients with hyperkalemia and diabetic kidney disease, patiromer starting doses of 4.2 to 16.8 g twice daily resulted in statistically significant decreases in serum potassium level after 4 weeks of treatment, lasting through 52 weeks. clinicaltrials.gov Identifier:NCT01371747.

Simultaneous removal of colour, phosphorus and disinfection from treated wastewater using an agent synthesized from amorphous silica and hydrated lime.

PubMed

Yamashita, Takahiro; Aketo, Tsuyoshi; Minowa, Nobutaka; Sugimoto, Kiyomi; Yokoyama, Hiroshi; Ogino, Akifumi; Tanaka, Yasuo

2013-01-01

An agent synthesized from amorphous silica and hydrated lime (CSH-lime) was investigated for its ability to simultaneously remove the colour, phosphorus and disinfection from the effluents from wastewater treatment plants on swine farms. CSH-lime removed the colour and phosphate from the effluents, with the colour-removal effects especially high at pH 12, and phosphorous removal was more effective in strongly alkaline conditions (pH > 10). Colour decreased from 432 +/-111 (mean +/- SD) to 107 +/- 41 colour units and PO4(3-)P was reduced from 45 +/- 39 mg/L to undetectable levels at the CSH-lime dose of 2.0% w/v. Moreover, CSH-lime reduced the total organic carbon from 99.0 to 37.9 mg/L at the dose of 2.0% w/v and was effective at inactivating total heterotrophic and coliform bacteria. However, CSH-lime did not remove nitrogen compounds such as nitrite, nitrate and ammonium. Colour was also removed from dye solutions by CSH-lime, at the same dose.

Population Pharmacokinetic/Pharmacodynamic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using an Indirect Response Model to Predict Low-Density Lipoprotein Cholesterol Lowering: Support for a Biologics License Application Submission: Part II.

PubMed

Nicolas, Xavier; Djebli, Nassim; Rauch, Clémence; Brunet, Aurélie; Hurbin, Fabrice; Martinez, Jean-Marie; Fabre, David

2018-05-03

Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels. This analysis aimed to develop and qualify a population pharmacokinetic/pharmacodynamic model for alirocumab based on pooled data obtained from 13 phase I/II/III clinical trials. From a dataset of 2799 individuals (14,346 low-density lipoprotein-cholesterol values), individual pharmacokinetic parameters from the population pharmacokinetic model presented in Part I of this series were used to estimate alirocumab concentrations. As a second step, we then developed the current population pharmacokinetic/pharmacodynamic model using an indirect response model with a Hill coefficient, parameterized with increasing low-density lipoprotein cholesterol elimination, to relate alirocumab concentrations to low-density lipoprotein cholesterol values. The population pharmacokinetic/pharmacodynamic model allowed the characterization of the pharmacokinetic/pharmacodynamic properties of alirocumab in the target population and estimation of individual low-density lipoprotein cholesterol levels and derived pharmacodynamic parameters (the maximum decrease in low-density lipoprotein cholesterol values from baseline and the difference between baseline low-density lipoprotein cholesterol and the pre-dose value before the next alirocumab dose). Significant parameter-covariate relationships were retained in the model, with a total of ten covariates (sex, age, weight, free baseline PCSK9, total time-varying PCSK9, concomitant statin administration, total baseline PCSK9, co-administration of high-dose statins, disease status) included in the final population pharmacokinetic/pharmacodynamic model to explain between-subject variability. Nevertheless, the high number of covariates included in the model did not have a clinically meaningful impact on model-derived pharmacodynamic parameters. This model successfully allowed the characterization of the population pharmacokinetic/pharmacodynamic properties of alirocumab in its target population and the estimation of individual low-density lipoprotein cholesterol levels.

[Estimation of Maximum Entrance Skin Dose during Cerebral Angiography].

PubMed

Kawauchi, Satoru; Moritake, Takashi; Hayakawa, Mikito; Hamada, Yusuke; Sakuma, Hideyuki; Yoda, Shogo; Satoh, Masayuki; Sun, Lue; Koguchi, Yasuhiro; Akahane, Keiichi; Chida, Koichi; Matsumaru, Yuji

2015-09-01

Using radio-photoluminescence glass dosimeter, we measured the entrance skin dose (ESD) in 46 cases and analyzed the correlations between maximum ESD and angiographic parameters [total fluoroscopic time (TFT); number of digital subtraction angiography (DSA) frames, air kerma at the interventional reference point (AK), and dose-area product (DAP)] to estimate the maximum ESD in real time. Mean (± standard deviation) maximum ESD, dose of the right lens, and dose of the left lens were 431.2 ± 135.8 mGy, 33.6 ± 15.5 mGy, and 58.5 ± 35.0 mGy, respectively. Correlation coefficients (r) between maximum ESD and TFT, number of DSA frames, AK, and DAP were r=0.379 (P<0.01), r=0.702 (P<0.001), r=0.825 (P<0.001), and r=0.709 (P<0.001), respectively. AK was identified as the most useful parameter for real-time prediction of maximum ESD. This study should contribute to the development of new diagnostic reference levels in our country.

Pharmacokinetic and pharmacodynamic modeling to determine the dose of ST-246 to protect against smallpox in humans.

PubMed

Leeds, Janet M; Fenneteau, Frederique; Gosselin, Nathalie H; Mouksassi, Mohamad-Samer; Kassir, Nastya; Marier, J F; Chen, Yali; Grosenbach, Doug; Frimm, Annie E; Honeychurch, Kady M; Chinsangaram, Jarasvech; Tyavanagimatt, Shanthakumar R; Hruby, Dennis E; Jordan, Robert

2013-03-01

Although smallpox has been eradicated, the United States government considers it a "material threat" and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in nonhuman primates (NHPs), together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. The efficacy analysis combined the data from studies conducted at three separate facilities that evaluated treatment following infection with a closely related virus, monkeypox virus (MPXV), in a total of 96 NHPs. The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than 4-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.

Assessment of radiation doses from residential smoke detectors that contain americium-241

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

O'Donnell, F.R.; Etnier, E.L.; Holton, G.A.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq (3 ..mu..Ci) americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv (0.4 prem) to 20 nSv (2 ..mu..rem) for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 ..mu..Svmore » (0.0006 to 8 mrem) to total body and from 0.06 to 800 ..mu..Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft/sup 2/).« less

A comparative analysis of warfarin and low-dose heparin as thromboembolism prophylaxis in total hip replacement patinets.

PubMed Central

Ritter, M A; HamiltonCW

1975-01-01

Warfarin, low-dose heparin, or a combination of low-dose heparin and hydrocortisone was administered to 300 patients undergoing total hip replacement. The lowest incidence of thromboembolic (5 per cent) was attained with Warfarin. Further investigation into the method of administration of low-dose heparin is necessary before it can be used effectively as thromboembolism prophylaxis in total hip replacement patients. The addition of hydrocortisone was not found useful. PMID:1138642