High dose response of as-grown SIMOX substrates

Objective This study aimed to evaluate the dose-response effects of supplemental omega-3 fatty acids on platelet function in healthy volunteers. Methods Twelve healthy volunteers ingested a normal supplemental dose of 1260 mg omega-3 fatty acids daily for 5 days, followed by a high dose of 2520 mg daily for another 5 days. Multiple electrode aggregometry (MEA) with four different agonists was used to measure platelet aggregation before and after the normal- and high-dose regimes. In vitro spiking using physiological doses of omega-3 fatty acids was also performed to determine whether MEA is capable of detecting a platelet-inhibiting effect due to omega-3 fatty acids. Results There were no differences in platelet aggregation measured by the MEA assay in healthy volunteers after intake of either the normal or high dose of omega-3 fatty acids. In the in vitro experiment, a platelet-inhibiting effect of omega-3 fatty acids was shown by an arachidonic acid agonist in MEA . Conclusions Supplemental omega-3 fatty acids do not evoke their positive health effects through inhibition of platelet aggregation measurable with MEA.

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Oral steroid-sparing effect of high-dose inhaled corticosteroids in asthma

European Respiratory Journal ◽

10.1183/13993003.01147-2019 ◽

2019 ◽

Vol 55 (1) ◽

pp. 1901147 ◽

Cited By ~ 7

Author(s):

Ingrid Maijers ◽

Nethmi Kearns ◽

James Harper ◽

Mark Weatherall ◽

Richard Beasley

Keyword(s):

Dose Response ◽

Oral Corticosteroid ◽

Inhaled Corticosteroids ◽

Adrenal Suppression ◽

Oral Steroid ◽

Systemic Effects ◽

High Dose ◽

Response Relationship ◽

Dose Response Relationship ◽

Sparing Effect

BackgroundThe proportion of the efficacy of high-dose inhaled corticosteroids (ICS) in oral corticosteroid-dependent asthma that is due to systemic effects is uncertain. This study aimed to estimate the ICS dose–response relationship for oral corticosteroid-sparing effects in oral corticosteroid-dependent asthma, and to determine the proportion of oral corticosteroid-sparing effects due to their systemic effects, based on the comparative dose–response relationship of ICS versus oral corticosteroids on adrenal suppression.MethodsSystematic review and meta-analysis of randomised controlled trials reporting oral corticosteroid-sparing effects of high-dose ICS in oral corticosteroid-dependent asthma. In addition, reports of oral corticosteroid to ICS dose-equivalence in terms of adrenal suppression were retrieved. The primary outcome was the proportion of the oral corticosteroid-sparing effect of ICS that could be attributed to systemic absorption, per 1000 µg increase of ICS, expressed as a ratio. This ratio estimates the oral corticosteroid sparing effect of ICS due to systemic effects.Results11 studies including 1283 participants reporting oral corticosteroid-sparing effects of ICS were identified. The prednisone dose decrease per 1000 µg increase in ICS varied from 2.1 mg to 4.9 mg, depending on the type of ICS. The ratio of the prednisone-sparing effect due to the systemic effects per 1000 µg of fluticasone propionate was 1.02 (95% CI 0.68–2.08) and for budesonide was 0.93 (95% CI 0.63–1.89).ConclusionIn patients with oral corticosteroid-dependent asthma, the limited available evidence suggests that the majority of the oral corticosteroid-sparing effect of high-dose ICS is likely to be due to systemic effects.

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Dose–Response of TLD-100 in the Dose Range Useful for Hypofractionated Radiotherapy

Dose-Response ◽

10.1177/1559325819894081 ◽

2020 ◽

Vol 18 (1) ◽

pp. 155932581989408 ◽

Cited By ~ 1

Author(s):

Raffaele Liuzzi ◽

Consiglia Piccolo ◽

Vittoria D’Avino ◽

Stefania Clemente ◽

Caterina Oliviero ◽

...

Keyword(s):

Dose Response ◽

Radiation Treatment ◽

Dose Range ◽

Information Criterion ◽

High Dose ◽

Thermoluminescent Dosimeters ◽

Dose Monitoring ◽

Coefficients Of Variation ◽

Best Fitting ◽

Quadratic Models

Purpose: The aim of the study was to exploit the feasibility of thermoluminescent dosimeters (TLDs) in radiation therapy techniques in which high dose per fraction is involved. Methods: Dose–response of TLD-100 (LiF: Mg, Ti) was investigated in both 6-MV photon and 6-MeV electron beams. The element correction factor (ECF) generation method was applied to check the variability of the TLDs response. Two batches of 50 TLDs were divided into groups and exposed in the dose range 0 to 30 Gy. Regression analysis was performed with both linear and quadratic models. For each irradiation beam, the calibration curves were obtained in 3 dose range 0 to 8 Gy, 0 to 10 Gy, and 0 to 30 Gy. The best-fitting model was assessed by the Akaike Information Criterion test. Results: The ECF process resulted a useful tool to reduce the coefficients of variation from original values higher than 5% to about 3.5%, for all the batches exposed. The results confirm the linearity of dose–response curve below the dose level of 10 Gy for photon and electron beam and the supralinear trend above. Conclusion: The TLDs are suitable dosimeters for dose monitoring and verification in radiation treatment involving dose up to 30 Gy in a single fraction.

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The Dose Response for Sprint Interval Training Interventions May Affect the Time Course of Aerobic Training Adaptations

Sports ◽

10.3390/sports7040085 ◽

2019 ◽

Vol 7 (4) ◽

pp. 85

Author(s):

Dominic O’Connor ◽

John K. Malone

Keyword(s):

Dose Response ◽

Time Course ◽

Perceived Exertion ◽

Control Period ◽

Interval Training ◽

High Volume ◽

Peak Oxygen Uptake ◽

Residual Effects ◽

High Dose ◽

Sprint Interval Training

Low vs. high volume sprint-interval training (SIT) sessions have shown similar physiological benefits after 8 weeks. However, the dose response and residual effects of shorter SIT bouts (<10 s) are unknown. Following a 6-wk control period, 13 healthy inactive males were assigned to a low dose (LDG: n = 7) or high dose (HDG: n = 6) supervised 6-wk intervention: ×2/wk of SIT (LDG = 2 sets of 5 × 6 s ON: 18 s OFF bouts; HDG = 4–6 sets); ×1/wk resistance training (3 exercises at 3 × 10 reps). Outcome measures were tested pre and post control (baseline (BL) 1 and 2), 72 h post (0POST), and 3-wk post (3POST) intervention. At 0POST, peak oxygen uptake (VO2peak) increased in the LDG (+16%) and HDG (+11%) vs. BL 2, with no differences between groups (p = 0.381). At 3POST, VO2peak was different between LDG (−11%) and HDG (+3%) vs. 0POST. Positive responses for the intervention’s perceived enjoyment (PE) and rate of perceived exertion (RPE) were found for both groups. Blood pressure, blood lipids, or body composition were not different between groups at any time point. Conclusion: LDG and HDG significantly improved VO2peak at 0POST. However, findings at 3POST suggest compromised VO2peak at 0POST in the HDG due to the delayed time course of adaptations. These findings should be considered when implementing high-dose SIT protocols for non-athletic populations.

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Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice

Journal of Virology ◽

10.1128/jvi.79.1.214-224.2005 ◽

2005 ◽

Vol 79 (1) ◽

pp. 214-224 ◽

Cited By ~ 221

Author(s):

Hiroyuki Nakai ◽

Sally Fuess ◽

Theresa A. Storm ◽

Shin-ichi Muramatsu ◽

Yuko Nara ◽

...

Keyword(s):

Portal Vein ◽

Dose Response ◽

Smooth Muscles ◽

The Body ◽

Specific Gene ◽

High Dose ◽

Adeno Associated Virus ◽

Virus Serotype ◽

High Doses ◽

Dose Response Study

ABSTRACT Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to only a small portion of hepatocytes even after administration of extremely high vector doses. In order to investigate whether rAAV vectors of other serotypes exhibit similar restricted liver transduction, we performed a dose-response study by injecting mice with β-galactosidase-expressing rAAV1 and rAAV8 vectors via the portal vein. The rAAV1 vector showed a blunted dose-response similar to that of rAAV2 at high doses, while the rAAV8 vector dose-response remained unchanged at any dose and ultimately could transduce all the hepatocytes at a dose of 7.2 × 1012 vector genomes/mouse without toxicity. This indicates that all hepatocytes have the ability to process incoming single-stranded vector genomes into duplex DNA. A single tail vein injection of the rAAV8 vector was as efficient as portal vein injection at any dose. In addition, intravascular administration of the rAAV8 vector at a high dose transduced all the skeletal muscles throughout the body, including the diaphragm, the entire cardiac muscle, and substantial numbers of cells in the pancreas, smooth muscles, and brain. Thus, rAAV8 is a robust vector for gene transfer to the liver and provides a promising research tool for delivering genes to various target organs. In addition, the rAAV8 vector may offer a potential therapeutic agent for various diseases affecting nonhepatic tissues, but great caution is required for vector spillover and tight control of tissue-specific gene expression.

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Subchronic Toxicity of Thalidomide in Rodents After 13 Weeks of Oral Administration

International Journal of Toxicology ◽

10.1080/109158199225251 ◽

1999 ◽

Vol 18 (5) ◽

pp. 337-352 ◽

Cited By ~ 9

Author(s):

Steve K. Teo ◽

Nancy J. Trigg ◽

Mary E. Shaw ◽

J. Michael Morgan ◽

Steve D. Thomas

Keyword(s):

Food Consumption ◽

Dose Response ◽

Clinical Chemistry ◽

Female Rats ◽

Male Rats ◽

Lumbar Spinal Cord ◽

High Dose ◽

Significant Finding ◽

Lower Body ◽

Body Weights

The subchronic toxicology of thalidomide was determined in CD-1 mice and F344 rats. Animals (10/sex/dose) were orally dosed at 30,300, and 3000 mg/kg/day over 13 weeks. Control animals were given 1% carboxymethylcellulose. No thalidomide-related mortality occurred throughout the study. Some species and sex differences were seen. In mice, thalidomide had no effect on body weight, food consumption, ophthalmic function or clinical chemistry/hematology, but a dose-dependent orange-pink urine was observed in both sexes. The discoloration was probably due to chromogenic breakdown products of thalidomide. The only significant finding in the mouse study was dose-related hepatic centrilobular hypertrophy in the males. This appeared only at the highest dose in the females. The hypertrophy was correlated with increased liver weight for the high dose of both sexes suggesting enzyme induction. In rats, thalidomide produced lower body weights in both sexes compared to control with a dose-response more evident in males. Male rats dosed at 30, 300, and 3000 mg/kg had body weights that were 8, 11, and 19% below control weight just before necropsy. Corresponding female rats were only 6–7% below control weights at all dose levels. Lower food consumption was observed in male rats and varied between 6–13% below control with no dose-response. Decreased forelimb strength was noted in males and could be due to the lower body weights. Functional observational battery tests and histopathology of the sural nerve and lumbar spinal cord sections suggested that the rat did not develop thalidomide-induced peripheral neuropathy. Mild anemia and leukopenia were seen only in some treated males. A decrease in total and free T4 was more consistent in females. Both sexes had lower thymus weights with no histological correlate compared to control. The no-observed-adverse-effect level for mice and female rats were 3000 mg/kg and 30 mg/kg for male rats.

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