Dose Effect Curve of Somatic Mutations in Ephestia kühniella Z. for Low Dose-range (0–200 r.).

Abstract BACKGROUND Radiosensitivity of glioblastoma (GB) cells of local relapses may be markedly different from the primary tumor. Optimal doses and regimes of re-irradiation GB recurrence is not determined yet. MATERIAL AND METHODS GO1 primary GB cell culture was obtained during removal of a recurrent tumor after combined treatment, including irradiation of the surgical bed. Сell’s culture was irradiated by photon beams with energy 6 MeV and dose rate 600 MU/min. Irradiation performed in 1, 3 and 5 fractions, by 10 different doses for each regime. The dose range was determined experimentally for one fraction (5–250 Gy); for other regimes it was calculated according to the biological equivalent dose conception (3 fractions: 5–450 Gy, 5 fractions: 5–550 Gy). The proliferative activity of cells was investigate by MTT test. The results were normalized to the control. Dose-effect curves were plotted for each irradiation regime.The experimental data were approximated by calculated curves obtained by selecting the optimal parameters of the LQ-model and it’s modification. RESULTS Irradiation of GO1 by 1 fraction with the dose 5–250 Gy, causes a slow decrease in proliferative activity, which reaches a minimum value of 23% at 150 Gy and then remains constant. After irradiation by 3 fractions, proliferative activity of the GO1 gradually decrease only at a total dose over 120 Gy and reaches 37% after 450 Gy. When GO1 was irradiated in 5 fractions, a similar dose-effect curve was obtained, gradual decrease was observed to a value of 52% in the range of 250–500 Gy. Thus, the experimental dose-effect curves for irradiation of recurrence GB cells for 3 and 5 fractions have the appreciable “shoulder”, which could be explained by increased radioresistance. When approximating the experimental data by fitting the parameters of the LQ-model, the use of α/β = 8 provided the slope of the curve, close to the experimental data. For reflecting the “shoulder” an additional summand was introduced into the mathematical expression for the number of proliferating cells - a 105 Gy for 3 fractions and 255 Gy for 5 fractions. CONCLUSION Modified LQ-model could be used for an adequate mathematical description of the effectiveness of fractionated irradiation in relapsed GB culture cells in vitro. It’s necessary to introduce a summand into the formula that determines the formation of a “shoulder” on the dose-effect curve for this. The research was supported financially by RFBR (Project No. 18-29-01061).

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Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02131-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Gertraud Eylert ◽

Reinhard Dolp ◽

Alexandra Parousis ◽

Richard Cheng ◽

Christopher Auger ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Low Dose ◽

Dose Range ◽

High Dose ◽

Full Thickness ◽

Burn Wound ◽

Dermal Regeneration Template ◽

Yorkshire Pigs ◽

Stromal Stem Cells

Abstract Background Multipotent mesenchymal stromal/stem cell (MSC) therapy is under investigation in promising (pre-)clinical trials for wound healing, which is crucial for survival; however, the optimal cell dosage remains unknown. The aim was to investigate the efficacy of different low-to-high MSC dosages incorporated in a biodegradable collagen-based dermal regeneration template (DRT) Integra®. Methods We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,000,000 cells/cm2 of umbilical cord mesenchymal stromal/stem cells on the DRT and grafted it onto full-thickness burn excised wounds. On day 28, comparisons were made between the different low-to-high cell dose groups, the acellular control, a burn wound, and healthy skin. Result We found that the low dose range between 200 and 40,000 cells/cm2 regenerates the full-thickness burn excised wounds most efficaciously, followed by the middle dose range of 200,000–400,000 cells/cm2 and a high dose of 2,000,000 cells/cm2. The low dose of 40,000 cells/cm2 accelerated reepithelialization, reduced scarring, regenerated epidermal thickness superiorly, enhanced neovascularization, reduced fibrosis, and reduced type 1 and type 2 macrophages compared to other cell dosages and the acellular control. Conclusion This regenerative cell therapy study using MSCs shows efficacy toward a low dose, which changes the paradigm that more cells lead to better wound healing outcome.

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Clinically derived dose–effect relationship for hyperthermia given in combination with low-dose radiotherapy

British Journal of Radiology ◽

10.1259/0007-1285-59-697-81 ◽

1986 ◽

Vol 59 (697) ◽

pp. 81-82 ◽

Cited By ~ 2

Author(s):

J. van der Zee ◽

G. C. van Rhoon ◽

J. L. Wike-Hooley ◽

H. S. Reinhold

Keyword(s):

Low Dose ◽

Dose Effect ◽

Effect Relationship ◽

Low Dose Radiotherapy

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Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction

Reproductive Toxicology ◽

10.1016/s0890-6238(02)00006-0 ◽

2002 ◽

Vol 16 (2) ◽

pp. 117-122 ◽

Cited By ~ 211

Author(s):

Shizuka Honma ◽

Atsuko Suzuki ◽

David L. Buchanan ◽

Yoshinao Katsu ◽

Hajime Watanabe ◽

...

Keyword(s):

Bisphenol A ◽

Female Mouse ◽

Low Dose ◽

In Utero ◽

Dose Effect ◽

In Utero Exposure

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CTIM-14. RANDOMIZED PHASE II OPEN LABEL STUDY OF NIVOLUMAB PLUS STANDARD DOSE BEVACIZUMAB VS NIVOLUMAB PLUS LOW DOSE BEVACIZUMAB IN RECURRENT GLIOBLASTOMA (RGBM). NIVOLUMAB BENEFITS OLDER POPULATION

Neuro-Oncology ◽

10.1093/neuonc/noab196.206 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi52-vi52

Author(s):

Manmeet Ahluwalia ◽

David Peereboom ◽

Yasmeen Rauf ◽

Patrick Wen ◽

David Reardon

Keyword(s):

Overall Survival ◽

Low Dose ◽

Standard Dose ◽

Performance Status ◽

Methylation Status ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Dose Effect ◽

Open Label ◽

Anti Vegf

Abstract BACKGROUND Approaches using anti-PD1 therapy alone in rGBM is of limited efficacy. VEGF is upregulated proangiogenic growth factor in GBM that contributes to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF may be a promising approach in rGBM. METHODS 90 patients with GBM at first recurrence were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performance status and MGMT methylation status. Progression-free survival (PFS) and overall survival (OS) were compared between two arms. RESULTS 90 patients (Median age 60.6 years ranged 27.4-86.4, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 patients were MGMT methylated and 53 patients were MGMT not hypermethylated and 2 were indeterminate. Overall Survival was not significantly different between arm A and arm B (1 year: 41.1 vs 37.7%, p=0.14), while OS was better for arm A in age > 60 (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P=0.046). OS was no different in the two arms for age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P=0.90). Most frequent toxicities ( >20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. CONCLUSIONS Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared to historical benchmarks of bevacizumab monotherapy. Nivolumab with standard bevacizumab seem to benefit patients older than 60 years old.

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The point of transition on the dose-effect curve as a reference point in the evaluation of in vitro toxicity data

Journal of Applied Toxicology ◽

10.1002/jat.2757 ◽

2012 ◽

Vol 32 (10) ◽

pp. 843-849 ◽

Cited By ~ 6

Author(s):

Salomon Sand ◽

Joakim Ringblom ◽

Helen Håkansson ◽

Mattias Öberg

Keyword(s):

Reference Point ◽

Dose Effect ◽

In Vitro Toxicity ◽

Toxicity Data ◽

Effect Curve

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A BIOLOGICAL ASSAY FOR CALCITONIN

Journal of Endocrinology ◽

10.1677/joe.0.0330469 ◽

1965 ◽

Vol 33 (3) ◽

pp. 469-475 ◽

Cited By ~ 111

Author(s):

M. A. KUMAR ◽

E. SLACK ◽

A. EDWARDS ◽

H. A. SOLIMAN ◽

A. BAGHDIANTZ ◽

...

Keyword(s):

Satisfactory Agreement ◽

Intravenous Administration ◽

Dose Range ◽

Plasma Calcium ◽

Dose Effect ◽

Biological Assay ◽

Potency Ratio ◽

Standard Preparation ◽

Assay Design ◽

Routine Assay

SUMMARY (1) Calcitonin preparations from acetone-dried thyroid were administered to rats by various routes. (2) Intravenous administration, especially by infusion, produced a much greater fall in plasma calcium than s.c. or i.p. injection. (3) The log dose-effect curves after i.v. injection or infusion showed no evidence of non-linearity over a 100-fold dose range and had highly significant slopes. (4) The potency ratio of two preparations was estimated by means of a (2+2) assay design using both i.v. infusion and single i.v. injection. There was satisfactory agreement. (5) The i.v. injection method is recommended for the routine assay of calcitonin. A simple assay schedule is given in the Appendix. (6) A unit of calcitonin activity is defined in terms of a standard preparation.

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DETERMINATION OF ELECTRON BEAM CHARGING CONDITIONS OF OXIDES AT LOW ENERGY IN THE LOW DOSE RANGE

Le Journal de Physique Colloques ◽

10.1051/jphyscol:1989628 ◽

1989 ◽

Vol 50 (C6) ◽

pp. C6-174-C6-174

Author(s):

M. VALENZA ◽

P. GIRARD ◽

B. PISTOULET

Keyword(s):

Electron Beam ◽

Low Dose ◽

Dose Range ◽

Low Energy

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Research on the Effects of the Extract of Polygala fallax Hemsl on Sex Hormones and ?-EP in Perimenopausal Rat Models

Journal of Clinical and Nursing Research ◽

10.26689/jcnr.v4i3.1235 ◽

2020 ◽

Vol 4 (3) ◽

Author(s):

Siyuan Yang ◽

Zhiyong Cao ◽

Jiabao Chen ◽

Gang Fang

Keyword(s):

Menstrual Cycle ◽

Sex Hormones ◽

Dose Group ◽

Low Dose ◽

Normal Group ◽

Dose Effect ◽

High Dose Group ◽

High Dose ◽

Model Group ◽

Rat Models

Objective: To study the effects of the ethnic medicine Polygala fallax Hemsl with Guangxi characteristics on the sex hormones and ?-EP in research objective perimenopausal rat models. Methods: 40 female SPF rats were randomly divided into 4 groups, including the normal, model, high-dose and low-dose groups. Rats of three groups except for the normal one were treated with perimenopausal modelling through the method of subcutaneous injection of compound 4-VCD for 15 consecutive days. Rats of the normal and model group were normally fed without any treatment. Rats of the high-dose and low-dose groups were administered by high- and low-dose intragastric administration of the extract of Polygala fallax Hemsl. According to the menstrual cycle of the vaginal smear of the rat, each menstrual cycle is a course of treatment and 6 consecutive courses of treatment would be given. The indexes of serum sex hormones (E2, FSH, LH) and ?-EP of rats in each group were observed after treatment. Results: After the treatment of 6 cycles, for the levels of ?-EP and E2, the model group was lowest (P<0.05), the normal group was highest (P<0.05); and the high-dose group was higher than the low-dose group; For the levels of FSH and LH, the normal group was lowest (P<0.05), the model group was highest (P<0.05), and the high-dose group was lower than the low-dose group. Conclusion: Guangxi characteristic national medicine Polygala fallax Hemsl can effectively improve the levels of serum sex hormones and ?-EP in perimenopausal rat models and relieve the related symptoms with a certain dose-effect relationship.

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Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose–effect meta-analysis

The British Journal of Psychiatry ◽

10.1192/bjp.2021.165 ◽

2021 ◽

pp. 1-8

Author(s):

Yuki Furukawa ◽

Tasnim Hamza ◽

Andrea Cipriani ◽

Toshi A. Furukawa ◽

Georgia Salanti ◽

...

Keyword(s):

Meta Analysis ◽

Dose Range ◽

Drop Out ◽

Dose Effect ◽

High Dose ◽

Optimal Dosage ◽

Inadequate Response ◽

Augmentation Therapy ◽

Refractory Depression ◽

Significant Difference

Background Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear. Aims To find the optimal dosage of aripiprazole augmentation. Method Multiple electronic databases were searched (from inception to 16 February 2021) to identify all assessor-masked randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder showing inadequate response to at least one antidepressant treatment. A random-effects, one-stage dose–effect meta-analysis with restricted cubic splines was conducted. Outcomes were efficacy (treatment response: ≥50% reduction in depression severity), tolerability (drop-out due to adverse effects) and acceptability (drop-out for any reason) after 8 weeks of treatment (range 4–12 weeks). Results Ten studies met the inclusion criteria. All were individually randomised, placebo-controlled, multi-centre, parallel studies including 2625 participants in total. The maximum target dose–efficacy curve showed an increase up to doses between 2 mg (odds ratio OR = 1.46, 95% CI 1.15–1.85) and 5 mg (OR = 1.93, 95% CI 1.33–2.81), and then a non-increasing trend through the higher licensed doses up to 20 mg (OR = 1.90, 95% CI 1.52–2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate. Conclusions Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.

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