dose range
Recently Published Documents


TOTAL DOCUMENTS

1688
(FIVE YEARS 451)

H-INDEX

82
(FIVE YEARS 9)

2022 ◽  
Vol 8 ◽  
Author(s):  
Kirsten M. Wright ◽  
Janis McFerrin ◽  
Armando Alcázar Magaña ◽  
Joanne Roberts ◽  
Maya Caruso ◽  
...  

Botanical products are frequently sold as dietary supplements and their use by the public is increasing in popularity. However, scientific evaluation of their medicinal benefits presents unique challenges due to their chemical complexity, inherent variability, and the involvement of multiple active components and biological targets. Translation away from preclinical models, and developing an optimized, reproducible botanical product for use in clinical trials, presents particular challenges for phytotherapeutic agents compared to single chemical entities. Common deficiencies noted in clinical trials of botanical products include limited characterization of the product tested, inadequate placebo control, and lack of rationale for the type of product tested, dose used, outcome measures or even the study population. Our group has focused on the botanical Centella asiatica due to its reputation for enhancing cognition in Eastern traditional medicine systems. Our preclinical studies on a Centella asiatica water extract (CAW) and its bioactive components strongly support its potential as a phytotherapeutic agent for cognitive decline in aging and Alzheimer's disease through influences on antioxidant response, mitochondrial activity, and synaptic density. Here we describe our robust, scientific approach toward developing a rational phytotherapeutic product based on Centella asiatica for human investigation, addressing multiple factors to optimize its valid clinical evaluation. Specific aspects covered include approaches to identifying an optimal dose range for clinical assessment, design and composition of a dosage form and matching placebo, sourcing appropriate botanical raw material for product manufacture (including the evaluation of active compounds and contaminants), and up-scaling of laboratory extraction methods to available current Good Manufacturing Practice (cGMP) certified industrial facilities. We also address the process of obtaining regulatory approvals to proceed with clinical trials. Our study highlights the complexity of translational research on botanicals and the importance of identifying active compounds and developing sound analytical and bioanalytical methods for their determination in botanical materials and biological samples. Recent Phase I pharmacokinetic studies of our Centella asiatica product in humans (NCT03929250, NCT03937908) have highlighted additional challenges associated with designing botanical bioavailability studies, including specific dietary considerations that need to be considered.


2022 ◽  
Author(s):  
Ulyana Bliznyuk ◽  
Natalya Chulikova ◽  
Anna Malyuga

Crops, especially potatoes, are prone to a wide range of fungal, viral and bacterial diseases, including black scurf caused by Rhizoctoniasolani. This study focused on the radiation treatment of the phytopathogenic fungus RhizoctoniasolaniKuhn, grown from sclerotium irradiated with 1 MeV electrons in the dose range from 20 to 4500 Gy. The doses absorbed by the sclerotia were determined using computer simulation. The growth of the fungus samples was monitored after 24, 48, 72, and 96 hours from the time of seeding. It was found that the dependence of the radial growth velocity of R. solani on the time after irradiation with doses ranging from 20to 1800 Gywas nonlinear. Irradiation at a dose over 4500 Gyled to complete suppression of the germination of R. solani sclerotia. Keywords: radiation treatment, electron radiation, radiation dose, sclerotia of Rhizoctoniasolani, Kuhn, radial velocity of growth


2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Ekaterina Chirikova ◽  
Robert J. McConnell ◽  
Patrick O’Kane ◽  
Vasilina Yauseyenka ◽  
Mark P. Little ◽  
...  

Abstract Background While there is a robust literature on environmental exposure to iodine-131 (131I) in childhood and adolescence and the risk of thyroid cancer and benign nodules, little is known about its effects on thyroid volume. Methods To assess the effect of 131I dose to the thyroid on the volume of the thyroid gland, we examined the data from the baseline screening of the Belarusian-American Cohort Study of residents of Belarus who were exposed to the Chernobyl fallout at ages ≤18 years. Thyroid dose estimates were based on individual thyroid activity measurements made shortly after the accident and dosimetric data from questionnaires obtained 10-15 years later at baseline screening. During baseline screening, thyroid gland volume was assessed from thyroid ultrasound measurements. The association between radiation dose and thyroid volume was modeled using linear regression where radiation dose was expressed with power terms to address non-linearity. The model was adjusted for attained age, sex, and place of residence, and their modifying effects were examined. Results The analysis was based on 10,703 subjects. We found a statistically significant positive association between radiation dose and thyroid volume (P < 0.001). Heterogeneity of association was observed by attained age (P < 0.001) with statistically significant association remaining only in the subgroup of ≥18 years at screening (P < 0.001). For this group, increase in dose from 0.0005 to 0.15 Gy was associated with a 1.27 ml (95% CI: 0.46, 2.07) increase in thyroid volume. The estimated effect did not change with increasing doses above 0.15 Gy. Conclusions This is the first study to examine the association between 131I dose to the thyroid gland and thyroid volume in a population of individuals exposed during childhood and systematically screened 10-15 years later. It provides evidence for a moderate statistically significant increase in thyroid volume among those who were ≥ 18 years at screening. Given that this effect was observed at very low doses and was restricted to a narrow dose range, further studies are necessary to better understand the effect.


2022 ◽  
Author(s):  
Shanker Kalakotla ◽  
Geetha P ◽  
Ahmadi Banu ◽  
Shamshe Shaik

Abstract Diabetes is among the most common debilitating and non-transferable diseases on the planet. The idea of using nanoparticles as a drug to treat diabetes mellitus seems intriguing. The Ag nanoparticles (Ag NPs) were effectively produced utilizing Moringa olifera (family: Moringaceae) plant extract employing a simple, cheaper, faster, and environmentally friendly green synthesis process. The antidiabetic effect of the produced Ag NPs was also tested in vivo. In the presence of plant extract, silver nitrate was converted to silver ions (Ag). XRD, FTIR, UV, XPS, and HRTEM studies characterize the formed Ag NPs. Ag NPs that have been biosynthesized, crystal nature was confirmed through XRD analysis and confirmed by UV-visible spectroscopy. FT-IR spectra were used to verify the presence of various functional groups in the biomolecules, forming and stabilizing the nanoparticles. The size of the NPS was in the range of 20-40 nm determined by HRTEM. The induction of diabetes using STZ showed increased blood glucose, cholesterol, triglycerides, LDL, VLDL, massive loss in body weight. These changes were reversed following the treatment of diabetic rats for 28 days and showed significant inhibition (p < 0.001) at a dose range of 0.2 mg/kg leaf extract and 0.2 mg/kg Ag NPs compared with the extract-treated group. These obtained results suggested that plant-mediated Ag NPs have shown promising antidiabetic and anti-hyperlipidemic activity compared to the crude extract.


Author(s):  
Encep Abdurahman ◽  
Nengdiana Permana ◽  
Grace S. Mardiana ◽  
Afifah B. Sutjiatmo ◽  
Anna Choirunnisa ◽  
...  

Psoriasis is an autoimmune disease that is characterized by the appearance of lesions on the skin. The current treatment aims to control the symptoms. The efficacy of Stachytarpheta jamaicensis (L.) Vahl’s for autoimmune rheumatoid arthritis and systemic lupus erythematosus has been tested in animal models. The aim of this research was to evaluate the effect of the water extract of S. jamaicensis leaves on psoriasis model animal (male Balb/c mice) induced topically by imiquimod. The water extract of S. jamaicensis leaves is made by boiling. The animal was divided into groups: normal, control, methotrexate 0.2 mg/kgBW, the extract (doses 25, 50 and 100 mg/kgBW). The measured parameters were the Psoriasis Area and Severity Index (PASI) score and skin histopathology. The results showed that all doses of the extract could reduce the PASI score when compared to the control group. Histological results showed that there was a decrease in keratin growth in test animals that were given the extract. Extracts at doses of 25 and 50 mg/kgBW can reduce the thickening of keratin in the epidermis of the back and ears. It can be concluded that the water extract of S. jamaicensis leaf has the most effective activity to prevent psoriasis recurrence in the dose range of 25 and 50 mg/kgBW.Keywords: Psoriasis, Stachytarpheta jamaicensis leaf water extract, PASI, keratin, imiquimod


2022 ◽  
Vol 12 ◽  
Author(s):  
Won-Ho Kang ◽  
Hyo-Jeong Ryu ◽  
Seongsung Kwak ◽  
Hwi-Yeol Yun

In recent, Botulinum Neurotoxin A1 (BoNT/A1) has been suggested as a potential anticancer agent due to neuronal innervation in tumor cells. Although potential BoNT/A1’s mechanism of action for the tumor suppression has been gradually revealed so far, there were no reports to figure out the exposure-response relationships because of the difficulty of its quantitation in the biological matrix. The main objectives of this study were to measure the anticancer effect of BoNT/A1 using a syngeneic mouse model transplanted with melanoma cells (B16-F10) and developed a kinetic-pharmacodynamic (K-PD) model for quantitative exposure-response evaluation. To overcome the lack of exposure information, the K-PD model was implemented by the virtual pharmacokinetic compartment link to the pharmacodynamic compartment of Simeoni’s tumor growth inhibition model and evaluated using curve-fitting for the tumor growth-time profile after intratumoral injection of BoNT/A1. The final K-PD model was adequately explained for a pattern of tumor growth depending on represented exposure parameters and simulation studies were conducted to determine the optimal dose under various scenarios considering dose strength and frequency. The optimal dose range and regimen of ≥13.8 units kg−1 once a week or once every 3 days was predicted using the final model in B16-F10 syngeneic model and it was demonstrated with an extra in-vivo experiment. In conclusion, the K-PD model of BoNT/A1 was well developed to optimize the dosing regimen for evaluation of anticancer effect and this approach could be expandable to figure out quantitative interpretation of BoNT/A1’s efficacy in various xenograft and/or syngeneic models.


2022 ◽  
pp. 1-10
Author(s):  
K. Yousefi ◽  
K.N. Ramdas ◽  
J.G. Ruiz ◽  
J. Walston ◽  
H. Arai ◽  
...  

Background: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 (“mild”) or 6 (“moderate”), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.


2022 ◽  
Vol 951 (1) ◽  
pp. 012106
Author(s):  
R Sriwati ◽  
T Chamzurni ◽  
F Razi ◽  
Syaifullah ◽  
Yunita ◽  
...  

Abstract To increase plant resistance from an early age, it is necessary to introduce biological control agents from groups of fungi and bacteria. This study aims to determine the effect of Trichoderma harziaunum and Bacillus thuringiensis Aceh isolates in increasing the superiority of Aceh patchouli plants that are resistant to pests and plant diseases. The study used non-factorial RAL method with cover and uncovered seedling methods. Both series were treated with the same biological control agent, the control without any treatment, the treatment of T. harzianum and B. thuringiensis while the observations were made when the seedling covered was opened. Observations included plant morphological characters, plant growth development and peroxidase enzymes. The results showed that morphologically the original patchouli growing in Lhoong district had similar morphological characters to the Lhokseumawe variety. The application of biological control agents of the T. harzianum and B. thuringiensis groups was more effective in increasing plant growth in the closed seedling treatment compared to the uncovered seedling. T. harzianum gave the best effect at a dose range of 1-1.5 while B. thuringensis showed a better effect at a concentration of 10-15 ml. Both treatments increased the growth of patchouli seedlings as indicated by the better plant height and number of shoots. Furthermore, higher peroxidation enzymes were found in the closed seedling treatment with 1.5 g T harzianum and 15 ml B. thuringiensis. The high peroxidase enzyme as an indicator of the more resistant plants have been induced to pests and diseases. From the screen house experiment, T. harzianum and B. thuringiensis were more efficient in inducing plant growth and disease resistance of local varieties of patchouli using the closed seedling method.


2021 ◽  
Vol 50 (12) ◽  
pp. 3481-3491
Author(s):  
Fifika Asrapil Waitul ◽  
Mohd Ikmal Asmuni ◽  
Faiz Ahmad ◽  
Noraishah Hasan ◽  
Abdul Rahim Harun ◽  
...  

The carbon ion-beam has emerged as a novel physical mutagen for creating genetic variability and crop improvement. In this study, seeds of a high-yielding pyramided rice line MR219-PL-5 were exposed to carbon ion beam irradiation at 10, 20, 40, 60, 80, and 100 Gy. The radiosensitivity test was conducted to determine the optimum dose of carbon ion beam irradiation based on the lethal dose 50% (LD50) using Sandwich Blotter Technique. The biological responses of carbon-ion beam irradiation were also observed in other characteristics such as germination rate (GeR), survival rate (SR), growth rate (GRoR), shoot length (SL), root length (RL), seedling height (SH), days to flowering (DTF), fertility rate (FR) and thousand-grains weight (TGW). Based on the polynomial curve of SR graph, the lethal dose 50% (LD50) value was 86.12 Gy. However, the optimum dose range of carbon ion-beam irradiation was between 40 and 60 Gy as these two doses recorded the highest SR, 63 and 67%, respectively. Furthermore, the shoulder dose in this study was 60 Gy since SR decreased significantly at higher doses. M1 individuals irradiated at 40 and 60 Gy had the best biological responses where significant differences were found for SR, SL, RL, GRoR, SH, DTF and FR at these two doses compared to the other doses. Further studies on M2 and M3 populations could help to identify potential individuals as well as to understand the inheritance of each trait of interest from one generation to the next.


2021 ◽  
Vol 18 ◽  
Author(s):  
Xi-Yu Wei ◽  
Zhen-Zhen Zhang ◽  
Tao Xie ◽  
Yue-Sheng Xie ◽  
Yue Sun ◽  
...  

Background: Rabdosia rubescens drop pills have the effects of clearing away heat and toxin, detumescence, relieving pain. Objective: A simple and sensitive method for simultaneous determination of oridonin, ponicidin, and rosmarinic acid in rat plasma was developed based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Methods: Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) with a mobile phase consisting of water containing 0.2% formic acid (mobile phase A) and methanol (mobile phase B) at a flow rate of 0.3 mL/min over a total run time of 3.8 min. All analytes were measured with optimized multiple reaction monitoring (MRM) in positive and negative ion ESI mode. Results: The transitions of oridonin, ponicidin, rosmarinic acid, diphenhydramine, and chloramphenicol were 365.3→347.3, 363.3→345.2, 359.0→160.9, 256.0→167.2, and 321.1→151.9, respectively. The linear ranges were 1-256 ng/mL for ponicidin and rosmarinic acid and 2-512 ng/mL for oridonin. The validated method wasstable and reliable. There was no significant difference in the half-life (t1/2) of the three analytes at three doses. The area under the curve (AUC0-t) and peak concentration (Cmax) of the three analytes decreased linearly in each dose range, and the linear correlation R2 of each analyte under the three doses was greater than 0.95. Conclusion: This method was successfully applied to pharmacokinetic studies of oridonin, ponicidin, and rosmarinic acid in rat plasma after intragastric administration of Rabdosia rubescens drop pills.


Sign in / Sign up

Export Citation Format

Share Document