scholarly journals THE ADDITIVITY ANTINOCICEPTIVE INTERACTIONS BETWEEN DICLOFENAC AND THE DERRIS SCANDENS EXTRACT DRUG IN MICE.

2018 ◽  
Vol 11 (1) ◽  
pp. 314
Author(s):  
Tadsanee Punjanon
Keyword(s):  
Acetic Acid ◽  
Side Effects ◽  
Combination Therapy ◽  
Dose Response ◽  
Pain Treatment ◽  
Fixed Ratio ◽  
Drug Dose ◽  
Response Curves ◽  
Interaction Index ◽  
Abdominal Constriction

 Objective: Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. The objective was to determine the effects of coadministered diclofenac and the Derris scandens extract drug.Methods: Acetic acid-induced abdominal constriction test in mice was used to determine the type of interaction between components. The effective dose that produced 50% antinociception (ED50) was calculated from the log dose-response curves of fixed ratio combinations of diclofenac with the D. scandens extract drug. The ED50 was compared to the theoretical additive ED50 calculated from the ED50 of diclofenac and of the D. scandens extract drug alone.Results: Diclofenac and the D. scandens extract drug dose‐dependently and significantly reduced the abdominal writhing. The combination was the additive effect, the experimental ED50 being smaller than the theoretically calculated ED50. Interaction index of the combination was 0.89.Conclusion: The present study demonstrates the additivity antinociceptive interactions between diclofenac and the D. scandens extract drug and may be used as a combination analgesic in the treatment of pain conditions.

scholarly journals THE ADDITIVITY ANTINOCICEPTIVE INTERACTIONS BETWEEN DICLOFENAC AND THE DERRIS SCANDENS EXTRACT DRUG IN MICE.

2018 ◽  
Vol 11 (1) ◽  
pp. 314
Author(s):  
Tadsanee Punjanon
Keyword(s):  
Acetic Acid ◽  
Side Effects ◽  
Combination Therapy ◽  
Dose Response ◽  
Pain Treatment ◽  
Fixed Ratio ◽  
Drug Dose ◽  
Response Curves ◽  
Interaction Index ◽  
Abdominal Constriction

 Objective: Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. The objective was to determine the effects of coadministered diclofenac and the Derris scandens extract drug.Methods: Acetic acid-induced abdominal constriction test in mice was used to determine the type of interaction between components. The effective dose that produced 50% antinociception (ED50) was calculated from the log dose-response curves of fixed ratio combinations of diclofenac with the D. scandens extract drug. The ED50 was compared to the theoretical additive ED50 calculated from the ED50 of diclofenac and of the D. scandens extract drug alone.Results: Diclofenac and the D. scandens extract drug dose‐dependently and significantly reduced the abdominal writhing. The combination was the additive effect, the experimental ED50 being smaller than the theoretically calculated ED50. Interaction index of the combination was 0.89.Conclusion: The present study demonstrates the additivity antinociceptive interactions between diclofenac and the D. scandens extract drug and may be used as a combination analgesic in the treatment of pain conditions.

Differential temperature dependence of taste nerve responses to various taste stimuli in dogs and rats

1991 ◽  
Vol 261 (6) ◽  
pp. R1402-R1408 ◽  
Author(s):  
M. Nakamura ◽  
K. Kurihara
Keyword(s):  
Acetic Acid ◽  
Temperature Dependence ◽  
Temperature Change ◽  
Dose Response ◽  
Monosodium Glutamate ◽  
Taste Receptor ◽  
Chorda Tympani ◽  
Chorda Tympani Nerve ◽  
Response Curves ◽  
Tonic Response

The temperature dependence of the canine and rat chorda tympani nerve responses to various taste stimuli was examined. The temperature dependence greatly varied with species of stimuli. In the dog, the tonic responses to fructose, sucrose, acetic acid, and guanosine 5'-monophosphate (GMP) and the response induced by the synergism between monosodium glutamate (MSG) and GMP showed peaks at approximately 30 degrees C, whereas those to NaCl, NH4Cl, and MSG showed peaks between 10 and 20 degrees C. In the rat, the tonic response to NH4Cl increased with an increase in temperature up to 45 degrees C, whereas the responses to other stimuli examined showed peaks at approximately 30 degrees C. The responses to glycine, sucrose, and quinine showed sharp temperature dependence, and the responses to acids (HCl and acetic acid) and salts (NaCl and KCl) showed relatively flat dependence. The effects of the temperature change on dose-response curves for fructose, NH4Cl, and GMP were examined using dogs. The temperature change did not practically affect the thresholds for these stimuli and affected the magnitude of the responses to higher concentrations of stimuli. The origins of the temperature dependence were discussed in terms of taste receptor mechanisms.

scholarly journals The effect of auxins (IAA and 4-Cl-IAA) on the redox activity and medium pH of Zea mays L. root segments

2006 ◽  
Vol 11 (3) ◽  
Author(s):  
Halina Lekacz ◽  
Waldemar Karcz
Keyword(s):  
Acetic Acid ◽  
Dose Response ◽  
Zea Mays L ◽  
Response Surfaces ◽  
Redox Activity ◽  
Response Curves ◽  
Medium Ph ◽  
Ph Changes ◽  
Root Segments ◽  
Indole 3 Acetic Acid

AbstractIndole-3-acetic acid (IAA) and 4-chloroindole-3-acetic acid (4-Cl-IAA) were tested at different concentrations and times for their capacity to change the redox activity and medium pH of maize root segments. The dose-response surfaces (dose-response curves as a function of time) plotted for redox activity and changes in medium pH (expressed as ΔpH) had a similar shape for both auxins, but differed significantly at the optimal concentrations. With 4-Cl-IAA, the maximal values of redox activity and medium pH changes were observed at 10−10 M, which was a 100-fold lower concentration than with IAA. Correlations were observed between redox activity and medium pH changes at the optimal concentrations of both IAA and 4-Cl-IAA. The results are discussed herein, taking into account both the concentration of the auxins and the effects produced by them.

scholarly journals Side Effects of Nitrification Inhibitors on Non Target Microbial Processes in Soils

2013 ◽  
Vol 16 (1) ◽  
pp. 7-16
Author(s):  
Ferisman Tindaon ◽  
Gero Benckiser ◽  
Carl Gottlieb Ottow
Keyword(s):  
Side Effects ◽  
Dose Response ◽  
Nitrogenase Activity ◽  
Microbial Processes ◽  
Nitrification Inhibitors ◽  
Silty Clay ◽  
Response Curves ◽  
Potential Denitrification ◽  
Toxicological Studies ◽  
Dimethylsulfoxide Reductase

Agricultural chemicals have been used extensively in modern agriculture and toxicological studies suggest a great potential for inducing undesirable effects on non target organisms. A model experiment was conducted in order to determine side effects of three nitrification inhibitors (NIs, 3,4dimethylpyrazolephosphate = DMPP, 4-Chlormethylpyrazole phosphate = ClMPP and dicyandiamide = DCD) on non target microbial processes in soils. Side effects and dose response curve of three NIs were quantified under laboratory conditions using silty clay, loam anda sandy soils. Dehydrogenase, dimethylsulfoxide reductase as well as nitrogenase activity (NA) and potential denitrification capacity were measured as common and specific non target microbial processes. The influence of 5-1000 times the base concentration, dose response curves were examined, and no observable effect level = NOEL, as well as effective dose ED10 and ED50 (10% and 50% inhibition) were calculated. The NOEL for microbial non target processes were about 30–70 times higher than base concentration in all investigated soils. The potential denitrification capacity revealed to be the most sensitive parameter. ClMPP exhibited the strongest influence on the non target microbial processes in the three soils. The NOEL, ED10 and ED50 values were higher in clay than in loamy or sandy soil. The NIs was the most effective in sandy soils.Keywords: microbial non target processes, nitrification inhibitors, soil enzymes

scholarly journals Different Patterns of Mast Cell Activation by Muscle Relaxants in Human Skin

2001 ◽  
Vol 95 (3) ◽  
pp. 659-667 ◽  
Author(s):  
Wolfgang Koppert ◽  
James A. Blunk ◽  
Lars J. Petersen ◽  
Per Skov ◽  
Katharina Rentsch ◽  
...  
Keyword(s):  
Mast Cell ◽  
Side Effects ◽  
Dose Response ◽  
Cell Activation ◽  
Muscle Relaxants ◽  
Mediator Release ◽  
Mast Cell Activation ◽  
Response Curves ◽  
Sensory Effects ◽  
Dose Response Curves

Background Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects. Methods Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves. Results For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase. Conclusions Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.

Experimental design and statistical analysis for three-drug combination studies

2015 ◽  
Vol 26 (3) ◽  
pp. 1261-1280 ◽  
Author(s):  
Hong-Bin Fang ◽  
Xuerong Chen ◽  
Xin-Yan Pei ◽  
Steven Grant ◽  
Ming Tan
Keyword(s):  
Experimental Design ◽  
Dose Response ◽  
Drug Combination ◽  
Mathematical Reasoning ◽  
Experimental Studies ◽  
Drug Combinations ◽  
Dose Finding ◽  
Nonparametric Model ◽  
Response Curves ◽  
Interaction Index

Drug combination is a critically important therapeutic approach for complex diseases such as cancer and HIV due to its potential for efficacy at lower, less toxic doses and the need to move new therapies rapidly into clinical trials. One of the key issues is to identify which combinations are additive, synergistic, or antagonistic. While the value of multidrug combinations has been well recognized in the cancer research community, to our best knowledge, all existing experimental studies rely on fixing the dose of one drug to reduce the dimensionality, e.g. looking at pairwise two-drug combinations, a suboptimal design. Hence, there is an urgent need to develop experimental design and analysis methods for studying multidrug combinations directly. Because the complexity of the problem increases exponentially with the number of constituent drugs, there has been little progress in the development of methods for the design and analysis of high-dimensional drug combinations. In fact, contrary to common mathematical reasoning, the case of three-drug combinations is fundamentally more difficult than two-drug combinations. Apparently, finding doses of the combination, number of combinations, and replicates needed to detect departures from additivity depends on dose–response shapes of individual constituent drugs. Thus, different classes of drugs of different dose–response shapes need to be treated as a separate case. Our application and case studies develop dose finding and sample size method for detecting departures from additivity with several common (linear and log-linear) classes of single dose–response curves. Furthermore, utilizing the geometric features of the interaction index, we propose a nonparametric model to estimate the interaction index surface by B-spine approximation and derive its asymptotic properties. Utilizing the method, we designed and analyzed a combination study of three anticancer drugs, PD184, HA14-1, and CEP3891 inhibiting myeloma H929 cell line. To our best knowledge, this is the first ever three drug combinations study performed based on the original 4D dose–response surface formed by dose ranges of three drugs.

An isobolographic analysis of the anti-nociceptive effect of geraniin in combination with morphine or diclofenac

2018 ◽  
Vol 29 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Eric Boakye-Gyasi ◽  
Ella Anle Kasanga ◽  
Elvis Ofori Ameyaw ◽  
Wonder Kofi Mensah Abotsi ◽  
Robert Peter Biney ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Aqueous Extract ◽  
Dose Response ◽  
Formalin Test ◽  
Fixed Ratio ◽  
Test Dose ◽  
Response Curves ◽  
Isobolographic Analysis ◽  
Aerial Parts

AbstractBackground:Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts ofPhyllanthus muellerianus(Kuntze) Exell. (Euphorbiaceae). SeveralPhyllanthusspecies are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts ofP. muellerianusand of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects.Methods:The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3–30 mg/kg), morphine (1–10 mg/kg), and diclofenac (10–100 mg/kg) to obtain the ED50values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50values for the formalin test.Results:Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test.Conclusions:The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac.

scholarly journals The ENDS of assumptions; an online tool for the Epistemic Nonparametric Drug-response Scoring

2021 ◽  
Author(s):  
Ali Amiryousefi ◽  
Bernardo Williams ◽  
Mohieddin Jafari ◽  
Jing Tang
Keyword(s):  
Dose Response ◽  
Curve Fitting ◽  
Drug Response ◽  
Drug Dose ◽  
Supplementary Information ◽  
Response Curves ◽  
Source Codes ◽  
Nonparametric Models ◽  
Link Type ◽  
Objective Representation

AbstractMotivationThe drugs sensitivity analysis is often elucidated from drug dose-response curves. These curves capture the degree of cell viability (or inhibition) over a range of induced drugs, often with parametric assumptions that are rarely validated.ResultsWe present a class of nonparametric models for the curve fitting and scoring of drug dose-responses. To allow a more objective representation of the drug sensitivity, these epistemic models devoid of any parametric assumptions attached to the linear fit, allow the parallel indexing such as IC50 and AUC. Specifically, three nonparametric models including Spline, Monotonic, and Bayesian (npS, npM, npB) and the parametric Logistic (pL) are implemented. Other indices including Maximum Effective Dose (MED) and Drug-response Span Gradient (DSG) pertinent to the npS are also provided to facilitate the interpretation of the fit. The collection of these models are implemented in an online app, standing as useful resource for drug dose-response curve fitting and analysis.AvailabilityThe ENDS is freely available online at https://irscope.shinyapps.io/ENDS/ and source codes can be obtained from https://github.com/AmiryousefiLab/ENDS.Supplementary informationSupplementary data are available at Bioinformatics and https://irscope.shinyapps.io/ENDS/[email protected]; [email protected] conceived the study and developed the models, AA and BW adopted and implemented the methods, JT provided the funding, AA, BW, MJ, and JT wrote the paper.

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