scholarly journals Pharmacology and similia principle: indirect secondary counter-regulation. Confirmation from in vitro experiments and classical provings

Author(s):  
Andrea Signorini

Homeopathy is universally known as an opponent of allopathic Medicine, namely scientific medicine based on ponderal drugs and recognised mechanisms of receptor agonism and antagonism following the dose-response curve. Over time the difficulty to explain with arguments the action of homeopathic ultra-diluted remedies has led many homeopaths to distance themselves from any pharmacological knowledges. Nevertheless this position fortgets not only the modalities in which homeopathy was born and has grown, but a lot of modern changes of view in body-mind communication, cell communication, neuro-immune-endocrinology and bioelectromagnetism, that could give new reasons to treat as clinical homeopathic practice is teaching and to recognize the principle of similars as a modern pharmacological principle. These arguments, receptorial cell communication, bioelectromagnetism and body-mind unity are the bases of Homeopathy and of the Similia Principle and are all included in embryonic but sufficiently clear considerations in the fundamental book of Hahnemann, the Organon (parr. 11, 13, 15-18, 21, 22, 29-32, 63-70). Two kind of evidences confirm the pharmacological bases of SimiliaPriniciple, in vitro experiments and homeopathic pathogenetic trials on healthy volunteers, best known as provings. Even clinical homeopathic phenomena like initial aggravation and return of old symptoms confirm this pharmacological view of the Simila Principle.

1983 ◽  
Vol 55 (1) ◽  
pp. 22-26 ◽  
Author(s):  
S. Shore ◽  
C. G. Irvin ◽  
T. Shenkier ◽  
J. G. Martin

We studied the effects of atropine (10(-10) to 10(-6) M), tetrodotoxin (TTX) (10(-6) g/ml), and neostigmine (10(-7) M) on the histamine dose-response curve of canine tracheal smooth muscle (TSM) in vitro. Pretreatment with atropine or TTX reduced base-line tension in some TSM samples, whereas neostigmine invariably caused contraction of TSM. All concentrations of atropine reduced the maximum isometric tension produced by histamine (Tmax). With 10(-6), 10(-8), and 10(-10) M atropine, Tmax was 57, 74, and 88%, respectively, of its value in paired control samples. Atropine, 10(-9) to 10(-6) M, increased the concentration of histamine which produced 20% of Tmax, whereas 10(-6) M also increased the concentration required to produce 50% of Tmax. TTX reduced tension produced by low concentrations of histamine but had no effect at higher concentrations. Neostigmine shifted the histamine dose-response curve and caused greater tension for any given histamine concentration; Tmax increased by 30% (P less than 0.05). Our data are consistent with spontaneous release of acetylcholine from cholinergic nerves in the airway tissue and suggest that histamine either accelerates this release or interacts supra-additively with the acetylcholine at the smooth muscle.


1999 ◽  
Vol 190 (10) ◽  
pp. 1383-1392 ◽  
Author(s):  
Martin F. Bachmann ◽  
Marijke Barner ◽  
Manfred Kopf

It has been proposed that CD2, which is highly expressed on T cells, serves to enhance T cell–antigen presenting cell (APC) adhesion and costimulate T cell activation. Here we analyzed the role of CD2 using CD2-deficient mice crossed with transgenic mice expressing a T cell receptor specific for lymphocytic choriomeningitis virus (LCMV)-derived peptide p33. We found that absence of CD2 on T cells shifted the p33-specific dose–response curve in vitro by a factor of 3–10. In comparison, stimulation of T cells in the absence of lymphocyte function–associated antigen (LFA)-1–intercellular adhesion molecule (ICAM)-1 interaction shifted the dose–response curve by a factor of 10, whereas absence of both CD2–CD48 and LFA-1–ICAM-1 interactions shifted the response by a factor of ∼100. This indicates that CD2 and LFA-1 facilitate T cell activation additively. T cell activation at low antigen density was blocked at its very first steps, as T cell APC conjugate formation, TCR triggering, and Ca2+ fluxes were affected by the absence of CD2. In vivo, LCMV-specific, CD2-deficient T cells proliferated normally upon infection with live virus but responded in a reduced fashion upon cross-priming. Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4149-4149
Author(s):  
Harry L. Messmore ◽  
Nancy J. Fabbrini ◽  
Ketty Badrinath ◽  
Richard Harriman ◽  
Omar Iqbal ◽  
...  

Abstract The direct thrombin inhibitors lepirudin and argatroban are widely used to treat heparin induced thrombocytopenia (HIT). It has been suggested that the Ecarin™ (Echis carinatus venom) clotting time may be superior to the activated partial thromboplastin time (APTT) for monioring purposes. We have prepared standard curves for lepirudin (Refludan™) and Argatroban covering therapeutic drug levels and corresponding APTT ratios (clotting time/control clotting time). Ecarin™ clotting time ratios were performed to demonstrate the practical application of these curves in the clinical care of patients. We report the case of an 80 year old man with HIT/HITT syndrome that occurred during therapy for deep vein thrombosis (DVT) with a low molecular weight heparin (LMWH). His initial coagulation studies were abnormal due to warfarin and LMWH therapy. The patient had a moderate impairment of renal function. Lepirudin therapy in a bolus dose of 14 mg (patient weight: 103.0 kg) resulted in supratherapeutic blood levels of drug and hematuria (Platelet count: 〉200 x 103). Dosage adjustment to maintain an APTT ratio of 1.5 for five days caused no hematuria, but thromboembolic complications occurred at that ratio. The in-vitro dose response curve for Lepirudin was compared with the Ecarin™ clotting time (ECT) ratio at those same concentration ranges in the same plasma. For comparison, Argatroban dose response curves in-vitro were made as well. ECT ratios were very similar to the APTT ratios in the patient’s samples. Representative ratios after the initial bolus, during the infusion period of five days and at the termination of that period are shown in the following table: Comparison of APTT and ECT Ratios APTT Ratio ECT Ratio 1.43 1.07 3.98 3.08 2.91 1.95 2.74 1.95 2.79 1.90 2.58 1.78 2.44 2.42 3.83 4.78 Conclusion: The ECT ratios reflect a steeper dose response curve than that observed with the APTT ratios. This may permit more accurate measurement of blood levels using ECT ratios.


2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Antonio Carlo D. De Guzman ◽  
Carmencita D. Padilla ◽  
Henri Cartier S. Co ◽  
Elrick T. Inocencio ◽  
Edsel Allan G. Salonga

Background. Accidental radiation exposure can occur anytime. Biodosimeters help in quantifying the absorbed dose of individuals who are not equipped with personal dosimeters during radiation exposure. The dicentric assay can quantify radiation damage by correlating radiation dose exposure with the frequency of dicentric chromosomes in the peripheral lymphocytes extracted from exposed individuals. Objective. The study aims to present the interim results of the reference dose-response curve for a Philippine radiotherapy facility constructed using a 6MV linear accelerator (ClinacX, Varian). Methods. Samples of peripheral blood from healthy volunteers were irradiated in a customized water phantom of doses 0.10 to 5.0 Gray using a linear accelerator. The irradiated samples were cultured and analyzed following the International Atomic Energy Agency Cytogenetic Dosimetry Protocol (2011) with modifications. Linear-quadratic model curve fitting and further statistical analysis were done using CABAS (Chromosome Aberration Calculation Software Version 2.0) and Dose Estimate (Version 5.2). Interim results of the samples were used to generate these curves. Results. The dose-response curve generated from the preliminary results were comparable to published dose response curves from international cytogenetic laboratories. Conclusion. The generated dose-response calibration curve will be useful for medical triage of the public and radiologic staff accidentally exposed to radiation during medical procedures or in the event of nuclear accidents.


Author(s):  
Enrique Castano ◽  
Ruben D Flores-Saaib

Several reports over the last few years have documented the dose–response curve for steroid hormone induction of gene transcription as a modulated property of a given receptor–agonist complex that varies with the changing concentration of a variety of factors including: homologous receptor, co-activators, co-repressors and selected co-factors. In each report, the dose–response curves are sigmoidal and show an excellent fit with the curve generated by Michaelis–Menten kinetics. In addition, even the overall function of human oestrogen receptors (hERs) can show a similar graph for the determination of sex versus oestrogen compounds in reptiles. Thus, the kinetic properties of the simple bimolecular reaction of A+B→C appear, surprisingly, to be sufficient to describe the dose–response curve of the multi-step process of steroid-regulated gene induction that involves several molecules. Any advance in explaining why the dose–response curve for steroid-regulated gene expression is sigmoidal would assist in understanding what parameters are key factors of the dose–response curve and can benefit in the design of new oestrogenic substances. We have constructed and analysed a multi-step model of hER-induced gene transcription that explains the multiple forms of a simple dose–response curve in an in vitro transcription system.


1958 ◽  
Vol 107 (2) ◽  
pp. 211-218 ◽  
Author(s):  
Melvin M. Ketchel ◽  
Cutting B. Favour ◽  
Somers H. Sturgis ◽  

Hydrocortisone inhibits the ameboid migration of human leucocytes when added in vitro. The dose-response curve for the reaction between this steroid and leucocytes can be best expressed by a logarithmic plot of the steroid concentrations. Tetrahydrocortisone and desoxycorticosterone had no effect on in vitro leucotyte migration.


1975 ◽  
Vol 53 (5) ◽  
pp. 452-455 ◽  
Author(s):  
Robert Hall

Small but significant (P = 0.05) differences in sensitivity to benomyl in vitro were observed among collections of Verticillium dahliae (21 isolates), V. albo-atrum (9 isolates), and V. nigrescens (8 isolates). Mean species effective dose (milligrams per liter) (ED50) values were, respectively, 0.36, p.26, and 0.19 (significantly different from one another). The corresponding mean species values for the slope of the probit inhibition – log dose curve were 10.55, 12.55 (not significantly different), and 6.87 (significantly different). However, positive identification of an isolate by its ED50 value or the slope of the dose–response curve was not possible because of overlap in the range of values within species.


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