Ultra low doses: Biological and clinical applications

ULTRA LOW DOSES

Ultra Low Doses Edited by C. Doutremepuich Université Bordeaux France

Taylor & Francis London · Washington, DC 1991

UK Taylor & Francis Ltd., 4 John St. London WC1N 2ET USA Taylor & Francis Inc., 1900 Frost Road, Suite 101, Bristol, PA 19007 This edition published in the Taylor & Francis e-Library, 2005. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.” Copyright © Taylor & Francis Ltd., 1991 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owners. British Library Cataloguing in Publication Data Available on request Library of Congress Cataloging-in-Publication Data Available on request ISBN 0-203-48143-7 Master e-book ISBN

ISBN 0-203-78967-9 (Adobe eReader Format)

Contents

Preface

I EXPERIMENTAL PHARMACOLOGY First experimental arguments in favor of the effect of very weak doses of copper on digestive motricity in mice and rabbits Santini, R.Tessier, M.Belon, P.Pacheco, H.

2

The effects of some regulatory peptides in femtomolar and lower concentrations on the contraction of lymphatic vessels (LVs) Ashmarin, I.P.Levekova, L.Ts.Sanzhieva.

9

Modulation of experimental rat liver carcinogenesis by ultra low doses of the carcinogens De Gerlache, J.Lans, M.

14

Overcoming tumor cell drug resistance by low doses of recombinant tumor necrosis factor and drug Bonavida, B.Safrit, J.Tsuchitani, T.Zighelboim, J.

22

Effect of acetylsalicylic acid at ultra low dose on the interaction platelets/ vessel wall Lalanne, M.C.De Seze, O.Doutremepuich, C.

36

II BIOPHYSICS A quantum chemical study of some model anti-inflammatory compounds: the preferred conformations and their electrostatic similarities Bhattacharjee, Apurka, K.

44

Influence of several physical factors on the activity of ultra low doses Cazin, J.C.Cazin, M.Chaoui, A.Belon, P.

55

v

III BIOCHEMISTRY—TOXICOLOGY Uranyl nitrate induced corpuscular derangement in rat, an early indication of renel dysfunctioning Gojer, M.Sawant, V.

66

Degranulation of mesenteric mast cells as ‘spot test’ in toxicology Rathinam, K.Mohanan, P.V.Lizzy Michael

72

IV CELL BIOLOGY Simultaneous measurement of oxidative metabolism and adhesion of human neutrophils and evaluation of multiple doses of agonists and inhibitors Bellavite, P.Chirumbolo, S.Signorini, A.Bianchi, I.Dri, P.

76

Non-stimulatory concentrations of concanavalin A can modulate subsequent stimulation by the same mitogen Eskinazi, D.P.Molinaro, G.A.

95

Biological activity of ultra low doses: I/Effect of ultra low doses of histamine on human basophil degranulation triggered by D. pteronyssinus extract Sainte-Laudy, J.Sambucy, J.L.Belon, P.

101

Biological activity of ultra doses: II/Effect of ultra low doses of histamine on human basophil degranulation triggered by anti-IgE Sainte-Laudy, J.Belon, P.

112

V CLINICAL PHARMACOLOGY A study of the effectiveness of ultra low doses of copper in the treatment of hemodialysis-related muscle cramps Hariveau, E.Nolen, P.Holtzscherer, A.

118

Action of aspirin after ingestion at ultra low doses in healthy volunteers Lalanne, M.C.De Seze, O.Le Roy, D.Doutremepuich, C.Boiron, J.

122

Index

129

Preface

Research on Ultra Low Doses (ULD) is a multidisciplinary concept, situated at the crossroads of medical, human, biological and physical sciences. Determination of the mechanism of action is at present being widely developed, with numerous physico-chemical findings. Many questions about ULD efficacy now have a proven answer. However, other questions have arisen for which there are not enough experimental findings to provide definite conclusions. It is therefore of interest to convene an assembly of all people working in this field, to compare their results and conclusions. Fifteen countries were represented in Bordeaux in September 1990, for the first ‘International Congress on Ultra Low Doses’. The proceedings of these communications are summarized in this issue. The scientific committee was professors Aran (INSERM, France), Bonavida (USA), Dufourcq (CNRS, France), Roberfroid (Belgium) and Turner (GB). The editors wish to thank the authors for their contribution. They are also indebted to M.Claire Lalanne, for supporting the copy preparation. They hope that these proceedings may serve as a source of material for all investigators, researchers and students, who will be attracted by this highly interesting area. The kind cooperation and help from the publisher, Taylor & Francis, is hereby acknowledged. Professor C.Doutremepuich

I EXPERIMENTAL PHARMACOLOGY

FIRST EXPERIMENTAL ARGUMENTS IN FAVOR OF THE EFFECT OF VERY WEAK DOSES OF COPPER ON DIGESTIVE MOTRICITY IN MICE AND RABBITS Santini R.*, Tessier M.**, Belon P.*** and Pacheco H.* * INSA 20 Avenue Albert Einstein, 69621 Villeurbanne, France ** 136 Avenue Thiers, 69006 Lyon, France *** Institut BOIRON, 69110 Sainte Foy-Lès-Lyon, France INTRODUCTION During a general program of evaluation of homeopathic treatments in experimental pathology, it was pointed out that preliminary treatment with Cuprum 4 CH inhibited the facilitating effects of Neostigmine, a parasympathomimetic substance, on intestinal transit in mice and rabbits. Cuprum 4 CH (fourth centesimal dilution) is an homeopathic pharmaceutical preparation composed of a metal base of pure copper, made according to the Hahnemannian method of preparation described in the French pharmacopoeia, and corresponding to a molar solution of about 10−10. FIRST STUDY DESIGN—INTESTINAL TRANSIT IN MICE METHODS AND MATERIALS Intestinal transit was studied in mice using a technique derived from that of LOEWE. The transit marker used was phenol-sulfonephtalein or P.S.P., administered to healthy mice “per os” at T=0, in volumes of 0.3 ml. At T=+10 min. the mice were decapitated and the P.S.P. migratory front was observed by applying 20% sodium (NaOH) to the intestin (from the the presence of P.S.P. The percentage of P.S.P. migration was calculated for each mouse by measuring the length of the small intestin and by measuring the marker’s intestinal movement from the pylorus. Two experiments were carried out: In the first experiment 36 OF1 adult male mice, who had not been fed for 24 hours, were randomly separated into 3 groups:

FIRST EXPERIMENTAL ARGUMENTS IN FAVOR 3

Group 1: Intestinal transit comparison or reference group which was given a placebo treatment of distilled water: 0.3 ml., intraperitoneally (I.P.), at T=−24 hrs. and T=−5 hrs., 0.1 ml. was given at T=−10 min. Group 2: Neostigmine group, given 0.3 ml. of distilled water, I.P. at T=−24 hrs. and T=−5 hrs.; and 50 µg/kg of Neostigmine I.P. at T=−10 min. Group 3: Neostigmine+Cuprum group, given 0.3 ml. I.P. of Cuprum 4 CH at T=−24 hrs. and T=−5 hrs, and 50 µg/kg I.P. at T =−10 min. In the second experiment 48 O.F.A. adult female mice, who had not been fed for 24 hours, were randomly separated into 4 groups: 3 groups which were identical to the first experiment; and a fourth group: the Cuprum group, given 0.3 ml. I.P. of Cuprum 4 CH at T=−24 hrs. and T=−5 hrs.; and 0.1 ml. of distilled water at T=−10 min. Statistical analysis was carried out on migration percentages for each mouse of each group, using the Kruskall-Wallis non-parametric rank test. RESULTS The results are indicated in the following tables: Table 1. Intestinal transit in mice. First experiment. Results. Group

Mean migration percentages (M±sm)

Group 1=reference 40.66±4.67 Group 2=Neostigmine 74.91±6.52 51.76±7.35 Group 3=Cuprum+Neostigmine Statistics on 48 values (Kruskall-Wallis) Group 2 different from Group 1 (p