[History of "special therapeutic directions": the example of homeopathy]. / Geschichte der "besonderen Therapierichtungen": Beispiel Homöopathie.

As for generally accepted therapeutic methods, the "special methods" may appear to be effective due to spontaneous recovery provided by nature. A great number of sceptical physicians are aware of this fact. The pharmacologist works continuously to differentiate effects directly caused by medical treatments - mainly drugs - from effects resulting from spontaneous recovery. This is one of the most difficult problems in medical treatment. As a representative example of all "special methods", we concentrate here on the history of homeopathy. As is generally known, there is no conformity in homeopathy, for example monotherapy versus therapy with complex homeopathic products; refusing the simile-rule; treatment with high potencies versus treatment with low potencies; classic versus scholastic homeopathy. The number of homeopathies really equals the number of homeopathic physicians. For this reason, instruction in homeopathy on the academic level is impossible. In addition, we have to forget all natural laws only to prove that "potentiation" may be true. Therapeutic success due purely to chance may be explained rationally and is occasionally seen in all other "special methods". The theories of homeopaths for the action with homeopathic products are neither in accordance with our natural laws nor comply with a rational philosophy.

[Is homeopathy a false doctrine?]. / Homöopathie eine Irrlehre?

We realize that it is virtually impossible to persuade the convinced practitioners of any of the pseudo-scientific beliefs. Therefore, it is our aim to support those fellow workers and interested laymen, intimidated by the contentions of homeopaths by providing them with relevant facts to counter the mostly absurd claims put forward by practitioners of alternative medicine. 1. The rule of "similarity" is based on incorrect assumptions. 2. Dilution = Dilution A dilution is neither a "potentization" nor a "dynamization" nor an "energyzation". All these expressions are not based on carefully defined notions or concepts but are merely literal creations of homeopaths. It is well known that the "Urtinktur" in addition to producing desired effects possesses a substantial number of undesired side effects. The reader might wonder why only the beneficial effects would be amplified ("potentiated") while all other side effects would happen to be attenuated ("diluted"). 3. The only evidence all practitioners of pseudo-medicine can muster to prove the efficacy of their methods are occasional healings following pseudo-medical treatment.

Interaction of obidoxime with sarin in aqueous solution.

The interaction of obidoxime (Toxogonin) with sarin was shown by different analytical methods. The UV spectrum of obidoxime at pH 7.4 yields two absorption maxima, lambda 1 = 284 nm and lambda 2 = 353 nm. The peak at lambda 2 = 353 nm is representative for the amount of zwitter-ionic obidoxime, i.e. the active form of obidoxime. By addition of sarin, lambda 1 shifts immediately to 278 nm and the intensity at lambda 2 decreases, thus indicating an interaction. TLC and 31P-NMR evidence shows that both mono-phosphonylated and diphosphonylated obidoximes are present. Decomposition of phosphonylated obidoxime in MOPS (3-[N-morpholino] propanesulfonic acid) buffered D2O at pH 7.4 occurs with t1/2 = 13.3 min at 24 degrees C. Decomposition of di-phosphonylated obidoxime is faster. It is suggested that decomposition of di-phosphonylated obidoxime occurs through the mono-phosphonylated form. Formation and decomposition of mono- and di-phosphonylated obidoxime is pH dependent. We conclude that obidoxime exerts a detoxifying effect by capturing free sarin molecules and thus increasing its polarity. Thereby the transition of sarin through the blood-brain barrier is restricted and its renal elimination facilitated.

[Homeopathy]. / Homöopathie.

Homeopathy has been disputed from the early beginning. The rational basis of homeopathy neither can be established by philosophy nor by natural sciences. On one hand homeopathy is supported by so-called 'empirical physicians', but on the other hand it is usually heavily criticized by physicians who are basing their criticism on natural sciences. 'Healing' is meant to prove the hypothesis of all paramedical people, it can however be easily explained on a rational basis. It is indisputable that paramedical manipulations not only may act by placebo effect but also can appear successful due to the remarkable power of our body for self-healing. If latter plays an important role, especially when there is no time limit for healing. We never tried to convince paramedical ideologists, who are already heavily engaged in paramedical treatment, but it is our aim to reassure with solid arguments colleagues, who have so far been overwhelmed by irrational journalism.

Isolation and purification of acetylcholine receptor proteins by affinity chromatography.

In order to further molecular investigations on the binding capacity of acetylcholine receptors, a method was developed for the affinity chromatography of the nicotinic acetylcholine receptor. Reversibly binding cholinergic ligand groups were used as affinity ligands, instead of the well known snake venom alpha-toxins. These ligands are small in size, chemically well defined and fixed to long spacer chains (at least 40 nm). One ligand, with a pharmacologically stabilizing effect on the receptor, was a derivative of gallamine. Another, with a depolarizing effect, resembled carbamoylcholine and a third was a derivative of decamethonium. The receptor proteins were isolated from Torpedo marmorata electric organs. Preparation included solubilization with a non-ionic detergent, alkaline treatment to extract peripheral membrane proteins and affinity purification. The receptor proteins eluted from the three affinity resins were identical in their assembly of subunits (alpha, beta, gamma and delta) but of different purity. Receptor proteins were obtained on a large scale within a short time and under mild conditions for elution with the affinity ligands of the decamethonium or the gallamine type. This was a considerable advantage compared to the use of alpha-bungarotoxin.

[Neomysticism in medicine. The example of homeopathy]. / Der Neomystizismus in der Medizin. Beispiel Homöopathie.

The revival of neomysticism, especially promoted by nonqualified representatives of press and tv, leads to a worldwide trend to homoeopathy, acupuncture, herb-cure, Christian-Science, and to many others. According to the comprehensive publications of Prokop, the successful treatment by paramedical methods are due to placebo and self-healing. The statements of paramedical representatives will be accepted by the public, if representatives of science do not offer adequate criticism. Successful healing by any kind of treatment--e.g. of disturbances of well-being--is well established. Representatives of paramedicine applying "mystical treatment" to humans are obliged with necessity to explain success as "mysticism". In any case it is unwise to use the basis of natural science to explain mystic phenomena, as the representative of paramedicine--and occasionally a "mystic-oriented" representative of natural science--proves his lack of sound judgement.

Sarin poisoning in guinea pigs compared to reactivation of acetylcholinesterase in vitro as a basis for therapy.

Contrary to the large number of publications dealing with treatment of organophosphate poisoning in a variety of animal species, there is no logic reason in the preference of one species, for this purpose. Guinea pigs were reported to respond better to treatment by oximes, than mice and rats. However, in the analysis of data on the effect of obidoxim and atropine or benactyzine on sarin poisoning it is demonstrated, that guinea pigs do not respond differently from mice and rats. Subcutaneous LD50's of sarin in mice ranged from 0.06 to 0.207 mg/kg, and those of guinea pigs from 0.04 to 0.112 mg/kg. The difference in the LD50's may be related to the different susceptibility of various animal species. The importance of "in vivo" dosage, mode of application, kinetics of antagonists, in correlation to the ability to reactivate "in vitro" is discussed.

Activation of acetylcholinesterase by monovalent (Na+,K+) and divalent (Ca2+,Mg2+) cations.

The activation of acetylcholinesterase [EC 3.1.1.7 (AChE)] by monovalent and divalent metal ions has been investigated by kinetic experiments under steady-state conditions (pH-stat method). It has been shown that at low ionic strength the enhancement of the activity by both monovalent and divalent metal ions can be explained as an electrostatic effect. Thereby, enhancement of the concentration of monovalent metal ions (Na+ and K+) acts by reducing the penetration depth of the electric field of carboxylate groups located at the active center whereby divalent metal ions (Ca2+ and Mg2+) act by a complex formation with these charged groups.

Blockade of acetylcholine synthesis in organophosphate poisoning.

In spite of worldwide research efforts in the search for the treatment of organophosphate poisoning, the substances with practical antidotal capabilities remain to be discovered. This problem has generally been approached by attempting to reactivate the inhibited acetylcholinesterase. Our approach consisted of reducing the amount of the lethal agent acetylcholine by blocking its synthesizing enzyme cholineacetylase with methyl methane thiol sulfonate (MMTS). We have taken into consideration that we are dealing with acute toxicological problems. This applies for poisoning as well as for treatment, and therefore in the present stage we can only present minimal results. The time from sarin (2 mg/kg) injection to death in rats (controls) was 2:59 min. With a MMTS dosage of 133.5 mg/kg prior to sarin, it was prolonged to 20:55 min (p less than 0.01). With the same dosage of MMTS under identical conditions, the time from soman (2 mg/kg) injection to death was prolonged from 6:08 to 14:48 min (p less than 0.01). Although MMTS cannot be used as a therapeutic agent, our attempt has demonstrated a utility in treating organophosphate poisoning in mice and rats and points in a direction where further work might be fruitful.

Affinity chromatography of cholinergic receptor proteins.

Cholinergic binding proteins were purified from torpedo electric organ. The preparation comprises: solubilization by non-ionic detergents followed by unspecific prepurification. For prepurification the double reversed technique proved to be very useful. Finally we applied affinity chromatography. For the affinity purification we used resins with chemically well defined small ligand groups from the depolarizing type (carbachol- and decamethonium-analogue), and from the stabilizing type (gallamine amide amine). The purified receptor proteins from all three resins showed different subunit compositions and different properties of alpha-bungarotoxin binding.