Possible role and application of fMRI in the screening of release-active drugs.

Functional magnetic resonance imaging (fMRI) of the brain was applied for preclinical evaluation of the efficiency of Divaza preparation intended for the treatment of cerebrovascular disorders. Psychological testing (Stroop task) in the magnetic field of fMRI was performed before and after 12-week treatment course using a double blind placebo-controlled protocol. It was shown that standard psychological and neuropsychological protocols do not allow fully estimate the results of treatment, whereas fMRI targeted the pool of cerebral structures activated during task solution. In the treatment group (in contrast to placebo), active zones in these structures were found only during task solution. Thus, resolution capability of fMRI significantly extends the range of rational screening by identifying active zones and can radically change the procedure of selection and clinical trials.

Experimental study of the effects of Dietressa, a new weight-reducing drug.

The capacity of a new drug containing ultra-low doses of antibodies to cannabinoid receptor type 1 (Dietressa) to reduce body weight gain in mice on a high-calorie diet was evaluated, possible mechanisms of drug action were analyzed, and its safety (abuse potential in the reaction of self-stimulation) was evaluated. Dietressa was not inferior to sibutramine in reducing body weight gain in mice and exhibited no abuse potential.

Release-activity: a long way from phenomenon to new drugs.

Multiple dilutions of the original substance release its peculiar activity referred to as "release-activity". Although this activity originates from the initial substance, it does not depend on its negligible concentration in extreme dilutions. Thus, the terms "dose", "ultralow dose", and "homeopathic dose", do not correctly describe the release-active solutions, since the concept of dose implies the presence of some part of the original substance in a dilution with its intrinsic therapeutic potency. The data are reported on the molecular and cellular mechanisms of the mode of action of the release-active agents, some of which being introduced into clinical practice.

Experimental study of the efficiency of impaza on the model of chronic aseptic prostatic inflammation.

We compared the efficacy of Impaza (antibodies against endothelial NO-synthase in ultra-low doses) and Serenoa repens on the rat model of chronic aseptic prostatic inflammation. Administration of Serenoa repens in a dose of 50 mg/kg for 1.5 months prevented the development of prostate sclerosis and increased luminal area, but did delay the development of atrophic processes. In animals treated with Impaza (3 ml/kg for 1.5 months), atrophic changes in the prostate gland were practically absent. These findings indicate that Impaza can be used in complex therapy of abacterial prostatitis.

Comparative study of pharmacological activity of afala on the model of hormone-induced prostatitis in rats.

Afala (ultralow-dose antibodies to prostate-specific antigen) injected for 60 days to rats with hormone-induced prostatitis caused by sulpiride prevented the development of prostatic hyperplasia and reduced the severity of histological changes. The effect of Afala was superior to that of the reference drug (Serenoa repens extract).

Improvement of Memory by Means of Ultra-Low Doses of Antibodies to S-100B Antigen.

Antigen S-100B of nervous tissue, according to the data of numerous studies, affects the mechanisms of nervous system plasticity and memory. The influence of ultralow doses of antibodies to S-100B (6C dilution, according to the homeopathic pharmacopoeia) has been studied on three learning behavioral models on Wistar rats, which were inhibitory avoidance, choosing of bowls with sucrose and feeding behavior cessation after auditory signal. For all three tasks, parameters of reproduction of the learned skills improved after per oral administration of potentiated antibodies to S-100B antigen immediately after learning. Possible mechanisms of the anti-S-100B antibodies influence on memory formation are discussed.

Potentiated antibodies to mu-opiate receptors: effect on integrative activity of the brain.

The effect of homeopathically potentiated antibodies to mu-receptors (10(-100) wt %) on integrative activity of rat brain was studied using the models of self-stimulation of the lateral hypothalamus and convulsions produced by electric current. Electric current was delivered through electrodes implanted into the ventromedial hypothalamus. Single treatment with potentiated antibodies to mu-receptors increased the rate of self-stimulation and decreased the threshold of convulsive seizures. Administration of these antibodies for 7 days led to further activation of the positive reinforcement system and decrease in seizure thresholds. Distilled water did not change the rate of self-stimulation and seizure threshold.

Effect of preparations from potentiated ethanol on the content of biogenic monoamines and metabolism of ethanol in tissues of rats during alcoholization.

The effect of homeopathically potentiated ethanol (C30 and C200) on ethanol metabolism was studied in alcoholized rats. We measured ethanol concentration in the blood, alcohol dehydrogenase activity in the liver, and contents of biogenic monoamines in the hypothalamus, septum, and whole blood. Potentiated preparations of ethanol were efficient after long-term treatment and delayed ethanol elimination from the blood. Preparation C200 increased alcohol dehydrogenase activity. Potentiated preparations of ethanol (particularly C200) produced a positive effect on catecholaminergic and serotoninergic systems of the brain, i.e. they enhanced protective and adaptive reactions.

Effect of potentiated antibodies to cyclophosphamide on the development of tumors and effectiveness of cytostatic therapy under experimental conditions.

Antibodies to cyclophosphamide obtained by homeopathic potentiation and administered in ultralow doses exhibit no antiblastic activity and did not modulate the effectiveness of cyclophosphamide during antitumor therapy of animals with transplanted tumors (Lewis lung carcinoma and Ehrlich adenocarcinoma).

Effect of allotransplantation of embryonic brain tissues and administration of potentiated antibodies to bombesin on hemodynamics in rats with emotional hypertension.

Transcutaneous allotransplantation of embryonic tissues from the anterior hypothalamus and amygdaloid complex and administration of potentiated antibodies to bombesin normalized blood pressure and parameters of ECG in rats with emotional hypertension.

Immunotropic effects of potentiated antibodies to human interferon-gamma.

We studied immunotropic properties of antibodies to human interferon-gamma in homeopathic doses. The effects of these antibodies on the ratio between the counts of T helper (CD4+) and T suppressor cells (CD8+), production of interleukin-1 and interleukin-2, and functional activity of natural killer cells were evaluated. Potentiated antibodies slightly decreased the number of CD8+ cells in the spleen of experimental animals. After the addition to cultured human mononuclear cells the preparation produced a moderate comitogenic effect, stimulated proliferation of T and B lymphocytes, increased spontaneous and induced production of interleukin-1, and enhanced functional activity of natural killer cells (under certain conditions).

Antitussive activity of Anar.

Affinity-purified antibodies to morphine (mixture of homeopathic dilutions C30+C200) produced an antitussive effect on male and female guinea pigs with cough induced by citric acid and capsaicin.

Effect of potentiated solutions on mercury(II) signal in inversion voltammetry.

We studied the effects of homeopathically potentiated substances in ultralow doses on physicochemical properties of solutions. Inverse voltammetric signals during Hg(II) oxidation-reduction in the presence of potentiated water, lithium chloride, and mercury nitrate were studied by alternating-current inversion voltammetry. Potentiated substances modified oxidation-reduction processes in the electrochemical system. Potentiated solutions of Hg(II) increased the effective concentration (activity) of mercury ions. The effect was most significant in the presence of mercury nitrate in homeopathic dilutions C6+C12+C24. Our results indicate that potentiated substances specifically modulate kinetic and thermodynamic characteristics of solutions containing the same compounds.

Antibodies to delta sleep-inducing peptide in ultralow doses: study of the effect by enzyme immunoassay.

The effects of potentiated homeopathic preparations containing antibodies to delta sleep-inducing peptide in ultralow doses were studied by enzyme immunoassay. Experiments were performed with the following immunochemical reagents: antigens of delta sleep-inducing peptide conjugated to various macromolecular carriers and specific antigens. Antibodies to delta sleep-inducing peptide were synthesized in dilutions of C3, C6, C12, C50, and C200. Enzyme immunoassay showed that test preparations of antibodies in dilutions of 1:400-1:3200 produce the combined effect on immune complex formation. The proposed method holds much promise for identification of medicinal preparations in ultralow doses.

Potentiated cyclophosphane: experimental study of the effect on tumor development and efficiency of cytostatic therapy.

Experiments on animals with transplanted tumors (Lewis lung carcinoma and carcinosarcoma Walker-256) showed that combination treatment with cyclophosphane and its homeopathically potentiated forms increases antiblastic activity of the preparation.

Potentiated antibodies against morphine: effects on biogenic amines and lipid peroxidation in chronically morphinized rats.

The efficiency of potentiated antibodies against morphine was studied on the model of chronic morphine intoxication. Test antibodies stimulated catecholamine metabolism in the hypothalamus (i.e., prevented initiation of catecholamine- and histaminergic peripheral reactions) and normalized lipid peroxidation.

Potentiated antibodies to tumor necrosis factor-alpha in the therapy of patients with rheumatoid arthritis.

We studied the efficiency and safety of a new homeopathic preparation Artrofoon containing affinely purified antibodies to tumor necrosis factor-alpha in the therapy of patients with rheumatoid arthritis. Artrofoon produced a positive antiinflammatory effect on the course of rheumatoid arthritis. This preparation reduced the severity of arthralgia (indexes of Li and Ritchie) and morning stiffness and decreased the erythrocyte sedimentation rate and contents of rheumatoid factor and C-reactive protein. One-month therapy improved the state of patients. Artrofoon was well tolerable. The preparation did not cause the ulcerogenic and nephrotoxic effects. Artrofoon holds much promise for combination therapy of patients with rheumatoid arthritis (including severe articular-and-visceral forms) and complications after treatment with nonsteroid antiinflammatory preparations.

Use of potentiated preparations to relieve alcohol and opium withdrawal syndromes.

The efficiency of potentiated preparations from ethanol and morphine hydrochloride in the therapy of patients with alcohol and opium withdrawal syndromes was compared in an open clinical trial. Potentiated ethanol relieved the major clinical manifestations, possessed hypnagogic properties, and reduced the severity of neurological and vegetative disorders in patients with the alcohol withdrawal syndrome. Potentiated morphine produced the anxiolytic, myorelaxing, and analgetic effects. Test preparations did not cause side effects.

Use of ANAR for the therapy of opium withdrawal syndrome.

We studied the efficiency of ANAR containing antibodies to morphine (dilutions C300 and C200) in the therapy of patients with the opium withdrawal syndrome. In patients with moderate to severe forms of the opium withdrawal syndrome therapeutic activity of ANAR was comparable to that of standard symptomatic drugs. ANAR possessed vegetostabilizing, sedative, and analgetic properties. Treatment with ANAR allowed us to reduce doses of psychotropic and analgetic preparations and delay the development of withdrawal symptoms by 18-24 h.