In this review, we focus on the medicinal drugs from humus matter such as peat, sapropel, and mumie. The most clinically available medicines, containing peat and sapropel extracts, are Torfot, Tolpa Peat Preparation (TPP), Peloidodistillate, Humisol, Peloidin, FiBS, and Eplir. Much attention in the review is concentrated on mumie composition, its pharmacological properties, and new pharmacological drugs with mumie (Shilagen, Abana, Cystone, Diabecon 400, EveCare, Geriforte, Lukol, Pilex, Rumalava, Tentex forte, Nefrotec, Adrenotone, Siotone, La-Tone Gold, Andro-Surge, Solanova Libidoplex). It was concluded that therapeutic properties of crude extracts from peat, sapropel, and mumie have similarity to the ones of fulvic and humic acids. They are antibacterial, antitoxic, antiradical, antiulcerogenic, antiarthritic, immunomodulatory, and antiinflammatory properties. Possible directions for better development of new drugs from humus matter are discussed. Drug Dev. Res. 57:140–159, 2002. © 2002 Wiley-Liss, Inc.

Medical drugs from humus matter: Focus on mumie

Aspirin and immune system.

In accordance with the present invention, there are provided in vivo methods for the reduction of cyanide levels. The present invention employs a scavenging approach whereby cyanide is bound in vivo to a suitable scavenger. The resulting complex renders the cyanide harmless, and is eventually excreted in the urine of the host. Further in accordance with the present invention, there are provided compositions and formulations useful for carrying out the above-described methods.

Methods for in vivo reduction of nitric oxide levels and compositions useful therefor

Susceptibility to infections, autoimmune disorders and tumor progression is strongly influenced by the activity of the endocrine and nervous systems in response to a stressful stimulus. When the adaptive system is switched on and off efficiently, the body is able to recover from the stress imposed. However, when the system is activated repeatedly or the activity is sustained, as during chronic or excessive stress, an allostatic load is generated, which can lead to disease over long periods of time. We investigated the effects of chronic cold stress in BALB/c mice (4°C/4 h daily for 7 days) on functions of macrophages. We found that chronic cold stress induced a regulatory phenotype in macrophages, characterized by diminished phagocytic ability, decreased TNF-α and IL-6 and increased IL-10 production. In addition, resting macrophages from mice exposed to cold stress stimulated spleen cells to produce regulatory cytokines, and an immunosuppressive state that impaired stressed mice to control Trypanosoma cruzi proliferation. These regulatory effects correlated with an increase in macrophage expression of 11β-hydroxysteroid dehydrogenase, an enzyme that converts inactive glucocorticoid into its active form. As stress is a common aspect of modern life and plays a role in the etiology of many diseases, the results of this study are important for improving knowledge regarding the neuro-immune-endocrine interactions that occur during stress and to highlight the role of macrophages in the immunosuppression induced by chronic stress.

Chronic cold stress in mice induces a regulatory phenotype in macrophages: correlation with increased 11β-hydroxysteroid dehydrogenase expression.

Polymorphonuclear leukocytes in ischemic vascular disease

The cold stress induced in rabbits by lowering their body temperature by 3 degrees C resulted in neutrophilia and a decrease in number of phagocytes and phagocytized bacteria. The stress did not affect the number of lymphocytes and the ability of forming E rosettes by T lymphocytes, but depressed the formation of EAC rosettes by B lymphocytes. This inhibition of neutrophil activity was antagonized completely by acetylsalicylic acid, and substantially by mefenamic acid and indomethacin administered, in doses inhibiting pyrogen-induced fever, either 2.5 h before or 1.5 h after the hypothermia. The drugs did not antagonize the depression of the ability of formation of EAC rosettes.

Responses of neutrophils and lymphocytes in the cold stress: effects of nonsteroid anti-inflammatory drugs.

Normothermic rabbits and rabbits with LPS induced fever were treated with chlormethine (Nitrogranulogen, Ntg) in the doses of 1 microgram/kg and 10 micrograms/kg. The blood was collected 4, 24, 48 hrs and 4, 7, 10 days after Ntg injection. Following indices of immunity were studied: T and B cells number, number of IgM producing cells after immunization with SRBC, serum IgG level, killing activity of neutrophils and number of phagocytized bacteria. It was observed that both doses of Ntg injected intravenously to normothermic rabbits, significantly increased the number of T and B lymphocytes and of IgM producing lymphocytes a well as the level of IgG in the serum, number of phagocytized bacteria and killing activity of neutrophils. Ntg in combination with LPS shortened the period of fever, and through the synergistic effect, significantly increased T lymphocytes number in the blood, IgG level in the serum, number of phagocytized bacteria and killing activity of neutrophils.

Chlormethine in small doses as immunostimulator--LPS synergism.

The experiments were carried out on normothermal rabbits and rabbits exposed to cold stress (hypothermia). The animals of the latter group were submerged in ice-water for 20 s and then placed in a freezer at -15 degrees C for 8 min until their body temperature dropped by 3 degrees C. Both the normothermal and hypothermal rabbits were immunized i.p. with 3 ml of 10% sheep red blood cells (SRBC). Levamisole (2 mg/kg), DTC (sodium diethyldithiocarbamate, 20 mg/kg) or mechlorethamine (mustine; 5 micrograms/kg) were injected i.v. three times at 24-h intervals. The number of PFC, total (19S + 7S) and 2-mercapthoethanol resistant (7S) serum haemagglutination titres were determined. It was found that, in normothermal rabbits, all three agents potentiated the number of plaque-forming cells (PFC); the impact of DTC was the strongest, while the weakest influence was observed for mechlorethamine. Furthermore, DTC increased anti-SRBC haemagglutinin titre, whereas mechlorethamine did not. Levamisole, on the other hand, reduced total serum haemagglutinin titre. Cold stress reduced humoral response to SRBC, which was reflected in the decreased number of PFC and serum haemagglutination titres (19S + 7S and 7S). Each agent showed a different way of action. Pretreatment with DTC prevented the immunosuppression caused by cold stress, while levamisole and mechlorethamine only reduced the immunosuppressive effect.

Effects of Levamisole, DTC and Low‐dose Mechlorethamine on Humoral Response of SRBC‐immunized Rabbits Exposed to Cold Stress

Tolpa Peat Preparation (TPP) was administered to mice in daily doses of 1, 10 and 50 mg.kg-1 for 3, 5, 7, 9 or 12 consecutive weeks. After each of the above mentioned periods the primary response to sheep erythrocytes (SRBC) was examined by determination of the percentage of splenocytes forming E rosettes, the number of splenocytes producing anti-SRBC haemolysins of 19S and 7S type, and the level of serum haemagglutinins to SRBC (19S + 7S and 7S types). The effect of enhanced humoral response by TPP was observed in mice immunized with SRBC. This effect depended, first of all on TPP does but also on the duration of time TPP administration. The stimulating effect on the humoral response occurred after the daily dose of 1 mg.kg-1 during 12 weeks. On the other hand, the daily doses of 10 or 50 times higher enhanced the humoral response only during the first 5-7 weeks of TPP administration. Longer administration of TPP in these doses caused disappearance of this effect or reduction of the response to SRBC.

The influence of long-term administration of Tołpa Peat Preparation on immune reactivity in mice. III. The effect on primary humoral response to sheep erythrocytes.

The effect of the following doses of mechloretamine: 1, 5, 10, 25, 50, 100, 250 and 500 μg/kg on the immunological response in mice immunized with sheep red blood cells (SRBC) was investigated. the number of plaque forming cells (PFC) to SRBC, the serum hemagglutinins level and the number of lymphocytes forming E or EAC-rosettes were determined. Depending on mechloretamine dose the following effects on the tested parameters were obtained : (i) only stimulating -1 and 5 pg/kg, (ii) stimulating or suppressive according to the test -10–100 pg/kg, (iii) only suppressive -250 and 500 μg/kg. Mechloretamine (5 μg/kg) induced the increase in PFC in comparison with levamisole (2 mg/kg). the difference between the action of mechloretamine and levamisole used in immunostimulating doses on the increased anti-SKBC antibodies or on the E-rosette forming lymphocytes was revealed.

The dose-dependent influence of mechloretamine on the response to sheep erythrocytes in mice. Comparison of immunostimulating properties of mechloretamine with levamisole.

Debowy J

Papers

Responses of neutrophils and lymphocytes in the cold stress: effects of nonsteroid anti-inflammatory drugs.

Chlormethine in small doses as immunostimulator--LPS synergism.

Effects of Levamisole, DTC and Low‐dose Mechlorethamine on Humoral Response of SRBC‐immunized Rabbits Exposed to Cold Stress

The influence of long-term administration of Tołpa Peat Preparation on immune reactivity in mice. III. The effect on primary humoral response to sheep erythrocytes.

The dose-dependent influence of mechloretamine on the response to sheep erythrocytes in mice. Comparison of immunostimulating properties of mechloretamine with levamisole.