Cytotoxicity of weak electrolytes after the adaptation of cells to low pH: role of the transmembrane pH gradient

Theory suggests that the transmembrane pH gradient may be a major determinant of the distribution of lipophilic weak electrolytes across the cell membrane. The present study evaluates the extent to which this factor contributes to pH-dependent changes in the cytotoxicity of two such chemotherapeutic drugs: chlorambucil and mitoxantrone. Experiments were performed with two cell types of the same origin but exhibiting different pH gradients at the same extracellular pH (pHe): CHO cells cultured under normal physiological conditions (pH 7.4) and acid-adapted cells obtained by culturing under low pH conditions (6.8). Over the pHe range examined (6.0-7.6), the difference between intracellular pH (pHi) and pHe increased with decreasing pHe. Acid-adapted cells were more resistant to acute changes in pHi than normal cells, resulting in substantially larger gradients in these cells. Drug cell survival curves were performed at pHe values of 6.4, 6.8 and 7.4. The cytotoxicity of chlorambucil, a weak acid, increased with decreasing pHe, and low pH-adapted cells were more sensitive than normal cells at the same pHe. In contrast, for the weak base, mitoxantrone, cytotoxicity increased with pHe and was more pronounced in normal cells. As predicted by the theory, the cytotoxicity of both drugs changed exponentially as a function of the pH gradient, regardless of cell type. For mitoxantrone, the rate of such change in cytotoxicity with the gradient was approximately two times greater than for chlorambucil. This difference is probably due to the presence of two equally ionizable crucial groups on mitoxantrone vs one group on chlorambucil. It is concluded that the cellular pH gradient plays a major role in the pH-dependent modulation of cytotoxicity in these weak electrolytes. The data obtained also suggest that a pronounced differential cytotoxicity may be expected in vivo in tumour vs normal tissue. In comparison with normal cells at a pHe of 7.4 (a model of cells in normal tissues), acid-adapted cells at a pHe of 6.8 (a model of cells distal from supplying blood vessels in tumours) were more sensitive to chlorambucil, with a dose-modifying factor of approximately 6, and were more resistant to mitoxantrone by a factor of 14.     

Geographical informational technology as the basis for the informational integration for the large-scale evaluation of the environment

Complex evaluation of environmental state requires processing of extensive information describing various components and objects of environment. Characteristic of this information is territory fix--each environmental object has definite geographic position and border. The authors discuss effects of up-to-date geographic information technologies on evaluation of environmental state in Bashkortostan Republic. Examples of analysis and simulation of possible changes in environmental state are given.     

Transurethral endoscopic electrovaporization in the treatment of patients with benign prostatic hyperplasia

The adenoid tissue is an immunecompetent lymphoid organ, which has the capacity of reacting against numerous antigens. We have studied the influence that the elimination of the said tissue would have on the total IgE serum levels in 33 patients of an average age of 5 and criteria of adenoidectomy and in whom these levels were measured before and after surgery. We have not noticed any statistically significant differences in the IgE values after adenoidectomy with respect to those prior to surgery, which were normal. Adenoidectomy, like other authors have observed after tonsillectomy, does not alter the IgE serum values.     

Natural occurrence of Fusarium toxins in feedstuff

The mycotoxins diacetoxyscirpenol, deoxynivalenol, and zearalenone, produced by Fusarium roseum, were found naturally occuring in mixed feed samples. In all cases analyzed, deoxynivalenol occurred together with zearalenone. The natural occurrence of zearalenone in sesame seed is reported for the first time. Strains of F. roseum isolated in various parts of the world form feed implicated in animal mycotoxicosis produced monoacetoxyscirpenol, diacetoxyscirpenol, deoxynivalenol, and zearalenone.     

Cardiovascular risk reduction in a community setting: some comments

Four case reports are presented of patients who ate the meat of a hog inadvertently fed seed treated with fungicides containing ethyl mercury chloride. The clinical, electrophysiological, and toxicological, and in two of the patients the pathological data, showed that this organic mercury compound has a very high toxicity not only for the brain, but also for the spinal motoneurones, peripheral nerves, skeletal muscles, and myocardium.