THYROID DYSFUNCTION FOLLOWING ALPHA-INTERFERON TREATMENT FOR CHRONIC HEPATITIS C

In order to evaluate the influnces of IFNα on thyroid function, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4, tri-iodothyronine (T3), and thyroxine-binding globulin were examined in IFNα-treated 351 patients with chronic hepatitis C before and during therapy. As therapy, either 3 million units (MU) of human lymphoblastoid IFNα or 9MU of recombinant IFNα2a was administrated daily for the initial two weeks followed by three times a week for 22 weeks. There were nine patients showing thyroid dysfunction during IFNα therapy. They consist of one relapse of Graves' disease, one relapse of Hashimoto thyroiditis, one development of apparent thyroid insufficiency from subclinical hypothyroidism, five cases with transient hyperthyroidism and one case with transient hypothyroidism. T4 and T3 levels in most patients who transiently developed thyroid dysfunction were normalized spontaneously after the discontinuation of IFNα. Thyroid-related autoantibodies were positive in 4 patients before IFNα therapy and newly developed in one patient during therapy. Attention should be paid first to the previous histories of autoimmune thyroid diseases and the existence of thyroid-related autoantibodies for the prediction of development of thyroid dysfunction during IFNα therapy. In addition, serial examinations of TSH, T3 and T4 should be also necessary for early detection of transient thyroid dysfunction during IFNα therapy

Ling’s Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling’s adsorption theory was the most plausible theory. Ling’s adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling’s adsorption theory which has for long years been forgotten in the history of physiology

Membrane Potential Generated by Ion Adsorption

It has been widely acknowledged that the Goldman-Hodgkin-Katz (GHK) equation fully explains membrane potential behavior. The fundamental facet of the GHK equation lies in its consideration of permeability of membrane to ions, when the membrane serves as a separator for separating two electrolytic solutions. The GHK equation describes that: variation of membrane permeability to ion in accordance with ion species results in the variation of the membrane potential. However, nonzero potential was observed even across the impermeable membrane (or separator) separating two electrolytic solutions. It gave rise to a question concerning the validity of the GHK equation for explaining the membrane potential generation. In this work, an alternative theory was proposed. It is the adsorption theory. The adsorption theory attributes the membrane potential generation to the ion adsorption onto the membrane (or separator) surface not to the ion passage through the membrane (or separator). The computationally obtained potential behavior based on the adsorption theory was in good agreement with the experimentally observed potential whether the membrane (or separator) was permeable to ions or not. It was strongly speculated that the membrane potential origin could lie primarily in the ion adsorption on the membrane (or separator) rather than the membrane permeability to ions. It might be necessary to reconsider the origin of membrane potential which has been so far believed explicable by the GHK equation

The membrane potential arising from the adsorption of ions at the biological interface

Membrane theory makes it possible to compute the membrane potential of living cells accurately. The principle is that the plasma membrane is selectively permeable to ions and that its permeability to mobile ions determines the characteristics of the membrane potential. However, an artificial experimental cell system with an impermeable membrane can exhibit a nonzero membrane potential, and its characteristics are consistent with the prediction of the Goldman–Hodgkin–Katz eq., which is a noteworthy concept of membrane theory, despite the membrane’s impermeability to mobile ions. We noticed this troublesome facet of the membrane theory. We measured the potentials through permeable and impermeable membranes where we used the broad varieties of membranes. Then we concluded that the membrane potential must be primarily, although not wholly, governed by the ion adsorption-desorption process rather than by the passage of ions across the cell membrane. A theory based on the Association-Induction Hypothesis seems to be a more plausible mechanism for the generation of the membrane potential and to explain this unexpected physiological fact. The Association-Induction Hypothesis states that selective ion permeability of the membrane is not a condition for the generation of the membrane potential in living cells, which contradicts the prediction of the membrane theory. Therefore, the Association-Induction Hypothesis is the actual cause of membrane potential. We continued the theoretical analysis by taking into account the Association-Induction Hypothesis and saw that its universality as a cause of potential generation mechanism. We then concluded that the interfacial charge distribution is one of the fundamental causes of the membrane potential

Revisiting the mechanisms for cellular homeostasis and electrophysiological responses: Classical membrane theory, association-induction hypothesis and murburn concept

Pursuits in modern cellular physiology are fraught with disagreements on the physico-chemical explanations for how a cell coordinates the core aspects of its life-sustaining activities. While the membrane theory of homeostasis deems the cell-membrane and the proteins embedded therein as the chief players, the association-induction (or sorption/bulk-phase) theory deems the protoplasm (the aqueous phase of dissolved proteins) as the key determinant of cellular composition and inflow-efflux of key molecules/ions. In the first school of thought, trans-membrane potential and protein conformations are deemed as key operative principles whereas in the latter theory, sorption-desorption dynamics and re-arrangements of bulk phase determine outcomes. In this exploration/analysis, we first present an unbiased collection of the pertinent founding concepts and viewpoints in the field of cellular homeostatic and responsive mechanisms (that do not invoke genetic-level interventions/regulations). Further, several critical queries are posed that seek us to explore concepts beyond the existing beliefs in homeostatic electrophysiology, for arriving at more holistic solutions. In particular, the discussion focuses on the basic information available on charge/ion differentials of the simple cellular systems and how cells achieve the disparity in the distribution of monovalent and divalent cations, as per the order: K+ > Na+ > Mg2+ > Ca2+. It is suggested that murburn concept (molecule-unbound ion-radical interactions) could be relevant in this quest. Energy metabolism-based outcomes (murburn equilibriums) and the dissolved-phase proteins’ innate ability to bind/adsorb ions selectively are projected as the integral rationale for the observed phenomenon

Ling’s Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling’s adsorption theory was the most plausible theory. Ling’s adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling’s adsorption theory which has for long years been forgotten in the history of physiology

Autonomous oscillatory shape change of DEA induced by the charge–discharge process under a constant voltage

Despite the promising characteristics of Dielectric Elastomel Actuator (DEA) as a practical soft actuator, the need of high voltage for its operation prevents the successful fabrication of a practical DEA, that is, the high voltage generation takes a bulky and costly power supply. Induction of complex shape change motion of DEA such as oscillatory shape change takes even a more bulky and costly multipurpose power supply. It is a serious practical issue to be overcome. In our latest study, however, we could build a simple DEA system which exhibited a relatively complex and autonomous oscillatory shape change merely under a constant voltage, though the voltage needed was high. This successful outcome must broaden the potential usefulness of DEA as a practical soft actuator