The "second disease" and "second nature"

An idea about the second disease as a metamorphosis when the phenomenon of one nature is transformed into phenomenon of the second nature is proposed. There are three stages in the development of the second disease: origin, when clinical and morphological features of initial and new nosologic forms coexist; formation-distinct groups of features of a new nosologic form which preserved a link to the first disease; separation of this new nosologic form with its typical clinical and morphological features. The second disease is metamorphosis of the first disease which develops into a new nosologic entity under the influence of exogenous or endogenous factors.     

Motoneurones "learn" and "forget" physical activity.

In spite of our knowledge of activity related adaptations in supraspinal neurones and skeletal muscles, very little is known concerning adaptations in alpha-motoneurones to alterations in chronic activity levels. Recent evidence shows that the biophysical properties of alpha-motoneurones are plastic and adapt to both increases and decreases in chronic activation. The nature of the adaptations--in resting membrane potential, spike threshold, afterhyper-polarization amplitude,and rate of depolarization during spike generation--point to involvement of density, type, location, and/or metabolic modulation of ion conductance channels in the motoneuronal membrane. These changes will have significant effects on how motoneurones respond when activated during the generation of movements, and on the effort required to sustain activation during prolonged exercise. Since the adaptations most likely involve structural changes in the motoneurones and changes in protein synthesis, and change the output response of the cells to input, they are considered to be learning responses. Future research directions for examining this issue are outlined.     

Physiological response patterns during "intake" and "rejection" tasks

Two 2-min tasks, one requiring outer-directed attention (intake task), the other a mental arithmetic task (rejection task) were presented to 20 subjects. According to Lacey the distinguishing feature of the response to intake tasks are cardiac deceleration and blood pressure decreases. None of these responses was obtained. Some variables, however, were only affected by one of the tasks; the intake task led to a decreased hand (skin) blood flow and an increased hand vascular resistance, whereas a heart rate acceleration and increased forearm (muscle) blood flow and decreased forearm vascular resistance were observed during the rejection task. Blood pressure, respiration rate and skin conductance were similarly affected by the two tasks. Inconsistencies among previous studies of the response to the two types of tasks were discussed and found to be partially explained by methodological differences.     

Bone "mass" and the "mechanostat": a proposal

The observed fit of bone mass to a healthy animal's typical mechanical usage indicates some mechanism or mechanisms monitor that usage and control the three longitudinal growth, bone modeling, and BMU-based remodeling activities that directly determine bone mass. That mechanism could be named a mechanostat. Accumulated evidence suggests it includes the bone itself, plus mechanisms that transform its mechanical usage into appropriate signals, plus other mechanisms that detect those signals and then direct the above three biologic activities. In vivo studies have shown that bone strains in or above the 1500-3000 microstrain range cause bone modelling to increase cortical bone mass, while strains below the 100-300 microstrain range release BMU-based remodeling which then removes existing cortical-endosteal and trabecular bone. That arrangement provides a dual system in which bone modeling would adapt bone mass to gross overloading, while BMU-based remodeling would adapt bone mass to gross underloading, and the above strain ranges would be the approximate "setpoints" of those responses. The anatomical distribution of those mechanical usage effects are well known. If circulating agents or disease changed the effective setpoints of those responses their bone mass effects should copy the anatomical distribution of the mechanical usage effects. That seems to be the case for many agents and diseases, and several examples are discussed, including postmenopausal osteoporosis, fluoride effects, bone loss in orbit, and osteogenesis imperfecta. The mechanostat proposal is a seminal idea which fits diverse evidence but it requires critique and experimental study.