Longer-term effects

PTH is the most important regulator of bone remodelling and calcium homeostasis. PTH is an 84-amino acid polypeptide and is secreted by the parathyroid glands in response to reductions in blood levels of ionised calcium. The primary physiological effect of PTH is to increase serum calcium. To this aim, PTH acts on the kidney to decrease urine calcium, increase mine phosphate, and increase the conversion of 25-OH-vitamin D to l,25-(OH)2-vitamin D. PTH acts on bone acutely to increase bone resorption and thus release skeletal calcium into the circulation. However, due to the coupling of bone resorption and bone formation, the longer-term effect of increased PTH secretion is to increase both bone resorption and bone formation. 

Repeated dose chronic toxicity studies are performed on two species of animals a rodent and nonrodent. The aim is to evaluate the longer-term effects of the drug in animals. Plasma drug concentrations are measured and pharmacokinetics analyses are performed. Vital functions are studied for cardiovascular, respiratory, and nervous systems. Animals are retained at the end of the study to check toxicity recovery. Table 5.2 shows the duration of the animal studies, which depends on the duration of the intended human clinical trial. Appendix 6 summarizes the information to be submitted to regulatory authorities. 

Jensen P. Longer term effects of stimulant treatments for attention-deficit/hyperactivity disorder. J Attention Disord 2002 6(Supplement 1) S17-S30. 

Fairburn, C., Jones, R., Peveler, R., and Hope R. (1993) Psychotherapy and bulimia nervosa longer-term effects of interpersonal therapy, behavior therapy and cognitive behavioral therapy. Arch Gen Psychiatry 50 419 28. 

In addition to the acute intoxicating effects and the chronic reverse tolerance effects of cocaine, all of which are mediated by increasing dopamine levels due to its release from dopamine synapses, there are also longer-term effects of cocaine, possibly due to other, more traditional desensitization types of adaptations of dopamine receptors. As abusers use cocaine for longer and longer periods of time, their dopamine receptors become desensitized (down-regulated) as they adapt to chronic... 

All the technological solutions mentioned already have in common that the problem to be solved was defined too narrowly in space, time, and lifecycle phases. Wider-ranging and longer-term effects on the local and global scales on humans, nature, and ecology were not taken into account. 

Cumulative (Longer Term) Effects of Repeated Exposure to Surfactants... 412... 

The postsynaptic transduction of the dopamine signal, whether steady-state, pulse increase, or the pulse decrease in concentration, depends on the relative predominance of Dl-like or D2-like dopamine receptors in the postsynaptic cell. The steady-state levels appear to be sufficient to activate both subtypes of receptor, as locally applied antagonists of either receptor subtype produce physiological effects. Two broad classes of postsynaptic effects can be identified immediate, short-term effects which reverse rapidly, and longer-term effects which persist after the removal of the dopamine signal. 

In addition to the acute toxic effects on the eyes, skin, and respiratory tract, both acute and longer-term neuropsychiatric effects (e.g. depression, anxiety, neurasthenia, insomnia, post-traumatic stress syndrome) have been documented for individuals exposed to sulfur mustard (Romano et al, 2008). Many of these effects have been documented for individuals exposed during noncombat (e.g. munitions plant workers) activities and are not always the result of high-level exposure that result in serious overt effects. Longer-term effects such as chronic bronchitis have been associated with occupational exposures that included episodes of acute toxicity, and delayed or recurrent keratitis may occur 8-40 years after a severe vapor exposure. Sulfur mustard-induced immunosuppression resulting in greater susceptibility to infections has also been reported. 

Of the large number of radioisotopes produced in a nuclear explosion, most are either present in small amounts or decay quickly. A small number of long-half-life radioisotopes could have a potential longer-term effect on human health (e.g. those towards the bottom of Table 8.4). 

The longer-term effects of immunosuppression, and in particular the residual hematological and immunological abnormalities in patients with aplastic anemia treated with antilymphocjde globulin, have been documented there is toxicity to hemopoietic cells, eventually leading to clonal marrow diseases years after treatment (37). Paroxysmal nocturnal hemoglobinuria, refractory sideroblastic anemia, chronic myelomonocytic leukemia, or acute leukemia can develop 4-10 years after treatment (40). 

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