17 beta-estradiol for postmenopausal estrogen replacement therapy.

After physiological or surgical menopause, women are suddenly deficient in their main estrogenic hormone, 17 beta-estradiol. Only a very small amount of estradiol is still produced from adrenal precursors. More than 50 per cent of all postmenopausal women suffer for varying periods of time from the symptoms of this estrogen deficiency, most notably vasomotor instability (hot flashes) and sleep disturbances. The trophic symptoms of estrogen deficiency have longer lasting and cumulative consequences: accelerated loss of bone density that eventually increases the risk of fractures, genitourinary atrophy resulting in dyspareunia and urinary atrophy; and lipoprotein changes with increased risk of coronary heart morbidity and mortality. Today estrogen deficiency is mainly treated by oral estrogens--either conjugated equine estrogens or estradiol--in milligram doses far in excess of what would be required by the parenteral route. Taken orally, estradiol is largely transformed to estrone through metabolism in the liver. Certain undesirable side effects of estrogen therapy (e.g., increased renin substrate) are caused by the unphysiologic nature of the oral route of administration. Dosage forms for parenteral estrogen administration have been widely studied: vaginal or percutaneous creams, intranasal solutions, and sublingual tablets. All of these result in a pronounced, transient elevation of plasma concentrations of estradiol and a minor increase of estrone. An improved regimen, which produces more constant plasma concentrations, is achieved with an experimental estradiol implant or with a vaginal ring delivering estradiol. These studies demonstrate that daily estradiol doses of 0.2 mg and less are effective in reducing hot flashes. Effective doses of conjugated estrogens and estradiol administered by different routes achieve estradiol plasma concentrations of similar magnitude (between 35 and 100 pg/ml). Estrone plasma levels vary widely with these different regimens and do not seem to be directly related to efficacy. In summary, the literature indicates that efficacy of estrogen replacement for the treatment of the menopausal symptoms appears to relate to the magnitude of estradiol plasma levels; effective therapy is achieved by an estradiol regimen that maintains plasma estradiol levels of at least 35-55 pg/ml. Efficacy of estrogens in the prevention of osteoporosis as assessed by densitometry has been demonstrated for conjugated oral estrogens.(ABSTRACT TRUNCATED AT 400 WORDS)

The postnatal development of the inferior oblique muscle of the cat. III. Fiber sizes and histochemical properties.

Transversal sections of the inferior oblique muscle from kittens of various ages and from adult cats were stained for myofibrillar ATP-ase at Ph 9.4 and 4.35, succinic dehydrogenase (SDH) and fat. The same muscles had previously been submitted to studies of contractional and fatigue properties. With ATPase the fibers could be differentiated into types I, II and II C. The percentages of each fiber type remained approximately the same from birth onwards. In the inner, global layer of the muscle, type I fibers showed a linear increase in size, but types II and IIC fibers an accelerated growth after age 20 weeks. In the outer, orbital layer, where no type I fibers were seen, type II and II C fibers showed the same growth pattern as in the global layer. The fiber content of SHD and fat was low at birth but increased after two weeks of age. Type I fibers were poor and type II C fibers rich in SDH and fat. Type II fibers showed varying amounts of these substances. Provided that type I fibers are slow, type II fast and type II C intermediate in speed of contraction, like in other muscles, the findings on fiber growth and SDH content seem to support the idea that slow, fatigue resistant components in eye muscles reach maturity earlier than fast components.

Morphology of motor units in cat extraocular nodule.

Muscle fibers from single motor units in cat inferior oblique were marked iontophoretically with procion red injected through an intracellular pipette. The fibers were isolated by dissection and characterized by electron microscopy. A fiber in a slow motor unit with non-conducted electrical responses showed slow fiber morphology of the amphibia-type. Fast, twitch motor units contained fibers with twitch fiber morphology. Thus, a good correlation between muscle fiber structure and function was obtained in these eye motor units, examined with both physiological and morphological techniques.