The mechanism of the prolonged stimulatory effect of corticotrophin on pregnenolone production by guinea-pig adrenocortical mitochondria

The postulated prolonged stimulatory influence of ACTH on the adrenocortical mitochondrial synthesis of pregnenolone in response to ACTH was studied in adrenal mitochondria isolated from control guinea-pigs and from animals treated s.c. with 100 micrograms ACTH(1-24) twice daily on the day before the animals were killed. The animals from both groups were injected with 100 micrograms ACTH s.c. 30 min before killing. The mitochondrial production of pregnenolone (expressed in nmol per mg mitochondrial protein after 10-min incubation) increased from 1.52 +/- 0.46 (S.E.M.) in the control group to 4.50 +/- 0.59 for mitochondria from ACTH-treated animals, despite a similar free cholesterol content in the mitochondria, even when determined after a previous in-vivo treatment with aminoglutethimide to block further metabolism of cholesterol into pregnenolone. In addition, in the presence of an excess of exogenous cholesterol (100 mumol/l), the production of pregnenolone remained higher for mitochondria from ACTH-treated animals. In contrast, when the calcium concentration in the incubation medium was raised to 1 mmol/l, with subsequent enhancement in pregnenolone synthesis, the mitochondrial pregnenolone production became similar for both groups (8.28 +/- 1.11 nmol in the ACTH-treated group and 9.55 +/- 1.90 nmol in the control group), even in the presence of 100 mumol cholesterol/l (13.5 +/- 1.80 nmol in ACTH-treated animals and 14.8 +/- 1.93 nmol in controls). Cycloheximide treatment administered on the day before the animals were killed was without any effect on pregnenolone production in control animals (3.51 +/- 0.43 nmol before and 3.65 +/- 0.63 nmol after cycloheximide treatment).(ABSTRACT TRUNCATED AT 250 WORDS)     

Problems posed by the association of hemophilia A and congenital adrenal hyperplasia caused by 21-hydroxylase deficiency

Association of congenital adrenal hyperplasia (21 hydroxylase deficiency) and hemophilia A in one child is reported; the authors insist about the rarity and the genetic implications of this association in case of other children.     

The interactions between plasma membrane depolarization and glutamate receptor activation in the regulation of cytoplasmic free calcium in cultured cerebellar granule cells

The complex modulation of cytoplasmic free calcium concentration ([Ca2+]c) in primary cultures of cerebellar granule cells in response to glutamate receptor agonists has been the subject of several contradictory reports. We here show that 3 components of the [Ca2+]c response can be distinguished: (1) Ca2+ entry through voltage-dependent Ca2+ channels, following KCl- or receptor-evoked depolarization, (2) Ca2+ entry through NMDA receptor channels, and (3) liberation of internal Ca2+ via a metabolotropic receptor. Depolarization with KCl induced a transient [Ca2+]c response (subject to voltage inactivation) decaying to a sustained plateau (largely inhibited by nifedipine). The NMDA response was potentiated by glycine, totally inhibited by (+)5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), and blocked by Mg2+ in a voltage-sensitive manner. Polarized cells displayed small responses to quisqualate (QA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA). Depolarization enhanced a transient response to QA, but not to AMPA. Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD), a selective agonist for the metabolotropic glutamate receptor, caused a transient elevation of [Ca2+]c, which was blocked by prior exposure to QA but not AMPA. The prolonged [Ca2+]c response to kainate (KA) can be resolved into 2 major components: an indirect NMDA receptor-mediated response due to released glutamate and a nifedipine-sensitive component consistent with depolarization-mediated entry via Ca2+ channels. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX), QA at greater than 10 microM, and AMPA (but not trans-ACPD) reversed the KA response, consistent with an inactivation of the KA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Erythema dyschromicum perstans

A 29-year-old woman from Trinidad experienced the rapid onset of extensive lesions characteristic of erythema dyschromicum perstans following an x-ray study using orally administered contrast. Eleven months later a skin biopsy specimen showed few epidermal changes but extensive incontinence of melanin pigment and marked dilatation of lymphatics in the superficial dermis. Results of a systemic evaluation were normal. The available data on this disease are analyzed and conclusions offered regarding its nature and causes.     

THE INFLUENCE OF MOUSE-RAT PARABIOSIS ON THE GROWTH IN RATS OF A TRANSPLANTABLE MOUSE SARCOMA

The results in these experiments seem to justify us in concluding that the growth of mouse tumors in rats is very definitely promoted by mouse-rat parabiosis, the percentage of " takes" being markedly increased, the rate of growth accelerated, and the duration of active growth extended to at least seventeen days. These findings are in accord with Ehrlich''s hypothesis, although, on account of the complexity of the factors involved in such experiments, other explanations may be advanced.     

Innovation within the federal healthcare services: initiatives and promises

Within the healthcare services industry, innovation is offered as a process for ameliorating issues, improving services, and getting the most out of scarce resources. Medical Services in the Army, Navy, Air Force, Veterans Administration, and the Public Health Service have formed a Federal Healthcare Innovation Network (FHIN) to optimize the use of this management tool. In this article, the concept of innovation in healthcare services management and delivery is reviewed, initiatives in innovation within the five federal healthcare services are discussed, and the promises innovation holds for improved healthcare delivery are addressed.