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Biomedical subjects

A N Elias

Publications and source records attributed to A N Elias.

At least 19 recordsLinked to original sources

Effective portal insulin delivery with enzyme-protected capsules in pancreatectomized pigs.

1. Plasma concentrations of insulin, C-peptide, glucagon and glucose were measured in surgically pancreatectomized pigs given insulin into the colon directly and in enteric peptidase-resistant (methacrylic acid copolymer-encapsulated) form. 2. Following introduction of insulin-containing capsules, plasma insulin concentration rose from 2.7 +/- 0.1 microU/ml to 110.9 +/- 51.9 microU/ml in the portal vein, and from 2.6 +/- 0.1 microU/ml to 26.9 +/- 7.3 microU/ml in the systemic circulation. Corresponding portal and systemic values after direct (non-encapsulated) insulin instillation were 28.2 +/- 15.9 microU/ml to 44.8 +/- 13.0 microU/ml and 7.5 +/- 2.6 microU/ml to 15.2 +/- 2.5 microU/ml respectively. Insulin concentrations peaked at 75 min in the group as a whole and between 60-90 min in individual animals. Absorption was most pronounced in pigs given aprotinin (a trypsin inhibitor) with insulin. 3. Plasma portal vein glucose concentrations fell from 76.2 +/- 8.9 mg/dl to 31.1 +/- 3.2 mg/dl 150 min after encapsulated insulin administration. Corresponding systemic glucose levels were 84.5 +/- 11.0 mg/dl and 37.0 +/- 1.4 mg/dl. 4. Colonic administration of insulin in methacrylic acid coated capsules results in peak portal and systemic insulin levels 60-90 min after administration. Co-administration of aprotinin enhances the fraction of insulin absorbed.

Animals

Are all males equal? Anatomic and functional basis for sexual orientation in males.

In non-human primates anterior hypothalamic nuclei are closely involved in heterosexual activity in males. In humans, hypothalamic nuclei which correspond to these nuclei in non-human primates have been shown to have a neuronal density in homosexual men that is approximately half of that seen in heterosexual men. In addition, homosexual men exhibit a positive luteinizing hormone response to acutely administered estrogen that is intermediate between women (flat response) and heterosexual men (exaggerated response). Furthermore, on the basis of serum testosterone concentrations in similarly feminized transsexual males on estrogen/progestogen treatment 3 distinct groups can be identified. It is postulated that anatomic differences in the anterior hypothalamic nuclei that regulate sexual orientation in males may lead to alteration in the gonadotropin releasing hormone (GnRH) pulse/frequency leading to a more female-type pattern of gonadotropin secretion in homosexual males. Based on data in transsexual males this pattern may be more or less of the female-type in subsets of male homosexuals.

Animals

Immobilization osteoporosis in paraplegia.

The pathophysiology of osteoporosis as it relates to immobilization or disuse osteoporosis in paraplegics is briefly reviewed. The physiology of bone formation and resorption is discussed, and the influence of piezoelectric forces on bone integrity and the consequences of the loss of this effect in paraplegics is addressed. When bone is stressed, negative charges accumulate on the side from which the stress is applied and positive charges accumulate on the opposite side. Presumably the collagenous component of bone plays the major role in the generation of electrical potentials. Another mechanism important in the generation of electrical potentials is created by liquid planes streaming past solid planes. Diminished forces acting on bone, as in paraplegia, are translated into changes in the activity of bone remodeling units which can be assessed by histomorphic and histoenzymatic techniques. Other biochemical and endocrine consequences of immobilization involve increased serum calcium, decreased serum parathyroid hormone (PTH), and decreased dihydroxy-vitamin D synthesis. Urinary hydroxyproline and calcium excretion are increased, as is stool calcium. The bone loss that follows immobilization may produce an increased susceptibility to fractures involving long bones more than the spinal column, and is due more to decreased bone formation than to accelerated bone resorption. The treatment of immobilization osteoporosis primarily involves early remobilization, but other treatments, including the use of electrical fields and the administration of bisphosphonates, calcitonin, and a growth hormone are being actively investigated.

Bone and Bones

Nelson's syndrome.

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Adrenocorticotropic Hormone

The pituitary-gonadal axis in experimental nephrotic syndrome in male rats.

Basal and luteinizing releasing hormone-stimulated gonadotropin secretion were studied in male rats made nephrotic with puromycin, and in pair-fed and normal control animals. In addition, plasma concentrations of testosterone, androstenedione, estradiol, and estrone were measured in the three groups of animals. Urinary testosterone concentrations were also measured in the three experimental groups. The data showed that basal luteinizing hormone concentration was significantly elevated in the nephrotic group compared with the pair-fed and normal control groups. Gonadotropin response to luteinizing releasing hormone stimulation was not significantly different in the three groups, suggesting an intact hypothalamic-pituitary axis in nephrotic syndrome. Urinary testosterone concentration in the nephrotic animals was significantly higher than in the pair-fed and normal control groups. Plasma testosterone, androstenedione, estradiol, and estrone concentrations were significantly lower in the nephrotic and pair-fed animals than in the normal control animals, indicating possibly impaired gonadal steroidogenesis in these two groups that may be related to the catabolic state of the animals. It thus appears that urinary loss of protein-bound (sex hormone binding globulin-bound) testosterone in the nephrotic syndrome leads to increased basal secretion of luteinizing hormone, presumably as a result of increased luteinizing releasing hormone secretion. This occurs to compensate for the abnormal urinary testosterone loss and is an attempt to restore plasma testosterone concentrations to normal. The higher basal plasma luteinizing hormone concentration in the nephrotic group supports this conclusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hormone pattern in pharmacologically feminized male transsexuals in the California State prison system.

The hormonal profile of 40 transsexual inmates from a pool of 86 inmates in the California State prison system was studied before and after therapy with feminizing hormones. Clinical and social data were obtained on all 86 inmates; the incidence of human immunodeficiency virus (HIV) seropositivity was examined in 76 of the 86 individuals. Despite similar degrees of feminization in all 40 individuals in whom hormonal studies were performed, variable suppression of serum testosterone concentrations was present. Based on their testosterone concentrations while on feminizing hormone therapy, the transsexual inmates could be divided into three groups. In Group I (the "suppressed" group), the serum testosterone concentrations were markedly depressed (less than 10 ng/dL); in Group II (the "non-suppressed" group), the values of testosterone were normal (446 to 1072 ng/dL); and in Group III (the "intermediate" group), the testosterone values were between those of the suppressed group and the nonsuppressed group. We speculate that feminizing hormone therapy may induce the development of a state of target hormone resistance to testosterone that results in similar degrees of feminization independent of the circulating concentrations of testosterone. The incidence of HIV seropositivity (3/76) was considerably less than anticipated based on previous studies in populations at high risk for developing the acquired immunodeficiency syndrome.

Adult

The endocrinology and pathophysiology of alcoholic cirrhosis and functional renal failure--a review.

The pathophysiology and characteristics of decompensated alcoholic cirrhosis and functional renal failure are reviewed. The review will be restricted to alcoholic cirrhosis, because most cases of functional renal failure in the United States occur in the setting of alcoholic cirrhosis, which is also the most common cause of ascites in North America and Europe. Moreover, hepatorenal syndrome may complicate other forms of liver disease besides alcoholic cirrhosis, but the pathogenesis in such circumstances may not be the same as in the cirrhotic state.

Ascites

Corticotropin releasing hormone and gonadotropin secretion in physically active males after acute exercise.

Plasma concentrations of corticotropin releasing hormone (CRH) and the serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, adrenocorticotropic hormone (ACTH) and cortisol were measured in seven physically active males after acute exercise on a treadmill using the Bruce protocol. Measurements were made in the basal pre-exercise state, immediately after exercise, and at 30-min intervals for 3 h after exercise. Serum LH concentrations declined following exercise reaching nadir values between 60 and 180 min after exercise (90 min post exercise in the group). The nadir values in individual volunteers were significantly lower than both the baseline and post-exercise levels. This fall in serum LH concentration appeared to follow a slight but significant elevation of the plasma concentration of CRH which reached peak levels when measured immediately post exercise. Plasma ACTH concentrations paralleled the rise in CRH, but fell to undetectable levels of below 13.8 nmol.l-1 (less than 5 ng.l-1) 60 min after exercise. Plasma cortisol concentrations peaked approximately 30 min after the rise in ACTH, after which they gradually declined to baseline levels. Plasma testosterone concentrations paralleled the concentrations of LH. The data suggest that CRH, on the basis of its previously described gonadotropin-depressant property, may be the hormone involved in the exercise-mediated decline in serum LH. Alternatively, some as yet unidentified factor(s), may be involved in producing the altered concentrations of both LH and CRH.

Adrenocorticotropic Hormone

Insulin and C-peptide levels following oral administration of insulin in intestinal-enzyme protected capsules.

1. Crystalline beef insulin was administered orally in capsules composed of a methacrylic acid copolymer which prevented breakdown of the insulin by enteric and pancreatic peptidases. 2. In studies performed in 3 individuals blood was sampled before oral ingestion of the insulin (40 144 units), and at 15 or 30 min intervals thereafter for 5.5 hr for measurement of immunoreactive insulin and C-peptide concentrations. 3. Following the administration of oral insulin, plasma immunoreactive insulin concentrations became elevated 4-5 hr after ingestion. 4. The rise in plasma insulin concentrations was associated with a corresponding fall in the concentration of C-peptide. 5. The data suggest that this preparation of oral insulin can produce significant enteric absorption of the peptide, and that further investigation of agents that facilitate insulin absorption from the gut might render the use of methacrylic acid copolymer coated capsules a physiologically sound and a commercially feasible method of oral insulin administration.

Administration, Oral

Hypothesis: insulin is responsible for the vascular complications of diabetes.

It is proposed that the systemic hyperinsulinemia and hepatic portal hypoinsulinemia that occurs with conventional injectable preparations of insulin currently used in the treatment of patients with diabetes mellitus is largely responsible for the morbidity associated with this disease. Epidemiological evidence and animal experimentation strongly support systemic hyperinsulinemia as a major factor in genesis of atherosclerosis in diabetic patients. In addition, in vitro studies demonstrate a direct effect of insulin on endothelial cell and arterial smooth muscle proliferation. On the other hand, inadequate hepatic delivery of insulin is associated with overproduction of renal vasoregulatory factors leading to glomerular hyperfiltration and ultimately to glomerulosclerosis and its clinical endpoint--end-stage renal disease. In the absence of widespread success of pancreatic and islet-cell transplantation as a means to deliver insulin physiologically into the hepatic portal circulation, methods must be devised and perfected to accomplish such delivery using approaches such as orally administering insulin in intestinal-enzyme protected capsules. Until such methods of delivery are available for safe and widespread use, one should abandon the illusory goal of rigid glucose control in favor of methods that reduce insulin requirement. Along these lines, dietary restriction and aerobic exercise should be the major life style changes advised for diabetic patients. Reduction of glomerular hyperfiltration in diabetic patients can be promoted with the use of low protein diets and/or angiotensin converting enzyme inhibitors.

Animals

Inhibin and gonadotrophin secretion in physically active males after acute exercise.

Serum concentrations of luteinizing hormone (LH) follicle stimulating hormone (FSH), testosterone and inhibin were measured in six physically active male volunteers after heavy exercise on a treadmill. Hormone measurements were made before exercise, immediately after exercise and at 30-min intervals for 3 h after exercise. Serum concentrations of LH fell after exercise reaching nadir values between 60 and 180 min post-exercise. The nadir value of LH for the group as a whole occurred 90 min after exercise. Serum testosterone concentrations paralleled the changes in LH concentrations. Serum FSH and inhibin concentrations did not show any appreciable change from baseline values. The data suggest that acute exercise does not significantly lower serum concentrations of FSH or inhibin. Whether repetitive and prolonged heavy exercise, as in competitive runners, produces alterations in serum inhibin concentrations remains to be determined.

Adult

Glomerulopressin activity in carbon tetrachloride-induced cirrhosis in male rats.

The activity of glomerulopressin, a putative renal vasoregulatory hormone that is synthesized in the liver, was assayed in male rats with carbon tetrachloride-induced cirrhosis and the results were compared to glomerulopressin activity in normal-control and pair-fed animals. Glomerulopressin activity in blood samples collected from the hepatic vein of the cirrhotic group was significantly lower than the activity in the normal-control and pair-fed groups. Glomerulopressin activity in the normal-control and the pair-fed groups were not significantly different. The data support the concept that glomerulopressin deficiency in liver disease, such as cirrhosis, may play a role in the genesis of the functional renal failure associated with liver disease.

Animals

Concentrations of volume-regulatory hormones after acute exercise in physically conditioned males.

Plasma renin activity and plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP) and aldosterone (Aldo) were determined in six physically conditioned male volunteers and five unconditioned volunteers who served as controls. All volunteers were subjected to acute exercise for 15 min or until exhaustion. In the conditioned volunteers, the plasma concentrations of all hormones did not change when compared with pre-exercise values measured immediately after and 60 min after exercise. Similarly, plasma renin activity (PRA) after exercise was unchanged when compared with pre-exercise levels. In contrast, the unconditioned volunteers showed elevation of the plasma concentrations of AVP, and Aldo. PRA also increased in the unconditioned volunteers, but plasma ANP concentrations were not significantly different from base-line pre-exercise levels. These data suggest a decrease in central volume with exercise in the unconditioned individuals, which probably does not occur in the conditioned individual because of adaptive mechanisms. The data also suggest that in the physically conditioned individual, significant atrial distention with resultant release of atrial natriuretic peptide does not occur, or alternatively, that significant atrial distention in these subjects fails to produce the expected release of atrial natriuretic peptide. In the unconditioned individual, the postulated decrease in effective central volume following exercise would not be expected to trigger any rise in ANP.

Adult

Oral insulin.

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Administration, Oral