Alan N. Elias

EFFECTS OF VALPROIC ACID, NALOXONE AND HYDROCORTISONE IN NELSON'S SYNDROME AND CUSHING'S DISEASE

Two patients with Nelsons syndrome and one patient after bilateral adrenalectomy for Cushings disease, without any evidence of Nelsons syndrome, were studied with respect to the effect of hydrocortisone, naloxone and valproic acid (a GABA transaminase inhibitor) on ACTH secretion. Hydrocortisone suppressed plasma ACTH concentrations to normal in the patient without Nelsons syndrome, but failed to do so in the two patients with Nelsons syndrome. Naloxone and valproic acid caused a decline in plasma ACTH concentrations in the patients with Nelsons syndrome, but produced no change in the patient without Nelsons syndrome. Secretion of ACTH may thus be influenced by both opiate peptides and by gamma aminobutyric acid, as well as by the cortisol concentrations, these agents may act at different sites to inhibit ACTH release by the tumour.

Leptin and IGF-I levels in unconditioned male volunteers after short-term exercise.

We have previously shown that serum gonadotropins, particularly LH, decline after acute exercise in male volunteers. The mechanism for this decline is unknown. Plasma leptin and IGF-I concentrations were measured in seven male volunteers after acute exercise to exhaustion using the Bruce protocol. Leptin concentrations declined following exercise reaching nadir values 30-120 min after exercise. As anticipated, plasma IGF-I concentrations showed a transient rise immediately after exercise falling thereafter to nadir levels 60-90 min after exercise before returning towards baseline levels. In view of the previously described decline in gonadotropin release after acute exercise, the decline in plasma leptin levels, perhaps related to the rise in IGF-I, may play a role in exercise-induced inhibition of gonadotropin release presumably by inhibition of GnRH secretion.

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.

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.

Abnormalities in Glucose Metabolism in Patients with Schizophrenia Treated with Atypical Antipsychotic Medications

The incidence of carbohydrate intolerance and overt diabetes is increased in patients with schizophrenia treated with the newer atypical antipsychotic agents. The precise mechanism for these abnormalities remains obscure. This review examines the potential interaction between atypical antipsychotic medications and several hormones known to influence appetite regulation and carbohydrate metabolism.

Effects of some clinically encountered drugs on steroid synthesis and degradation

TEROID HORMONES and their synthetic analogues are extensively used as antiinflammatory agents, immunosuppressants, and contraceptives, and often used in combination with other drugs. The interaction between steroids and other drugs is complex and may involve alterations in steroid hormone secretion, excretion, metabolic degradation, and steroidogenesis. Knowledge of drug-steroid interactions, therefore, becomes a matter of practical concern to the physician caring for patients who receive steroids along with a variety of other medications. This review will focus on the interactions between steroids and some commonly used and interesting drugs. Drugs influence steroid metabolism by altering the peripheral degradation of the steroid, inhibiting steroidogenesis, or affecting the hypothalamus or pituitary with resultant alterations in steroid production. This article will review the first two mechanisms.

Effect of orally administered antithyroid thioureylenes on PCNA and p53 expression in psoriatic lesions

Background. Antithyroid thioureylenes are effective agents in the oral and topical treatment of patients with chronic plaque psoriasis.

Effects of Blood pH and Blood Lactate on Growth Hormone, Prolactin, and Gonadotropin Release after Acute Exercise in Male Volunteers

Abstract It has recently been found that prevention of the acidosis of anaerobic exercise blocks β-endorphin release. Because heavy exercise affects secretion of other anterior pituitary hormones, we studied the results of alkali infusion and ingestion upon blood levels of four hormones: luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). Eight male subjects were studied after either 2 mEq/kg placebo (NaCl) or alkali (NaHCO3) administered before and during exercise to exhaustion. Blood samples were obtained before exercise and then 15, 30, 60, 90, 120, and 180 min postexercise. GH and PRL but not FSH or LH increased significantly postexercise, with a peak at 60 min, and subsequently declined back to baseline by 180 min. Base treatment reduced GH at baseline and postexercise (except at 60 min) and increased PRL significantly, particularly at 60 min. While the precise mechanisms on how acid/base changes affect hormone release remain to be defined, there are possible consequences on gonadal function and substrate availability during exercise.

Melatonin and gonadotropin secretion after acute exercise in physically active males

SummarySerum concentrations of luteinizing hormone (LH), follicle stimulating hormone, testosterone (T) and melatonin were measured in seven physically active male volunteers after exercise on a treadmill using the Bruce protocol. Measurements were made on blood samples obtained before exercise, within 30 s after exercise, at 15 min after exercise, and subsequently at 30-min intervals after exercise for a total duration of 180 min. Serum LH concentration fell from a peak post-exercise level of 15.7 (4.7) IU·l−1 [mean (SD)] to a nadir of 10.3 (2.4) IU·l−1 (P<0.004). Nadir values in individual volunteers were seen between 60 and 150 min after exercise. This fall in serum LH was paralleled by a similar fall in the concentration of serum T. Serum melaonin concentrations did not change significantly after exercise. It is concluded that melatonin, despite is reported anti-gonadotropic properties, does not play a role in the depression of serum LH after acute strenuous exercise in physically active males

ACTH Stimulation of Adrenal Epinephrine and Norepinephrine Release

Epinephrine (E) and norepinephrine (NE) levels were measured simultaneously in the adrenal veins of 6 patients before and after stimulation with 0.25 mg beta 1-24 ACTH. In 1 patient with Cushings syndrome, E and NE were also measured before and 30 min after dexamethasone. There was a significant increase in NE and E secretion (p less than 0.002) from both adrenal glands after ACTH stimulation. In the patient with Cushings syndrome, there was also a slight increase in plasma E levels after dexamethasone. It is postulated that ACTH stimulated NE and E secretion by augmenting blood flow through the adrenals and by induction of tyrosine hydroxylase and dopamine beta-hydroxylase, although a direct effect of ACTH on NE and E secretion cannot be excluded. It is also possible that the increase in adrenal catecholamine secretion after ACTH may be due to ACTH augmentation of catecholamine secretion by endogenous opioids such as beta-endorphin.