demeclocycline and Body-Weight

Osteoporosis in men is a disease that is increasing in incidence, and with an increasing elderly population it poses a serious health problem. Since both testosterone (T) and growth hormone (GH) have an anabolic effect on bone and both decrease with aging, we were prompted to test whether the administration of these hormones in combination would increase bone mass in orchiectomized (orx) senile rats more than administration of either agent alone. Twenty-month-old male Wistar rats were divided into five groups with seven animals each: (a) age-matched intact control, (b) orx, (c) orx+GH (2.5 mg/kg/day), (d) orx+T [10 mg/kg, subcutaneous (s.c.), injection given twice a week], and (e) orx+GH+T. Testosterone and GH were given subcutaneously for 4 weeks. Bone histomorphometry of the tibial shaft showed that the orx group had lower cortical bone area than the intact control group. The decrease in cortical bone area was due to increased intracortical porosis as well as decreased periosteal bone formation rate (BFR). Administration of T to the orx animals prevented the development of the porosis and the decrease in periosteal BFR. The bone mineral content (BMC) and bone mineral density (BMD) of the femur as tested by dual-energy X-ray absorptiometry were significantly higher in the orx+T than in the orx group and were not significantly different from that of the intact control group. Administration of GH to the orx rats increased periosteal BFR significantly; however, the BMC and BMD measured were not increased significantly in comparison to the orx group. When GH and T were combined in treatment, the cortical bone area, periosteal BFR, and femoral BMD were all significantly higher than that of the orx and even higher than the intact control rats. Two-way analysis of variance shows that the individual effect of GH and T treatment on the periosteal BFR and cortical bone area was significant. The effect of T, but not GH, on femoral BMC and BMD was also significant; however, there is no synergistic interaction between the two treatments. Four weeks of orx with or without GH or T administration had no significant effect on tibial metaphyseal cancellous bone volume. In conclusion, this short-term study suggests that the combined intervention of GH and T in androgen-deficient aged male rats may have an independent effect in preventing osteopenia. The significant effect of GH+T may be attributed to the prevention of intracortical porosis, and an increase in periosteal bo

Topics: Absorptiometry, Photon; Aging; Animals; Body Weight; Bone Density; Bone Development; Demeclocycline; Drug Synergism; Femur; Human Growth Hormone; Humans; Male; Orchiectomy; Rats; Rats, Wistar; Testosterone

In most diabetic patients, the presence of hyponatremia is usually ascribed to severe hyperglycemia, hypertriglyceridemia, oral hypoglycemic agents, or other drugs. We describe two insulin-treated type II diabetic patients who were seen with severe rapid weight loss, hyponatremia, and diabetic amyotrophy despite good metabolic control. Laboratory evaluation of the hyponatremia suggested the syndrome of inappropriate antidiuretic hormone secretion. Their clinical presentations led to the suspicion of an underlying malignant neoplasm in each case. One patient required demeclocycline for treatment of his symptomatic hyponatremia, while the other improved with fluid restriction and intermittent furosemide therapy. The hyponatremia resolved spontaneously with improvement in body weight and the amyotrophy resolved after four to six months. After 24 to 36 months of close follow-up, no evidence of malignancy has been documented in either of the patients. We conclude that this clinical entity of amyotrophy is benign and should be included in the differential diagnosis of chronic hyponatremia in diabetic patients.

Topics: Atrophy; Body Weight; Demeclocycline; Diabetes Mellitus, Type 2; Electrolytes; Furosemide; Humans; Hyponatremia; Male; Middle Aged; Muscular Diseases; Sodium Chloride

We examined renal function and Na+ balance in a patient with congestive heart failure who was treated with demeclocycline (DMC) on three separate occasions under strict metabolic balance conditions. Natriuresis and reversible renal insufficiency, which could not be explained solely on the basis of negative Na+ balance, developed on each occasion. In contrast to reports of an association between elevated serum DMC levels and renal insufficiency in patients with cirrhotic edema, the renal insufficiency in this patient with cardiac edema occurred in the absence of high DMC levels. Consequently, markedly elevated serum DMC levels do not appear to be a prerequisite for the development of natriuresis or renal insufficiency in edematous patients receiving this drug. In an attempt to clarify the mechanism of the natriuresis, we also examined the effects of DMC on Na+ transport in an in-vitro model system, the toad urinary bladder. DMC inhibited aldosterone-stimulated Na+ transport, but had no effect on Na+ transport when the latter was jointly stimulated by ADH and theophylline. Despite this selective inhibition of the natriferic effect of aldosterone in vitro, it is unlikely that such a mechanism completely accounts for the natriuresis observed in-vivo since the natriuresis is generally of large magnitude and is usually accompanied by some degree of kaliuresis, and DMC had no consistent effect on urinary aldosterone excretion. Consequently, other mechanisms must be sought to explain the natriuretic effect of DMC in edematous patients. Likewise, mechanisms other than negative Na+ balance (perhaps primary alterations in renal hemodynamics) must underly the development of renal insufficiency in such individuals.

Topics: Administration, Oral; Aldosterone; Animals; Anura; Biological Transport; Blood Urea Nitrogen; Body Weight; Demeclocycline; Glomerular Filtration Rate; Heart Failure; Humans; In Vitro Techniques; Kidney Failure, Chronic; Male; Middle Aged; Natriuresis; Nephrons; Potassium; Sodium; Theophylline; Vasopressins

A case of tuberculous Addison's disease presenting with psychosis, profound hyponatraemia, and detectable plasma antidiuretic hormone is reported. Clinical and biochemical improvement after corticosteroid replacement was followed by relapse with further psychosis and inappropriate antidiuretic hormone secretion: both were promptly reversed by demethylchlortetracycline. The association of psychological symptoms with Addison's disease, the role of anti-diuretic hormone secretion in Addison's disease, and the inter-relationship between Addison's disease, psychosis and anti-diuretic hormone secretion are discussed.

Topics: Addison Disease; Body Weight; Demeclocycline; Fludrocortisone; Humans; Hydrocortisone; Inappropriate ADH Syndrome; Male; Middle Aged; Psychotic Disorders; Vasopressins; Water Intoxication

Studies were performed in conscious rats to evaluate the role of renal prostaglandin biosynthesis in demeclocycline-induced polyuria. Three groups of animals were evaluated. Group 1 animals received only the diluents used for both demeclocycline and indomethacin. Group 2 received demeclocycline (20 mg/kg/day) and the indomethacin diluent. Group 3 received both demeclocycline and indomethacin (10 mg/kg/day). After eight days of demeclocycline administration, urine flow rate increased in the group 2 animals from 15.1 +/- 2.1 to 31.1 +/- 5.1 ml/day. Indomethacin failed to alter the magnitude of demeclocycline-induced polyuria despite a 60% reduction in urine prostaglandin E excretion rats. These studies demonstrate that the concentrating defect induced by demeclocycline can occur independent of alterations in praostaglandin biosynthesis and suggest that a change in renal prostaglandin biosynthesis is not an etiologic factor in demeclocycline-induced polyuria.

Topics: Animals; Body Weight; Demeclocycline; Female; Glomerular Filtration Rate; Indomethacin; Polyuria; Prostaglandin Antagonists; Prostaglandins E; Rats

Topics: Body Weight; Demeclocycline; Diuresis; Edema, Cardiac; Heart Failure; Humans; Natriuresis

Topics: Acne Vulgaris; Acute Kidney Injury; Body Weight; Chemical and Drug Induced Liver Injury; Demeclocycline; Diabetes Insipidus; Drug Eruptions; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Infections; Photosensitivity Disorders; Pregnancy; Tetracyclines; Time Factors