UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last 25 years, the perceived clinical spectrum of primary hyperparathyroidism (HPT) has changed dramatically from a disorder characterized by severe bone and renal disease to one typically manifested by few or mild symptoms and little evidence of organ damage. Reasons for this change in spectrum include changing demographics (primary HPT is primarily a disease of the middle-aged and elderly), diffusion of medical knowledge leading to a higher index of suspicion, and improved clinical laboratory technology (especially inexpensive and accurate determination of serum calcium and parathyroid hormone). In the first 343 cases of primary HPT seen at the Massachusetts General Hospital, 57% had renal stones, 23% had hyperparathyroid bone disease, and less than 1% had no symptoms. By contrast, studies dating from the availability of automated serum calcium measurement found renal stones and hyperparathyroid bone disease in less than 5% of cases, and about half of cases had few or no symptoms. Most patients with primary HPT today have mild, nonspecific symptoms, such as weakness, fatigue, and mental depression, and such signs as arterial hypertension and osteopenia, and detection of their hypercalcemia is generally serendipitous. The mildness and slow progression seen in many cases of primary HPT has resulted in much controversy about appropriate management.
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PMID:Clinical spectrum of primary hyperparathyroidism: evolution with changes in medical practice and technology. 176 71

Treatment of osteoporosis with a complete reconstruction of the normal three dimensional architecture of trabecular bone is an unsolved problem. In addition to the well established fluoride therapy new concepts in the treatment of osteoporosis were developed. There is growing interest in the so called ADFR concept (activation, depression of resorption, formation, repeat the cycle) as a physiological stimulation of osteoblastic bone formation. The histological results following ADFR treatment in 8 patients are reported. After 12 months of treatment with parathyroid hormone [1-38)hPTH) (stimulation of the basic metabolic units) and the diphosphonate EHDP (depression of osteoclastic resorption) no change of remodelling processes at the trabecular bone surface could be observed. The results demonstrate many doubts in the importance of the ADFR concept for the treatment of osteoporosis.
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PMID:[Morphologic study of iliac crest spongiosa in patients with osteoporosis treated according to the ADFR (activation, depression of resorption, formation, repeat the cycle) with parathyroid hormone and diphosphonates (Hannover PTH I study)]. 213 78

Previous work demonstrated that parathyroid hormone (PTH) activates the Ca2+/protein kinase C (PKC) system in addition to cAMP production. Therefore, the authors explored the role of cAMP-dependent and Ca2(+)-dependent signals in the regulation of osteoblastic growth and bone resorption. In exponentially growing UMR 106-01 osteogenic sarcoma cells, PTH (10(-7) M) inhibited [3H] thymidine incorporation by 80%. This effect was reproduced by maximal doses of both dibutyryl-cAMP (dbcAMP) and forskolin. The Ca2+ ionophore ionomycin (10(-7) M) had no effect, whereas phorbol 12-myristate 13-acetate (PMA) was slightly mitogenic. The antimitogenic action of dbcAMP was dose-dependent, with ED0.5 at about 3 X 10(-5) M. Ionomycin enhanced this dbcAMP effect at submaximal doses of the cAMP analog. PMA used in combination with both dbcAMP and ionomycin induced further depression of cell proliferation, indicating synergism with cAMP. Both dbcAMP (10(-4) M) and ionomycin (10(-7) M) stimulated 45Ca release from fetal rat limb bones after five days in culture, although the Ca2+ ionophore was less potent. 1-Oleoyl 2-acetyl-glycerol (2 X 10(-6) M) was ineffective alone, and slightly inhibited the 45Ca release produced by the other second messenger analogs in all combinations. The combination of dbcAMP and ionomycin showed a synergistic effect, and fully reproduced PTH effect. In conclusion, PTH signal transduction for control of cell proliferation and bone resorption is mediated mainly by cAMP. Activation of the Ca2+/PKC message system is nevertheless necessary to express a full hormonal response in both cell and organ culture systems.
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PMID:Cyclic AMP-dependent and calcium-dependent signals in parathyroid hormone function. 217 68

It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pHi), and there is some evidence that this in turn may influence cell growth. We have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein indicated that these cells regulate pHi by means of an amiloride-inhibitable Na+-H+ exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pHi with a half-maximal effect at 10(-11) M. At 1 h, the maximal depression of pHi was 0.1 +/- 0.01 U. This effect was reproduced by forskolin, but neither agent influenced pHi in the presence of amiloride. Incorporation of [3H]thymidine was reduced by rPTH (half-maximal dose approximately 10(-11) M), forskolin, and N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pHi and [3H]thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of [3H]thymidine incorporation in the presence of amiloride, even though it did not affect pHi in these circumstances. It is concluded that PTH decreases pHi and growth in UMR 106 cells but that these changes can be dissociated. Depression of pHi may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment.
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PMID:Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells. 283 40

Cardiac dysfunction is common in patients with terminal renal failure. However, no consensus has been reached with respect to the indications for digitalis therapy. Depression of myocardial contractility may occur as a result of circulating toxic factors, parathyroid hormone, and altered catecholaminergic responsiveness. On the other hand, paradoxical positive inotropic effects have been observed possibly as a result of a circulating natriuretic factor (an endogenous digitalis analogue) which inhibits Na,K-ATP'ase. Pharmacokinetics and pharmacodynamics of digitalis steroids are altered in uremia. Elimination half-lives of strophanthin and digoxin are prolonged, whereas the elimination half-life of digitoxin is unchanged. Altered protein binding and volume of distribution have been noted. Despite its long elimination half-life, most nephrologists favor administration of digitoxin because of its insensitivity to changes in renal function.
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PMID:Digitalis in chronic renal insufficiency. 300 26

The multisystem involvement in acute pancreatitis (AP) is a reflection of the pancreatic gland's capacity to produce a number of potent vasoactive peptides, hormones, and enzymes. The various prognostic criteria are early evaluations of these metabolic derangements. The pathogenesis of hypocalcemia, long recognized as an indicator of severity of AP, is multifactorial. Imbalances of parathyroid hormone (PTH)-calcitonin, the interactions of glucagon, gastrin and other pancreatic hormones with PTH-calcitonin, the role of free fatty acids in binding serum calcium with albumin, and the translocation of calcium ion in muscles and liver, have been recently described but remain conflicting theories. Yet, the time-honored theory of calcium-soap formation enjoys wide acceptance. Hyperglycemia, hypoglycemia, and occasional ketoacidosis in acute pancreatitis have been studied thoroughly. The complex cause-and-effect relationship between hyperlipidemia with acute pancreatitis needs further study. The coagulation abnormalities seem to be initiated by activated trypsin, and their role in microvascular coagulation appears to form a unifying hypothesis for major organ dysfunction, but this requires further investigation. Adult respiratory distress syndrome may be the result of active enzymes that digest pulmonary surfactant and/or microvascular thrombosis. The depression of cardiac function and shock are suspected to be secondary to vasoactive peptides such as bradykinin, or myocardial depressant factor, whose structure has yet to be elucidated. The renin-angiotensin alterations and renal complications in acute pancreatitis have received scant attention in the literature. The onset of moderate visual disturbances, or even blindness, in a patient with acute pancreatitis as a result of retinal vessel thrombosis is fortunately uncommon. Rare but interesting are the manifestations such as subcutaneous fat necrosis, arthralgia, and pancreatic encephalopathy. Despite the extensive literature on the complexities of the pathogenesis of complications of acute pancreatitis, there have been very few advances in the prevention and management of specific complications. It is hoped that further work on modification of enzymatic disturbances induced in acute pancreatitis will result in its effective treatment and prevention of serious complications.
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PMID:Systemic complications of acute pancreatitis. 328

We measured nephrogenous cyclic adenosine monophosphate (NcAMP) excretion, an in vivo bioassay for endogenous parathyroid hormone (PTH) secretion, and renal phosphate threshold (TmP/GFR) in 33 renal allograft recipients with stable renal function (creatinine clearance greater than or equal to 60 ml/min/1.73 m2 body surface area, 6 months or more post-transplant) and in 9 kidney donors. Sixteen patients had normal parathyroid function, 8 had hypercalcemic hyperparathyroidism and 9 had normocalcemic hyperparathyroidism; the latter were apparently resistant to the hypercalcemic actions of endogenous PTH, but the cause for this was not apparent. In all four subject groups, TmP/GFR was significantly and similarly lower (by 0.8-1.0 mg/dl) than predicted by multiple regression on age, sex, corrected plasma calcium and NcAMP (determined in 306 subjects spanning a wide range of parathyroid function) indicating a major PTH-independent mechanism for reducing phosphate reabsorption in the presence of a single kidney. In all four groups the contribution of this mechanism to the observed depression of TmP/GFR was substantially greater than the contribution of increased PTH secretion. In all groups, but more so in the recipients than in the donors, fasting urinary phosphate excretion/GFR was increased, so that fasting plasma phosphate, although reduced, did not accurately reflect the severity of the defect in phosphate reabsorption. We conclude that the dominant mechanism for the adaptive decrease in renal tubular phosphate transport in response to nephron reduction does not require the participation of PTH and is manifest in the presence of fasting hypophosphatemia.
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PMID:Reduced phosphate reabsorption unrelated to parathyroid hormone after renal transplantation: implications for the pathogenesis of hyperparathyroidism in chronic renal failure. 354 37

Dietary calcium (CA++) supplementation attenuates gentamicin nephrotoxicity in rats. It has been proposed that this protective effect results from the ability of Ca++ to interfere with gentamicin binding to renal cell membranes. However, calcium supplementation also suppresses parathyroid hormone (PTH) activity, which may affect gentamicin nephrotoxicity by altering renal brush border phospholipid composition or renal calcium handling. We therefore compared gentamicin nephrotoxicity in PTH-stimulated control rats and parathyroidectomized (PTX) rats. Although their pretreatment serum ionized calcium concentration was significantly higher (1.27 +/- 0.01 vs. 0.88 +/- 0.06 mmol/L; P less than 0.001), PTH-stimulated rats had higher peak renal cortical gentamicin concentrations (543 +/- 20 vs. 395 +/- 49 micrograms/gm; P less than 0.025) and serum creatinine concentrations (3.0 +/- 0.8 vs. 0.9 +/- 0.3 mg/dl; P less than 0.05). Structural injury and depression of renal cortical slice uptake of p-aminohippurate were also less severe in PTX rats. Gentamicin treatment also caused increased urinary Ca++ excretion in control rats (from 2.12 +/- 0.64 mumol/mg creatinine per day [pretreatment] to 16.86 +/- 2.07 mumol/mg creatinine per day; P less than 0.001) but not in PTX rats. Control rats ingesting chow containing a standard Ca++ content (1.2%) resembled PTX rats. These results indicate that PTH stimulation exacerbates gentamicin nephrotoxicity. Increased peak renal cortical gentamicin concentrations in PTH-stimulated rats may be caused by increased gentamicin transport across the brush border as a consequence of PTH-mediated alteration of plasma membrane phospholipid composition, turnover, or both.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of parathyroid hormone activity on gentamicin nephrotoxicity. 379 14

The behavior of membranes concerned with parathyroid hormone secretion was studied by electron microscopic morphometry in parathyroid cells of rats with temporarily reduced serum calcium concentration resulting from phosphate ion application and in rats with elevated serum calcium concentration following vitamin D3 administration. The phosphate ion application resulted in an increase of the cell surface area and a concomitant decrease of the surface area of the Golgi complex and secretory granules within 3 hours. After 3 hours, the cell surface area decreased, whereas the surface area of the Golgi complex and the secretory granules increased, and after 12 hours, the surface area of the rough endoplasmic reticulum also increased. In the vitamin D3-treated rats the surface area of the secretory granules increased, but the cell surface area had decreased by 24, 48, and 72 hours after application. These data suggest that parathyroid cells respond to a transient depression of the serum calcium concentration by an initial centrifugal membrane shift indicating enhanced exocytosis, followed by a centripedal membrane shift indicating enhanced endocytic retrieval of the plasma membrane. Later, membrane synthesis led to an increase of the membrane compartments concerned with parathyroid hormone secretion. Elevation of the serum calcium concentration following vitamin D3 treatment resulted in reduced release of parathyroid hormone by exocytosis and enhanced retrieval of plasma membranes by endocytosis. The fate of the retrieval plasma membrane remains unclear.
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PMID:Quantitative aspects of membrane behavior in rat parathyroid cells after depression or elevation of serum calcium. 388 31

Some patients with hypertriglyceridemia and acute pancreatitis have marked hypocalcemia and high levels of plasma free fatty acids (FFAs). This study tests the hypothesis that increased plasma FFAs can significantly reduce the calcium level in vivo, a phenomenon which is different from local formation of calcium soaps due to lipolysis of adipose tissue lipids. Free fatty acid elevation was induced in rats by the administration of heparin and by the infusion of triglycerides. The results show that, compared with controls, induction of elevated FFA (from 1.57 +/- 0.08 mEq/L to 5.64 +/- 0.35, mean +/- SEM) causes the concentration of calcium to fall rapidly (from 9.04 +/- 0.06 mg/dl to 8.42 +/- 0.10, p less than 0.001). There is a significant (p less than 0.001) positive correlation between spontaneous baseline concentration of FFA and the responsiveness of calcium concentration to FFA challenge. At near-normal levels of FFA there is a significant (p less than 0.001) correlation between the magnitude of increased FFA concentration and decreased calcium concentration. Additional studies in vivo and in vitro show that elevated plasma triglycerides per se did not interfere with measurement of calcium concentration; however, FFA-albumin complexes bind calcium and lower its measured value. These findings suggest that (a) changes in the concentration of FFA occurring spontaneously may affect measured serum calcium concentration; (b) the observed depression of serum calcium concentration may be due in part to intravascular sequestration of calcium by FFA, but increased flux of circulating calcium-FFA complexes into extravascular and intracellular sites may also be important; (c) the markedly increased FFA concentration in some patients with acute pancreatitis may contribute significantly to hypocalcemia and calcium flux in these patients. As parathyroid hormone secretion, function, or integrity may be impaired in pancreatitis, the depressant effect of FFA could be even greater in that disease than in this model.
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PMID:Depression of serum calcium by increased plasma free fatty acids in the rat: a mechanism for hypocalcemia in acute pancreatitis. 402 61

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