Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MCR and half-disappearance time of exogenously administered somatostatin have been measured during and after cessation of a constant infusion. Studies were performed on normal volunteers and patients with chronic liver disease and failure. Immunoreactive somatostatin was measured by a sensitive and specific RIA using an antiserum directed against the core of the molecule. Normal subjects had a mean MCR of 1949 +/- 250 ml/min (28.4 +/- 4.2 ml/min . kg BW) (mean +/- SEM), similar to values found in five patients with chronic liver disease. However, patients with chronic renal failure showed a highly significant (P less than 0.001) lowering of the MCR (501 +/- 32.7 ml/min or 7.8 +/- 0.6 ml/min . kg). The rate of disappearance of somatostatin after infusion was linear for 7-10 min, after which a much slower component was observed. In normal subjects, the t 1/2 of the first component varied from 1.1-3.0 min, in patients with liver disease it varied from 1.2-4.8 min, and in patients with chronic renal failure it varied from 2.6-4.9 min. Exogenously administered somatostatin is rapidly cleared in normal subjects and patients with chronic liver disease, but the MCR in end stage chronic renal failure is markedly lowered. The kidney may have a role in the metabolic clearance of exogenously administered somatostatin, or uremia may impair catabolism nonspecifically.
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PMID:Metabolic clearance and plasma half-disappearance time of exogenous somatostatin in man. 42 6

The metabolism of the synthetic progestin, [3H]medroxyprogesterone acetate (MPA), was studied in women using a single injection technique. Computer-implemented analysis was used to calculate the MCR (MCRMPA) and volume of distribution (VoMPA) from the steroid disappearance curve. The value of an objective curve-fitting technique was demonstrated. The effect of protocol design (number and frequency of samples) on these metabolic parameters was evaluated. The estimation of VoMPA was most sensitive to alterations of experimental design and biological variability, while MCR was less easily effected. The MCRMPA of 1668 +/- 146 (SEM) liters/day was lower than that for progesterone but higher than that of another synthetic steroid, dexamethasone. Treatment of women with MPA or aminoglutethimide, two drugs known to increase the rates of testosterone and dexamethasone metabolism, respectively, did not alter MCRMPA. From these observations we conclude 1) with the single injection technique it is difficult to estimate Vo of compounds such as MPA which are rapidly metabolized and 2) the MCRMPA was higher than expected and less susceptible to drug-induced changes than the clearance of other steroids.
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PMID:In vivo metabolism of progestins. V. The effect of protocol design on the estimated metabolic clearance rate and volume of distribution of medroxyprogesterone acetate in women. 42 26

It has been shown that despite an effect of minoxidil to increase PRA, plasma levels of aldosterone do not change. We observed similar findings in seven hypertensive patients undergoing treatment with minoxidil; PRA activity increased markedly, whereas the plasma aldosterone concentration showed no consistent change. The aldosterone MCRs in these patients increased by 41% in response to minoxidil, from 1110 +/- 91 to 1570 +/- 180 (SEM) liters/day; this appeared to explain why plasma aldosterone levels did not increase in parallel with renin activity. Hepatic blood flow (estimated from the clearance of indocyanine green) in a group of patients receiving minoxidil was greater than that in an otherwise comparable group (P less than 0.02). This increase in hepatic perfusion may, at least in part, have accounted for the increase in aldosterone MCR.
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PMID:Minoxidil increases aldosterone metabolic clearance in hypertensive patients. 51 74

Long-term specific tolerance to one haplotype class I plus minor antigen disparate renal allografts develops without exogenous immunosuppression in approximately 35% of miniature swine (n = 128). Previous studies have suggested that this phenomenon is related to limited class I-specific helper T cell activity as evidenced by the failure of antibody class switching in vivo and the ability of exogenous interleukin 2 to elicit antidonor responses in vitro. To determine whether tolerance could be broken by inducing antidonor reactivity with donor antigen and a source of T cell help, multiple skin grafts bearing donor class I plus third-party class II antigens were placed on tolerant animals. Skin grafts were placed at least 3 months after the kidney transplant, at which time all recipients had normal renal function as measured by blood urea nitrogen and serum creatinine. First-set rejection of skin grafts by SLAad and SLAdd hosts occurred in 11.8 +/- 1.1 days (mean +/- SEM, n = 6) and in 9.3 +/- 0.9 days (n = 4), respectively. Coincident with skin rejection, most animals developed a transient rise in BUN to 62 +/- 11 mg/dl (n = 10) and a similar rise in Cr to 4.9 +/- 1.2 mg/dl (n = 10), with normal levels returning in all animals within two weeks. Subsequent skin grafts with the same disparity did not undergo second-set rejection and did not induce BUN or Cr elevations. Prior to skin grafting, animals showed no antidonor activity in mixed lymphocyte reaction or cell-mediated lymphocytotoxicity assays. After two skin grafts, all animals developed donor-specific CML and secondary MLR responses, and additional skin grafts amplified this cellular immunity. Development of marked antidonor immunity without a break in tolerance suggested that either graft adaptation or local suppression might be involved in maintaining tolerance to class I MHC antigens. In preliminary studies, an immunized SLAad animal and an immunized SLAdd animal were retransplanted with kidneys MHC matched to their first allografts. In both cases, the second graft was accepted permanently without immunosuppression, suggesting that graft adaptation is not necessary for the maintenance of tolerance to renal allografts in miniature swine.
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PMID:The failure of skin grafting to break tolerance to class I-disparate renal allografts in miniature swine despite inducing marked antidonor cellular immunity. 175 67

Octreotide (Sandostatin), a potent and long-acting octapeptide analogue of somatostatin, exhibits variable metabolic effects in type 1 diabetes. We have postulated that interindividual variability in octreotide metabolism could be responsible in part for the differences in metabolic responses reported in previous clinical studies. To this end, we determined plasma levels and MCR of octreotide during 24-hour continuous SC infusion (low dose, 200 micrograms; high dose, 400 micrograms) in nine female, C peptide-negative patients with type 1 diabetes. The metabolic effects of the analogue were assessed by measuring serum glucose, free insulin, glucagon, GH, and PP levels before and at 1- to 2-hour intervals during each dose of the analogue or control (0.9% saline solution) infusion in a single-blind randomized manner. Mean daytime (0800-0000 hours) and bedtime (0000-0800 hours) serum glucose levels decreased significantly (p less than 0.05 to 0.02) during analogue therapy compared with control. Mean serum free insulin levels were significantly (p less than 0.02) greater during octreotide infusion compared with control, despite the similar daily insulin requirements. Both doses of the analogue effectively suppressed 24-hour GH by 50%, glucagon by 50%, and PP by 80%. Steady-state octreotide levels varied considerably among patients (low, mean +/- SEM), 1000 +/- 101, range 638 to 1375 pg/ml; high, mean 1940 +/- 147, range 1032 to 2462 pg/ml). Although mean MCR values were similar with both doses, we observed greater interindividual variability (low, mean 2.45 +/- 0.30, range 1.31 to 3.78 ml/kg/min; high, mean 2.36 +/- 0.19, range 1.68 to 3.48 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Continuous subcutaneous octreotide infusion: dose-response relationships between metabolic effects and octreotide clearance in patients with insulin-dependent (type 1) diabetes. 206 44

We injected a highly purified preparation of the beta-core molecule, a fragment of hCG beta excreted in pregnancy urine, into five men and three women to determine its kinetic parameters, MCR, and urinary clearance. The beta-core molecule was distributed in an initial volume [1950 +/- 156 (mean +/- SEM) mL/m2 body surface area] approximately equal to the estimated plasma volume. Its disappearance was multiexponential on a semilogarithmic plot, with a rapid phase t1/2 of 3.5 +/- 0.7 min and a slow phase t1/2 of 22.4 +/- 4.2 min. The transit time (the mean time spent by a molecule of beta-core in transit) was 20.6 +/- 2.1 min. The MCR was 192.0 +/- 8.0 mL/min.m2 body surface area. About 5% of the injected dose of beta-core was excreted into the urine in the first 30 min after injection, and low levels of excretion persisted for up to 7 days. The urinary clearance rate of beta-core was 13.7 +/- 1.4 mL/min.m2, accounting for about 8% of the elimination of beta-core from the plasma. The beta-core immunoreactivity in serum and urine was characterized by gel filtration and three independent RIA systems to show that its properties were indistinguishable from those of the injected beta-core. Serum levels of beta-core in pregnant women were less than 0.2 ng/mL, while the amounts excreted in their urine were as much as 5 mg/day. Based on these clearance parameters of beta-core in normal subjects, less than 0.2% of the beta-core excreted in pregnancy urine is derived by urinary clearance of plasma beta-core. Therefore, more than 99% of the beta-core excreted in pregnancy urine is derived from beta-core in a compartment separate from plasma. In particular, these data indicate that there is relatively little placental secretion of beta-core into plasma and that placental secretion does not account for the vast majority of beta-core in pregnancy urine. These findings are consistent with previous data that point to renal parenchymal degradation of hCG and hCG beta as the major source of urinary beta-core in pregnancy.
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PMID:Metabolic clearance rate and urinary clearance of purified beta-core. 247 63

Alterations in the autologous mixed lymphocyte reaction (autologous MLR) have been reported in many autoimmune diseases and in diseases with a derangement of T regulatory function. We have studied autologous MLR in 10 patients with idiopathic autoimmune hemolytic anemia (IAHA). All patients had decreased autologous MLR which averaged 4,106 +/- 1,332 cpm (SEM) compared to 12,153 +/- 4,166 cpm for simultaneously studied controls. A marked decrease in phytohemagglutinin response and an imbalance of T-cell subsets were also observed. These findings suggest a possible abnormality of T immunoregulatory function in IAHA patients.
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PMID:Deficiency of autologous mixed lymphocyte reaction in patients with idiopathic autoimmune hemolytic anemia. 293 54

The effect of posture on plasma atrial natriuretic peptide (ANP) levels during a constant iv infusion of the 28-amino acid polypeptide was investigated in 8 normal men. alpha-Human ANP was infused at a constant rate of 0.5 micrograms/min (162 pmol/min) while the men were supine, then erect, and finally when supine again. Plasma ANP levels rose from 10.9 +/- 1.6 (+/- SEM) to 33.3 +/- 2.4 pmol/L after 60 min of constant infusion with the men in the supine position. On standing, plasma ANP increased further to 40.6 +/- 3.4 pmol/L, then fell to 32.2 +/- 2.7 pmol/L with resumption of supine posture. The calculated MCR of ANP fell from a mean of 7.7 to 5.7 L/min on standing, but rose again to 7.6 L/min upon lying down. We conclude that body posture has a significant effect on the rate of clearance of ANP from plasma.
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PMID:Effect of posture on clearance of atrial natriuretic peptide from plasma. 296 Jun 88

Hyperprolactinemic patients may have increases in plasma dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS). We examined the effect of lowering serum PRL with bromocriptine or pituitary surgery on the serum concentrations of adrenal androgens and on the production rate (PR) and MCR of DHAS in eight hyperprolactinemic women (HP). We also examined the effect of bromocriptine therapy on adrenal androgens in five normal men. Serum DHAS was elevated in HP compared to normal women (mean +/- SEM, 254 +/- 28 vs. 182 +/- 13 microgram/dl; P less than 0.04). Serum DHA and androstenedione (delta 4) in HP were not significantly different from normal. Serum PRL fell from 160 +/- 16 to 37 +/- 9 ng/ml during or after treatment. Mean 24-h serum DHAS fell from 198 +/- 30 to 106 +/- 17 micrograms/dl (P less than 0.001) with treatment, without a change in the mean 24-h serum cortisol concentration (6.2 +/- 0.4 vs. 6.6 +/- 0.4 micrograms/dl). Thus, the DHAS to cortisol (DHAS/F) ratio fell significantly (32 +/- 5 to 17 +/- 4; P less than 0.001). This was also true of the DHAS/F ratio during ACTH stimulation (8 +/- 1 to 6 +/- 1; P less than 0.02). Similar changes were found in basal and ACTH-stimulated DHA/F ratios, whereas the basal and ACTH-stimulated delta 4/F ratios did not change significantly with treatment. Treatment lowered the PR of DHAS from 27 +/- 5 to 17 +/- 3 mg/24 h (P less than 0.03) and increased the DHAS MCR from 16 +/- 2 to 21 +/- 3 liters/24 h (P less than 0.01). Bromocriptine treatment of normal men lowered serum PRL from 15 +/- 2 to less than 2.5 ng/ml. There were no significant changes in the basal and ACTH-stimulated serum DHAS/F, DHA/F, or delta 4/F ratios or DHAS PR and MCR during bromocriptine therapy. The failure of bromocriptine to significantly alter these steroids in normal men suggests that bromocriptine was not directly responsible for the changes in HP treated with this drug. A mechanism for the increased PR of DHAS in HP was sought by examining the serum concentrations of the steroid biosynthetic intermediates relevant to DHAS production. Lowering serum PRL was associated with a decrease in basal and ACTH-stimulated 17-hydroxypregnenolone/17-hydroxyprogesterone and DHA/delta 4 ratios, suggesting an increase in 3 beta-hydroxysteroid dehydrogenase/delta 4,5-isomerase activity. However, increased gonadal secretion of the delta 4-steroids may have occurred with the fall in serum PRL.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effect of serum prolactin on plasma adrenal androgens and the production and metabolic clearance rate of dehydroepiandrosterone sulfate in normal and hyperprolactinemic subjects. 299 77

We have determined metabolic parameters for androstenedione (A) in chronically catheterized late gestation (day 130) sheep fetuses. The MCR (MCRA) was 3210 +/- 229 (SEM, n = 12) ml/min, the fetal arterial whole blood concentration of A [A] was 65 +/- 5 pg/ml, and the blood production rate (PRA) was 204 +/- 20 ng/min. Pulsatile administration of ACTH in amounts that raised fetal arterial plasma cortisol concentrations by 5- to 7-fold increased [A] to 154 +/- 20 pg/ml and PRA to 471 +/- 31 ng/min with no change in MCRA. In the presence of metopirone to block fetal adrenal cortisol output, ACTH treatment still provoked elevations in [A] (to 198 +/- 23 pg/ml) and PRA (539 +/- 158 ng/min), without altering MCRA. The major radiolabeled product in blood of infused [3H]A was [3H]testosterone; smaller amounts of phenolic steroids were formed. Extensive metabolism of [3H]A occurred in whole blood in vitro. The major product was [3H]testosterone; the 17-oxidoreductase activity was associated with the red blood cells. Umbilical vein [A] was greater than umbilical artery [A]; ACTH treatment increased [A] in both vessels. Concomitant metopirone abolished the arteriovenous difference by eliminating the ACTH-induced increase in venous [A], although arterial [A] rose significantly. The venous [A] and the arteriovenous gradient were restored with exogenous glucocorticoid treatment to the fetus. Collagenase-dispersed fetal adrenal cells secreted A. Adrenal cells from fetuses pretreated with ACTH in vivo had higher basal and ACTH-induced output of A in vitro than cells from fetuses pretreated with saline in vivo. We conclude that the MCRA in fetal sheep is extremely high, in part due to conversion of A to testosterone in fetal blood. The elevated PRA after ACTH plus metopirone and the lack of an umbilical arteriovenous gradient of [A] in this, but not other groups of fetuses, suggests a source of A production independent of the cortisol-induced changes in the placenta. Direct evidence is provided for fetal adrenal secretion of A which is enhanced by ACTH pretreatment of the fetus in vivo and for the utilization of circulating A in the fetus as a precursor for estrogen in both fetal and maternal compartments.
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PMID:Androstenedione metabolism in the late gestation sheep fetus. 300 Jul 49


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