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 cause of pathological hyperprolactinemia (PHP) is not known, although it has been postulated that lactotroph refractoriness to dopamine (DA) is an important factor. We, therefore, studied PRL suppressibility in response to iv DA administered in a dose designed to achieve peripheral plasma DA concentrations in the range reported in rat pituitary portal plasma. Nine normal subjects and 14 patients (8 with probable microadenomas and 6 with macroadenomas) with PHP were studied during a 4-h infusion of 0.5 micrograms/kg X min DA. Serum PRL levels decreased in normal subjects to 18 +/- 3% (mean +/- SEM) of initial basal levels, not significantly different from the fall to 22 +/- 2% of basal levels found in patients with PHP. Maximal PRL suppression in patients with probable microadenomas (21 +/- 2%) was not significantly different from that in those with macroadenomas (22.8 +/- 2.0%). Upon cessation of DA infusion, there was a rapid rebound in PRL release, which was significantly greater (P less than 0.05) in patients (155 +/- 15%) than in normal subjects (118 +/- 13%). Plasma DA levels were measured by gas chromatography/mass spectroscopy and were significantly higher (P less than 0.05) in patients than in normal subjects during the infusion. The MCR for DA in normal subjects (12.5 +/- 2.8 liters/kg X h) was significantly greater (P less than 0.005) than that in patients (6.2 +/- 0.5 liters/kg X h). The data show that the release of PRL in patients with PHP is not refractory to physiological concentrations of DA, but that there is an abnormality of peripheral DA metabolism in these patients. We conclude that the development of PHP is unlikely to be due to insensitivity of lactotrophs to endogenous DA and that patients with PHP have a systemic disturbance of DA metabolism.
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PMID:Dopamine infusion studies in patients with pathological hyperprolactinemia: evidence of normal prolactin suppressibility but abnormal dopamine metabolism. 668 78

Oxytocin (OT) was measured by RIA in plasma of women during hypocontractile labor before and during graded doses of iv infused synthetic OT. Based upon in vitro studies of recovery of OT from pregnancy plasma, blood was collected into heparinized tubes which were kept at 4 C. The addition of EDTA and phenanthrolene to an aliquot of each sample resulted in measured levels of OT in plasma that correlated closely with levels measured in the absence of these reagents (r2 = 0.86). Comparison of OT levels in plasma of normal individuals determined in the presence and absence of these reagents also yielded a high degree of linear correlation (r2 = 0.97). The mean level of OT in 11 women during hypocontractile labor before the infusion of OT was 1.01 +/- 0.31 (+/- SEM) microU/ml. There was a linear correlation between the dose of OT infused and the level of OT in plasma with infused doses of OT between 1 and 4 mU/min (r2 = 0.99). The time of onset of adequate uterine contractility was recorded by on-line computer analysis, and the level of OT in plasma obtained simultaneously was variable among the women. The mean OT MCR in these women was 17.4 +/- 9.2 (+/- SEM) ml/kg X min, similar to the MCR in normal men (17.6 +/- 2.1 ml/kg X min). Levels and pharmacokinetics of OT during hypocontractile labor were similar to those in nonpregnant individuals and women in late pregnancy. The variability in OT concentrations at the time of adequate uterine contractility suggests that individual myometrial sensitivity is an important determinant of the response to administered OT in humans.
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PMID:Studies of oxytocin in plasma of women during hypocontractile labor. 669 37

Neurotensin (NT) is a 13 amino acid peptide found predominantly in the ileum and it is released into the circulation by a meal. Much of the circulating NT consists of N terminal fragments which have no known biological activity. However, the sites and rates of NT metabolism are not known. In the present study the MCR and half-disappearance time of NT were estimated by infusing NT(1-13) into 10 normal subjects. The role of the kidney was assessed by studies in patients with chronic renal failure (CRF). The nature of the metabolites was characterized using region specific antisera and high pressure liquid chromatography (HPLC). The plasma pancreatic polypeptide response to the NT infusion was also measured. The NT MCR in normal subjects was 88 +/- 25 (SEM) ml/min X kg measured with the C terminal antiserum but only 9.9 +/- 0.8 ml/min X kg measured with the N terminal antiserum, a result consistent with the presence of long lasting N terminal fragments. HPLC of the plasma at equilibrium established that only 20% of the immunoreactivity was present as NT(1-13), with the majority as NT(1-8). No C terminal fragment were detected. Similarly, incubation of NT(1-13), 1-8, and 8-13 in plasma in vitro showed that N terminal fragments were stable in plasma, whereas C terminal fragments were completely metabolized. In patients with CRF, basal plasma NT (measured with the C terminal antisera) was significantly elevated and C terminal MCR was reduced by 82% and N terminal MCR by 32%. Thus the major effect of CRF was on the initial degradation of NT(1-13) to N terminal fragments. HPLC showed that over 60% of the NT was present as NT(1-13). In vitro degradation of NT was also slowed in CRF plasma. The increased proportion of intact biologically active NT in the circulation of the CRF patients could also explain the greater increase in pancreatic polypeptide levels during the NT(1-13) infusion. These studies have established that the metabolism of NT is influenced by the kidney and that the presence of predominantly N terminal fragments of NT in the peripheral circulation of normal subjects can be explained by a combination of renal and extrarenal factors.
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PMID:Metabolism of neurotensin and pancreatic polypeptide in man: role of the kidney and plasma factors. 670 91

Gastrin-releasing peptide (GRP) was infused at two dose levels [GRP I (0-30 min): bolus dose of 1.41 pmol kg-1, followed by 0.12 pmol kg-1 min-1; GRP II (30-60 min): bolus dose of 5.67 pmol kg-1, followed by 1.50 pmol kg-1 min-1] to six normal men to study the pharmacokinetics of GRP using a newly developed RIA and the effect of GRP on gastro-entero-pancreatic hormones and gastric acid secretion. The half-life of disappearance of GRP was 2.8 +/- 0.4 min (+/- SEM). The MCR and the apparent space of distribution were 33.0 +/- 4.0 ml kg-1 min-1 and 133 +/- 31 ml kg-1, respectively. GRP stimulated the secretion of gastrin, pancreatic polypeptide, insulin, glucagon, and glucose-dependent insulinotropic polypeptide in a dose-dependent manner. Gastric acid secretion was stimulated 15 min after the increase in gastrin secretion, suggesting that GRP stimulated gastric acid secretion via release of gastrin. GRP had no significant effect on the secretion of enteroglucagon or neurotensin. In the mammalian gastrointestinal tract, GRP is localized exclusively to nerve tissue. This fact and its potent effects demonstrated here make it a likely candidate for peptidergic nervous control of gastrointestinal function.
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PMID:Gastrin-releasing peptide: pharmacokinetics and effects on gastro-entero-pancreatic hormones and gastric secretion in normal men. 673 5

Synthetic neurotensin was infused into five healthy subjects at a mean dose of 2.3 pmol/kg . min for 30 min, producing a rise in plasma neurotensin concentrations, measured by RIA of 104 +/- 10 (mean +/- SEM) pmol/liter. The mean disappearance half-time on stopping the infusion was 3.8 +/- 0.2 min. The MCR was 16 +/- 1 ml/kg . min, and the apparent space of distribution was 88 +/- 6 ml/kg. During the neurotensin infusions, plasma pancreatic polypeptide rose by 145 +/- 54 pmol/liter. In contrast to results in experimental animals, there was no significant change in the pulse or blood pressure of the subjects or any significant change in blood glucose or plasma concentrations of insulin, glucagon, gastric inhibitory peptide, gastrin, motilin, or vasoactive intestinal peptide. Similarly, there was no change in plasma concentrations of TSH, GH, PRL, LH, and FSH.
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PMID:Neurotensin infusion in man: pharmacokinetics and effect on gastrointestinal and pituitary hormones. 700 47

A continuous infusion technique of either [3H]oestradiol-17 beta (E2) or unlabelled E2 was used to investigate suggested differences in the metabolic clearance rate of oestradiol-17 beta (MCR-E2) in immature and peripubertal female pigs. Using the isotope infusion technique, the following values were obtained: 60 day old gilts; MCR-E2 = 2133 +/- 274 (mean +/- SEM) ml/min, MCR-E2/kg BW = 116 +/- 14.5 ml/min kg, and conversion ratio (CR) of E2 to oestrone (E1) = 31.6 +/- 3.7%. The respective values for 160 day old gilts were: MCR-E2 = 3027 +/- 340, MCR-E2/kg BW = 48.5 +/- 4.82, and CR = 15.9 +/- 2.12. Except for a significant difference in the weight related MCR-E2 data for the 60 day old group, similar values were found following infusion of unlabelled E2. The percentage of radioactivity extractable with ether from plasma was 22.6 +/- 3.0% and 27.2 +/- 2.0%. Fifty-seven and 66% of total radioactivity infused was recovered in the urine within 12 h in 60 and 160 day old gilts, respectively. There was no difference in the percentage binding of E2 to plasma proteins as determined by equilibrium dialysis (80%). It is concluded that in addition to an activation of ovarian steroido-genesis during puberty, a gradual maturational decrease in the MCR-E2/kg VW might play a role in raising plasma E2 concentrations and thus in constituting an effective oestrogen feedback signal, which results in the first pre-ovulatory LH-surge.
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PMID:A comparison of metabolic clearance rates of oestradiol-17 beta in immature and peripubertal female pigs and possible implications for the onset of puberty. 712 81

The metabolism of androstenedione (A) by the placenta in late pregnancy and the early puerperium was studied. The metabolic clearance rate of A (MCR-A) was increased in pregnant women, 2,825 +/- 207 L/24 hr (mean +/- SEM), compared to 2,020 +/- 140 L/24 hr in nonpregnant women of similar body weight. The immediate puerperal MCR-A was 2,538 +/- 50 L/24 hr. Therefore, approximately 10% of maternal plasma A was cleared by the placenta. In the latter half of pregnancy, the extent of conversion of maternal plasma A through estradiol formation, (rho)AE2, was increased, whereas in the immediate puerperium it was normal, 0.018. Moreover, 90% of aromatase activity was attributed to the placenta in late pregnancy. From these data, we computed that the placental clearance rate of A through estradiol (PCAE2) from whole blood was 497 +/- 41 ml/min in women with a single fetus and 691 +/- 102 ml/min in women with twin fetuses. Thus, it appears that the PCAE2 is a sensitive index of maternal-placental perfusion.
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PMID:Placental clearance rate of maternal plasma androstenedione through placental estradiol formation: an indirect method of assessing uteroplacental blood flow. 731 14

To investigate the interaction between dopamine and aldosterone in man, either the dopamine antagonist, metoclopramide [methoxy-2-chloro-5-procainamide (M)], or a placebo was given by an iv bolus in a random, double blind fashion to nine supine volunteers on a hospital diet (mean urinary sodium excretion, 135 +/- 17 vs. 145 +/- 26 meq/24 h; P = NS). After M (10 mg), plasma aldosterone (PA) rose from 6.4 +/- 1.1 to 14.0 +/- 2.2 (SEM) ng/dl (P less than 0.01) within 15 min. PRA, potassium, and cortisol were unchanged. PRL increased 10-fold, but individual increments in PA and PRL did not correlate significantly. Oral M (10 mg) produced a rise in PA in only two of five volunteers. To determine whether the increase in PA was due to the dopamine antagonist properties of M, the iv study was repeated in four of the volunteers during an ongoing dopamine infusion. The integrated incremental change in PA during the hour after M administration was markedly blunted (399 +/- 56 vs. 69 +/- 32 ng/dl.min; P less than 0.05), and the PRL response was totally abolished. Assuming no major effects of M on the MCR of aldosterone, these data suggest a tonic inhibitory influence of dopamine on aldosterone secretion.
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PMID:Tonic dopaminergic suppression of plasma aldosterone. 738 Sep 93

To investigate whether chronic endogenous hypercortisolism might alter adrenomedullary phenylethanolamine N-methyltransferase activity, we measured epinephrine/norepinephrine (E/NE) ratios in the adrenal venous blood of 8 patients undergoing surgery for Cushing's syndrome and in 12 control subjects undergoing surgery for left kidney diseases. To investigate the adrenomedullary secretory activity in Cushing's syndrome, we measured basal E plasma levels in 24 patients and 32 age- and sex-matched normal control subjects, and we evaluated the adrenomedullary response to glucagon in 9 patients and in 22 age- and sex-matched normal subjects. Last, to clarify whether chronic endogenous hypercortisolism might modify E plasma levels through a modification of E metabolism, we measured the E MCR in four patients and four age-matched controls. Mean (+/- SEM) E/NE ratio in adrenal venous blood was similar in patients with Cushing's syndrome (4.61 +/- 0.78) and in the control group (4.71 +/- 0.74). Mean (+/- SEM) basal plasma E was significantly lower in patients with Cushing's syndrome (98.2 +/- 10.9 vs. 184 +/- 25.1 pmol/L, P < 0.01) than in the control group. Similarly, plasma NE also was reduced (0.75 +/- 0.09 vs. 1.10 +/- 0.07 nmol/L, P < 0.01). In patients with Cushing's syndrome the E response to glucagon was significantly reduced (P < 0.01). E MCR was almost identical in patients with Cushing's syndrome (1.48 +/- 0.10 L/min.m2) and in control subjects (1.51 +/- 0.10 L/min.m2). Our data demonstrate that: 1) chronic endogenous hypercortisolism is not able to change adrenomedullary phenylethanolamine N-methyltransferase activity and therefore the quality of adrenomedullary secretion; and 2) chronic endogenous hypercortisolism causes a decrease in basal and stimulated adrenomedullary activity without altering E MCR significantly. Therefore the adrenal medulla does not seem to play a pathogenetic role in the hypertension of Cushing's syndrome.
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PMID:Adrenal medulla secretion in Cushing's syndrome. 820 Sep 34

IFN-gamma is a potent pro-inflammatory cytokine involved in the immunologic rejection of transplanted organs. Having previously demonstrated differential suppressive effects of methylprednisolone (MP), prednisolone (P) and cyclosporine (CsA) on dialysis patients' lymphocyte proliferative responses to phytohaemagglutinin (PHA), we studied the effects of these drugs on dialysis patients' lymphocyte IFN-gamma production during mitogenic and allogeneic (MLR) stimulation. The mean +/- SEM 50% inhibitory concentration (ng/ml) on cell proliferation was significantly lower for MP than P in PHA-stimulated haemodialysis (HD) patients' (35 +/- 7 vs 152 +/- 25, P < 0.001) and peritoneal dialysis (PD) patients' (35 +/- 11 vs 134 +/- 33, P = 0.001) cultures and in HD patients' MLR cultures (15 +/- 3 vs 48 +/- 9, P < 0.001). The mean +/- SEM fractional responses (PHA or MLR + drug/PHA or MLR) in culture supernatant IFN-gamma concentrations were significantly lower with 10(-7) M concentrations of MP than P in HD (0.19 +/- 0.05 vs 0.31 +/- 0.06, P = 0.01) and PD (0.30 +/- 0.11 vs 0.46 +/- 0.11, P < 0.05) PHA cultures and in HD MLR cultures (0.15 +/- 0.04 vs 0.28 +/- 0.07, P = 0.01). CsA (400 ng/ml) alone not only caused less than 50% inhibition of IFN-gamma production in 15/27 HD PHA, 6/14 PD PHA and 4/13 HD MLR cultures, but actually stimulated it in 9 HD and 5 PD PHA cultures. The results suggest that: (1) MP has greater immunosuppressive potential than P for renal transplant recipients; (2) the stimulation of IFN-gamma by CsA in some patients could be harmful in patients with initial allograft dysfunction; and (3) pre-transplant in-vitro assessment of recipients' PBMC responsiveness to glucocorticoids and CsA may help individualize the post-transplant immunosuppressive regimen.
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PMID:Differential suppression of dialysis patients' lymphocyte IFN-gamma production by glucocorticoids and cyclosporine. 898 Aug 83


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