Effects of peptide YY on CCK/CCK antagonist interactions in cerulein-induced pancreatic injury.
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Amylases↗
Biomedical subjects
M Rudnicki
Publications and source records attributed to M Rudnicki.
Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis.
The four myogenic basic helix-loop-helix proteins, MyoD, myogenin, Myf-5, and MRF4, can each activate skeletal muscle differentiation when introduced into nonmuscle cells. During embryogenesis, each of these genes is expressed in a unique but overlapping pattern in skeletal muscle precursors and their descendants. Gene knockout experiments have shown that MyoD and Myf-5 play seemingly redundant roles in the generation of myoblasts. However, the role of either of these genes during differentiation in vivo has not been determined. In contrast, a myogenin-null mutation blocks differentiation and results in a dramatic decrease in muscle fiber formation, yet the role of myogenin in the generation or maintenance of myoblast populations is not known. Because myogenin possesses the same myogenic activity as MyoD and Myf-5 in vitro and the expression patterns of these three genes overlap in vivo, we sought to determine if myogenin shares certain functions with either MyoD or Myf-5 in vivo. We therefore generated mice with double homozygous null mutations in the genes encoding MyoD and myogenin or Myf-5 and myogenin. These mice showed embryonic and perinatal phenotypes characteristic of the combined defects observed in mice mutant for each gene alone. As shown by histological analysis and expression of muscle-specific genes, the numbers of undifferentiated myoblasts and residual myofibers were comparable between myogenin-mutant homozygotes and the double-mutant homozygotes. Myoblasts isolated from neonates of the combined mutant genotypes underwent myogenesis in tissue culture, indicating that no more than two of the four myogenic factors are required to support muscle differentiation. These results demonstrate that the functions of myogenin do not overlap with those of MyoD or Myf-5 and support the view that myogenin acts in a genetic pathway downstream of MyoD and Myf-5.
Animals↗
Collagen derived serum markers in carcinoma of the prostate.
Three new collagen markers deriving from the collagenous matrix, e.g. carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), and aminoterminal propeptide of type III procollagen (PIIINP) were used for the diagnose of prostatic bone metastases. Blood samples were obtained prior to biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial available RIAs and PSA by IRMA. Serum PSA was increased in patients with local prostatic cancer compared with patients with hyperplasia (p < 0.05). The level of PIIINP, ICTP, and PICP did not differ between these two groups. In patients with metastatic prostatic cancer all five markers were increased compared to the level measured in patients with localized cancer (p < 0.0001). All variables showed a significant positive relationship with alkaline phosphatase. The sensitivity ranged from 0.53 to 0.62 and specificity from 0.91 to 0.95. The sensitivity for alkaline phosphatase and PSA was 0.69 and 0.66 and specificity 0.91 and 0.68, respectively.
Aged↗
Lack of relationship between actual ionized calcium and pH in umbilical cord blood.
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Calcium↗
Magnesium supplementation in pregnancy-induced hypertension and preeclampsia.
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Administration, Oral↗
Effect of oral calcium on noninvasive indices of bone formation and bone mass in hemodialysis patients: a randomized double-blind placebo-controlled study.
The purpose of this study was to evaluate the effect of high-dose oral calcium on biochemical indices of bone formation, bone bisphosphonate clearance (BBC) and bone mineral content (BMC) of the distal forearm in patients undergoing hemodialysis. Eighteen patients agreed to participate and were randomized in a double-blind manner to receive either 2 g elemental calcium/day (n = 9) or placebo (n = 9) for 6 months. Previous treatment with aluminum-containing phosphate binders was continued unchanged throughout the study. In the placebo group, serum alkaline phosphatase and osteocalcin tended to increase by 8.0 and 10.2%, respectively, while BBC changed significantly by 49.5% (p < 0.05). In the calcium group the opposite was observed with small decreases in alakline phosphatase and osteocalcin by 8.2 and 11.0%, respectively, and no change in BBC. BMC decreased by 5.0% in the placebo group, but increased by 5.2% in the calcium group, resulting in a difference of 10.2% (p < 0.05). The present study demonstrates that high-dose oral calcium tends to reduce bone turnover and seems able to prevent bone loss in hemodialyzed patients.
Administration, Oral↗
Long-term oral calcium supplementation reduces diastolic blood pressure in end stage renal disease. A randomized, double-blind, placebo controlled study.
Previous studies suggest that oral calcium supply reduces blood pressure in patients with mild to moderate hypertension. The aim of this study was to determine whether oral calcium supply reduces blood pressure in patients undergoing haemodialysis. The study was randomized, double-blind, and placebo controlled. Eleven patients received two grams of calcium per day and 12 patients received placebo. Three patients (one from the calcium group and two from the placebo group) dropped out within the first month. The groups were comparable at inclusion regarding blood pressure, weight, and serum values. Blood pressure measurements were auscultatory with a mercury manometer and diastolic blood pressure was measured as Korotkoff phase V. At inclusion a significant positive correlation between serum phosphate and blood pressure was found. After a study period of six months a significant reduction in diastolic blood pressure was found between the two groups (p < 0.05), but no difference was found in systolic blood pressure. The reduction in diastolic blood pressure was 6.9 mmHg of the pretreatment level in the calcium group. In conclusion, the treatment of secondary hyperparathyroidism with oral calcium gives good benefits in the regulation of diastolic blood pressure. A well controlled phosphate homeostasis may also be of importance for the control of blood pressure in haemodialysis patients.
Administration, Oral↗
Calcium, magnesium, and free fatty acids in the formation of gallstones: a nested case-control study.
In a nested case-control study, calcium status was assessed by measurements of serum total calcium, magnesium, phosphate, ionized calcium, parathyroid hormone, albumin, total CO2 (bicarbonate), and free fatty acids in relation to gallstone formation. The subjects were recruited from a cohort study (n = 4,581) on the epidemiology of gallstones in Denmark. The cohort was examined with ultrasonography twice, in 1983 and 1988; 63 subjects developed gallstones, and among those who did not, 122 were randomly selected as controls. Subjects with gallstones had significantly increased serum concentrations of total calcium, magnesium, and bicarbonate as compared with normal subjects. The difference was only observed in women. Age, body mass index, alcohol consumption, and smoking did not influence the results when included as covariables in a logistic regression analysis. Multivariate analysis showed increased concentrations of magnesium, bicarbonate, and parathyroid hormone to be significantly associated with gallstone disease in women. No significant association was observed between gallstone disease and serum variables in men.
Bicarbonates↗
Peptide YY ameliorates cerulein-induced pancreatic injury in the rat.
Peptide YY (PYY), a known inhibitor of both pancreatic secretion and the release of cholecystokinin (CCK), may play a role in the pathophysiology of acute pancreatitis (AP). Supramaximal stimulation of the pancreas with CCK, or its analogue cerulein, induces edematous AP. We previously documented significant decreases in plasma PYY in sodium taurocholate-induced AP in the anesthetized pig, with exogenous PYY suppressing plasma amylase activity. We hypothesized that PYY may ameliorate cerulein-induced pancreatic injury in a conscious animal model. Thirty-two male Sprague-Dawley rats underwent chronic cannulation of the jugular vein and carotid artery for drug infusion and blood sampling. The animals were allowed to recover from anesthesia for a minimum of 16 hours, after which they were randomized to one of four (n = 8) treatment groups (cerulein 10 micrograms/kg/h, PYY 400 pmol/kg/h, cerulein+PYY, and control-saline 2 mL/kg/h). All treatments were administered by intravenous infusion over the first 6 hours of the experiment. Blood samples were taken prior to infusion and at 1, 3, 6, 9, and 24 hours into the study; the rats were then killed and the pancreata removed for weighing and histologic examination. All pancreatic specimens were graded in a blinded fashion for vacuolization, edema, inflammation, and necrosis. The mean basal plasma amylase level for all animals was 1,171 +/- 100 U/L and was not significantly different between groups. Infusion of cerulein resulted in significant increases in plasma amylase levels at 3, 6, 9, and 24 hours (4,827 +/- 1,022 U/L at 24 hours). In the group receiving both cerulein and PYY, the hyperamylasemia was attenuated with a return to basal values at 24 hours (1,206 +/- 103 U/L). There was significant pancreatic weight gain (1.99 +/- 0.07 g versus 1.03 +/- 0.07 g) and a worsened histologic picture in cerulein-treated animals compared with control animals (worsened edema, necrosis, and vacuolization). The addition of PYY to cerulein resulted in significantly lower pancreatic weight (1.27 +/- 0.11 g) than in the non-PYY-treated rats receiving cerulein. Pancreatic weight was not significantly different in this group compared with the control group. In addition, pancreatic histologic findings were significantly improved in those rats receiving PYY (decreased vacuolization and necrosis). Amylase levels, pancreatic weight, and morphologic findings were not significantly changed compared with basal values in the control or PYY alone treated groups. e conclude that as an inhibitor of pancreatic exocrine secretion, PYY ameliorates cerulein-induced pancreatic injury in the conscious rat.
Amylases↗
Effects of age, sex, season and diet on serum ionized calcium, parathyroid hormone and vitamin D in a random population.
OBJECTIVES: To study the influence of age, sex, season and diet on calcium status in normal subjects. DESIGN: A random population study. Setting. Institutional clinic for large population studies. SUBJECTS: The subjects were drawn randomly from the Danish Civil Registration System and represented a random sample of the background population in the area. The sample comprised 127 subjects (54 men and 73 women, aged 35-65 years). MAIN OUTCOME MEASURES: The effects of age, sex, season and diet on parathyroid hormone (PTH),1,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25-OHD). RESULTS: There was no statistical significant difference for the serum concentrations of ionized calcium, PTH, 1,25(OH)2D and 25-OHD between the two sexes, nor any influence by age in either sex, in contrast to serum phosphate, which declined significantly in men (P < 0.05), but tended to increase in women. Serum PTH (P < 0.009) showed seasonal fluctuations, whereas serum concentrations of 1,25(OH)2D, 25-OHD, ionized calcium, phosphate and magnesium remained stable throughout the year. Dietary intake of calcium and vitamin D were not related to any serum variables. CONCLUSIONS: In healthy subjects differences between the two sexes exist regarding phosphate metabolism. Serum PTH shows seasonal fluctuations.
Adult↗
Oral calcium effectively reduces parathyroid hormone levels in hemodialysis patients: a randomized double-blind placebo-controlled study.
The objective of this study was to elucidate the effect of oral calcium supplement upon the severity of secondary hyperparathyroidism and hyperphosphatemia in patients undergoing hemodialysis. Twenty-three accepted to participate and were randomly allocated to receive in a double-blind manner either 2 g elemental calcium per day (n = 12) or placebo (n = 11) for 6 months. Three patients dropped out leaving 10 patients in each group. In the calcium group serum ionized calcium increased significantly during the 1st month from 1.15 +/- 0.02 to 1.29 +/- 0.04 mmol/l (mean +/- SE) and was then stabilized at an average of 1.26 +/- 0.02 mmol/l for the remaining 5 months. Serum intact parathyroid hormone (PTH) decreased in average by 54% within the 1st month and remained at that level for the following months. Hyperphosphatemia remained stable throughout. On the contrary, in the placebo group, serum concentrations of ionized calcium and intact PTH remained unchanged, while serum phosphate increased significantly. The present study demonstrates that oral calcium reduces secondary hyperparathyroidism and prevents the progression of hyperphosphatemia in patients undergoing hemodialysis.
Adult↗
Serum ionized calcium, parathyroid hormone and phosphate in uremic patients during and between hemodialysis.
The serum concentrations of actual ionized calcium (at actual pH), adjusted ionized calcium (at pH 7.4), pH, intact parathyroid hormone (PTH) and phosphate were studied in ten patients during and between two hemodialysis sessions using a dialysate containing 1.66 mmol/l of calcium. Actual ionized calcium and adjusted ionized calcium increased during hemodialysis from 1.19 to 1.38 and 1.43 mmol/l, respectively (mean values) and returned to predialysis values within five and nine hours postdialysis. Serum PTH decreased from 165 ng/l to 55 ng/l (median values) during hemodialysis but two-hour postdialysis the level did not differ significantly from the predialysis level. Serum phosphate decreased from 2.05 mmol/l to 1.11 mmol/l during hemodialysis, and increased slowly towards the predialysis level. The level of pH increased from 7.40 to 7.47 during hemodialysis and reached predialysis level after nine hours. In a multivariate analysis including actual and adjusted ionized calcium, pH, phosphate and PTH, only actual or adjusted ionized calcium was associated with the level of PTH. We conclude that the effect of dialysate calcium on the levels of ionized calcium and PTH is of very short duration postdialysis.
Adult↗
Impaired 1,25-dihydroxyvitamin D production in pregnancy-induced hypertension.
The aim of the study was to evaluate the calcium metabolism in pregnancy-induced hypertension. Fifty-three women with pregnancy-induced hypertension were studied and the control groups comprised 20 women with uncomplicated pregnancies in the third trimester and 51 non-pregnant women, respectively. The mean serum concentrations of 1,25-dihydroxyvitamin D in women with pregnancy-induced hypertension was low (38.6 +/- 21.4 pg/ml) compared to women with uncomplicated pregnancies (91.0 +/- 18.2 pg/ml), but comparable to levels in non-pregnant women (32.2 +/- 11.9 pg/ml). Mean serum levels of PTH and ionized calcium were comparable in women with pregnancy-induced hypertension and women with uncomplicated pregnancies. In conclusion, the calcium metabolism in pregnancy-induced hypertension was changed compared to uncomplicated pregnancies with respect to the serum concentration of 1,25-dihydroxyvitamin D.
Adult↗
Roux-en-Y jejunal bypass abolishes postprandial neuropeptide Y release.
Numerous physiologic aberrations occur after Roux-en-Y bypass procedures. Neuropeptide Y (NPY), a 36 amino acid polypeptide, has been shown to have many effects on gastrointestinal physiology, including alterations in blood flow, motility, and secretion and absorption. Recent work demonstrating a postprandial increase in circulating NPY prompted this investigation into its potential roles after Roux-en-Y bypass. Three groups of rats underwent Roux-en-Y cholangiojejunostomy, jejunojejunostomy, or proximal jejunal transection with reanastomosis. After a 3-month recovery, the animals were tested with both mixed and fat meals. Control animals had rapid increases in circulating NPY after the mixed meal. This response was not seen in either of the Roux-en-Y groups (P less than 0.05). No animals had circulating changes in NPY after the fat meal. Additionally, small intestinal NPY receptor analysis revealed high NPY affinity to the epithelial cells of the proximal small intestine. Our results demonstrate a dependence of postprandial NPY release on proximal small intestinal continuity that is abolished by Roux-en-Y bypass of a jejunal segment. The absence of postprandial elevation in plasma NPY after proximal jejunal bypass and the abundance of NPY receptors in the proximal small intestine merits further investigation into the physiologic roles of NPY in the foregut.
Anastomosis, Roux-en-Y↗
Extrinsic neural contribution to ileal peptide YY (PYY) release.
Peptide YY (PYY) release into the ileal lumen is stimulated by cholecystokinin (CCK) and glucose ingestion. Previous data have implicated vagal activity in the mediation of PYY release into both the systemic circulation and the ileal lumen. The present study was designed to evaluate extrinsic neural involvement in CCK and glucose-stimulated circulating and ileal intraluminal PYY release. Distal ileal Thiry-Vella loops (TVL) of 25 cm were created in seven mongrel dogs. On separate days fasted dogs were given continuous infusions of CCK at 500 ng/kg/hr during the first hour of the study or an oral glucose (1.5 g/kg) tolerance test (OGTT) was performed. Peripheral blood samples and ileal effusates were collected before tests and following either CCK or glucose stimulation for 120 min at 20-min intervals. Ileal PYY recoveries were measured by the instillation and collection of 20 cc of normal saline from the TVL for each 20-min period. The dogs were again tested after surgical denervation of the TVL. OGTT resulted in a significant rise of PYY recovery from the TVL (P less than 0.05), while not affecting circulating PYY. Intravenous CCK resulted in significant increases in both plasma and ileal PYY concentrations (P less than 0.05). Denervation of the TVL decreased PYY recovery from the TVL after both CCK and OGTT, whereas this procedure did not affect circulating PYY levels or basal luminal levels. These data demonstrate the inhibition of CCK- and glucose-stimulated ileal PYY recovery from denervated ileal loops. The extrinsic neural pathways are involved in the mediation of glucose- and CCK-stimulated mechanisms for ileal PYY release.
Animals↗
Increasing parathyroid hormone concentrations in untreated primary hyperparathyroidism.
Twenty-four patients with mild to moderate primary hyperparathyroidism were followed for an average of 2.45 years with serial determinations of serum ionized calcium and intact parathyroid hormone (PTH). For the entire group serum ionized calcium remained stable, whereas serum PTH increased significantly. Eleven patients (group 1) demonstrated a significant increase in PTH with time. The remaining 13 patients formed group 2. Comparison of the changes (%) in each subgroup showed a small but significant increase in serum ionized calcium of 2.6% with time in group 1, while serum PTH increased by 78%. In group 2 serum ionized calcium remained stable whereas PTH increased modestly by 22%. Serum concentrations of creatinine were stable throughout the follow-up period in both groups. Despite the greater precision of serum ionized calcium, measurements of intact PTH are evidently more sensitive than measurements of serum ionized calcium for the detection of progression in primary hyperparathyroidism.
Adult↗
Increased activity of ionised calcium in gall bladder bile in gall stone disease.
The actual activity of ionised calcium (Ca2+) in gall bladder bile determined with an ion-selective electrode was significantly higher in patients with gall stone disease (n = 15) than in patients without gall stones (n = 10) (0.43 mmol/kg v 0.31 mmol/kg; p < 0.05). No change in the Ca2+ activity in any of the gall bladder bile samples was observed during equilibration with CO2. During titration with HCl/NaOH, however, the Ca2+ activity fell with increasing pH in a biphasic manner, with the breaking point occurring at a significantly lower median pH in patients with gall stones than in patients without (pH 7.1 v 8.2; p < 0.0001). The combination of a higher activity of calcium in bile and precipitation of bile salts taking place at a lower pH in patients with gall stone disease than in patients without gall stones suggests a major role for calcium and pH in the pathogenesis of gall stones. Strict anaerobic sampling is not necessary for the measurements of Ca2+ in gall bladder bile, because the Ca2+ was not significantly affected by the changes in pCO2. The metabolic studies suggest, however, that simultaneous measurements of the activity of Ca2+ and pH is important in order to interpret data for the calcium activity in gall bladder bile.
Adult↗
Inappropriate hypercalcitriolemia in ileum-resected patients with Crohn's disease.
Twelve patients who had undergone ileal resection because of Crohn's disease were studied for measurements of serum 25-hydroxyvitamin D3 (25-OHD3), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], intact parathyroid hormone (PTH), ionized calcium and phosphate in median 6 years after the intestinal resection. 24 normal subjects matched for age, sex and season served as controls. Despite a reduced level of 25-OHD3 (p less than 0.05) and normal levels of ionized calcium, PTH, phosphate and renal function the median level of 1,25(OH)2D3 was significantly raised (p less than 0.001). Further analysis showed that the inappropriately increased level of 1,25(OH)2D3 was significantly positive related to the concentrations of its substrate (25-OHD3) and PTH. The cause for inappropriate hypercalcitriolemia is uncertain. Contribution from extrarenal 1-hydroxylation of 25-OHD3 as in sarcoidosis is suggested.
Adult↗