Assessment of bone mineral density and risk factors in children completing treatment for acute lymphoblastic leukemia.

BACKGROUND: Reduced bone mineral density and increased fracture risk have been reported in children with cancer. In this study, we aimed to determine the growth and bone mineral density (BMD) of the children off chemotherapy for acute lymphoblastic leukemia, and the probable risk factors. PROCEDURE: The age, anthropometric measurements, lumbar spine BMDs were recorded in 70 children. The risk factors on BMD; daily calcium intake, the time interval from the completion of the chemotherapy, cranial radiotherapy, cumulative steroid dose, decrease in physical activity were investigated. Serum calcium, phosphate, alkaline phosphates, magnesium, insulin-like growth factor-1 (IGF-1) and 25 (OH) vitamin D levels were determined. RESULTS: The mean height percentile at the time of diagnosis was decreased from the value of 53 to a value of 47 at the beginning of the study (P=0.071). Of them; 44% had osteoporosis, 41% had osteopenia, and the rest had normal BMD. BMD z-scores were decreased during the first 2 years from the completion of the treatment. There was a positive correlation between BMD z-scores and daily calcium intake (CC=0.366, P=0.0015). A negative correlation was determined between the time spent on TV and computers and BMD z-scores (CC=-0.464, P=0.0019). Serum IGF-1 and 25 (OH) vitamin D levels of patients were significantly lower than controls (P=0.033). CONCLUSIONS: Our data revealed that 85% of the survivors had bone mineralization defect. BMDs and z scores were decreased during the first 2 years from the completion of the treatment and then gradually began to increase. The most important risk factor for decreased BMD was low daily calcium intake. Therefore, patients and their families should be encouraged to take sufficient amount of calcium. Prophylactic vitamin D may also be supplemented.

Endotoxin increases plasma leptin and ghrelin levels in dogs.

OBJECTIVE: Evaluations of plasma leptin and ghrelin levels and their relations with circulating levels of proinflammatory mediators, stress hormones, and biochemical markers of hepatorenal injury during experimental endotoxemia in dogs. SETTING: Uludag University. DESIGN: Placebo-controlled animal study. ANIMALS: Adult mongrel dogs (n = 16). INTERVENTIONS: Intravenous injection of endotoxin (1 mg/kg) and blood sample withdrawal before and at 0.5-48 hrs posttreatment. MEASUREMENTS AND MAIN RESULTS: Mean baseline plasma leptin and ghrelin levels were 2.4 +/- 0.1 ng/mL and 867 +/- 58 pg/mL, respectively. Plasma leptin and ghrelin increased significantly by 16% (p < .05) and 72% (p < .001) at 0.5 hr, and they remained elevated by 33-41% (p < .001) and 59-74% (p < .001) at 48 hrs after administration of endotoxin, respectively. There was positive correlation (r = .844; p < .001) between plasma leptin and ghrelin levels in endotoxin-treated dogs. Endotoxemia was associated with several-fold elevations in circulating levels of stress hormones, proinflammatory mediators, and hepatorenal injury markers. Plasma leptin and ghrelin levels in endotoxin-treated dogs were correlated with serum nitric oxide (r = .955 and r = .890; p < .001), procalcitonin (r = .825 and r = .716; p < .001), cortisol (r = .823 and r = .786; p < .001), and hepatorenal injury markers (r = .580 to .745 and r = .393 to .574; p < .05 to .01). CONCLUSIONS: Circulating leptin and ghrelin levels increase during endotoxemia, and these increases are associated with elevated levels of proinflammatory mediators, stress hormones, and serum biochemical markers for hepatorenal dysfunction.

Choline, CDP-choline or phosphocholine increases plasma glucagon in rats: involvement of the peripheral autonomic nervous system.

The present study was designed to test the effects of choline, cytidine-5'-diphosphocholine (CDP-choline) and phosphocholine on plasma glucagon concentrations in rats. Intraperitoneal (i.p.) injection of 200-600 micromol/kg of choline, CDP-choline or phosphocholine produced a dose-dependent increase in plasma glucagon and choline concentrations. Pretreatment with hexamethonium (15 mg/kg; i.p.), a peripherally-acting ganglionic nicotinic acetylcholine receptor antagonist, entirely blocked the increases in plasma glucagon by 600 micromol/kg of choline, CDP-choline or phosphocholine. The increases in plasma glucagon by these choline compounds was reduced significantly (P<0.01) by about 25% by pretreatment with atropine methylnitrate (2 mg/kg), a peripherally-acting muscarinic acetylcholine receptor antagonist. Blockade of central acetylcholine receptors did not alter the increase in plasma glucagon induced by i.p. choline (600 micromol/kg). While alpha(2)-adrenoceptor blockade or bilateral adrenalectomy attenuated the increase in plasma glucagon evoked by choline compounds, blockade of alpha(1)- or beta-adrenoceptors or chemical sympathectomy failed to alter this increase. Intracerebroventricular (i.c.v.) choline (1.5 micromol) administration also increased plasma glucagon; the effect was blocked by central pretreatment with a neuronal type nicotinic acetylcholine receptor antagonist, mecamylamine (50 microg; i.c.v.) or the neuronal choline uptake inhibitor, hemicholinium-3 (20 microg; i.c.v.). These data show that choline, CDP-choline or phosphocholine increases plasma glucagon concentrations by increasing peripheral nicotinic and muscarinic cholinergic neurotransmissions. Central choline also increases plasma glucagon by augmenting central nicotinic cholinergic neurotransmission by acting presynaptically. Stimulation of adrenal medullary catecholamine release and subsequent activation of alpha(2)-adrenoceptors are mainly involved in the increase in plasma glucagon induced by choline, CDP-choline or phosphocholine.

Peripheral administration of CDP-choline and its cholinergic metabolites increases serum insulin: muscarinic and nicotinic acetylcholine receptors are both involved in their actions.

The present study was designed to test the effects of CDP-choline and its metabolites on serum insulin concentrations in rats and to investigate the involvements of cholinergic and adrenergic receptors in the effect. Intraperitoneal (i.p.) administration of CDP-choline (200-600 micromol/kg) increased serum insulin in a dose- and time-related manner. Equivalent doses (200-600 micromol/kg; i.p.) of phosphocholine or choline also increased serum insulin dose-dependently. Serum-free choline concentrations increased several-fold following i.p. administration of CDP-choline, phosphocholine or choline itself. In contrast, equivalent doses of cytidine monophosphate and cytidine failed to alter serum insulin concentrations. The increases in serum insulin induced by i.p. 600 micromol/kg of CDP-choline, phosphocholine or choline were abolished by pretreatment with the ganglionic nicotinic acetylcholine receptor antagonist hexamethonium (15 mg/kg; i.p.), or by the muscarinic receptor antagonist atropine methylnitrate (2 mg/kg; i.p.). Pretreatment with prazosin (0.5 mg/kg; i.p.), an alpha(1)-adrenoceptor antagonist, or yohimbine (5 mg/kg, i.p.), an alpha(2)-adrenoceptor antagonist, enhanced slightly the increases in serum insulin in response to 600 micromol/kg of CDP-choline, phosphocholine and choline. Serum insulin also increased following central administration of choline; the effect was blocked by intracerebroventricularly injected atropine, mecamylamine or hemicholinium-3 (HC-3). It is concluded that CDP-choline or its cholinergic metabolites phosphocholine and choline increases circulating insulin concentrations by increasing muscarinic and nicotinic cholinergic neurotransmission in the insulin secreting beta-cells.

Central choline suppresses plasma renin response to graded haemorrhage in rats.

Central administration of choline increases blood pressure in normotensive and hypotensive states by increasing plasma concentrations of vasopressin and catecholamines. We hypothesized that choline could also modulate the renin-angiotensin pathway, the third main pressor system in the body. Plasma renin activity (PRA), which serves as an index of the function of the peripheral renin-angiotensin system, was determined in rats subjected to graded haemorrhage following central choline administration. Intracerebroventricular (i.c.v.) injection of choline (12.5-150 microg), a precursor of the neurotransmitter acetylcholine (ACh), inhibited the increase in PRA in rats subjected to graded haemorrhage by sequential removal of 0.55 mL blood/100 g bodyweight. Choline, in the range 50-150 microg, increased blood pressure. Intraperitoneal (i.p.) administration of 150 microg choline failed to alter blood pressure and plasma renin responses to graded haemorrhage. Administration of a higher dose (90 mg/kg, i.p.) of choline decreased blood pressure and enhanced PRA in the first two blood samples obtained during the graded haemorrhage. Physostigmine (10 microg, i.c.v.), ACh (10 microg, i.c.v.), carbamylcholine (10 microg, i.c.v.) and cytidine 5'-diphosphocholine (CDP-choline; 250 microg, i.c.v.) increased blood pressure and attenuated plasma renin responses to graded haemorrhage. Inhibition of PRA by i.c.v. choline was abolished by i.c.v. pretreatment with mecamylamine (50 microg), but not atropine (10 microg). Blood pressure responses to choline (150 microg) were attenuated by pretreatment with both mecamylamine and atropine. Inhibition of PRA in response to central choline administration was associated with enhanced plasma vasopressin and catecholamine responses to graded haemorrhage. Pretreatment of rats with a vasopressin antagonist reversed central choline-induced inhibition of plasma renin responses to graded haemorrhage without altering the blood pressure response. In conclusion, central administration of choline inhibits the plasma renin response to graded haemorrhage. Nicotinic receptor activation and an increase in plasma vasopressin appear to be involved in this effect.

Evaluation of platelet count and its association with plateletcrit, mean platelet volume, and platelet size distribution width in a canine model of endotoxemia.

BACKGROUND: Platelets are of great importance in the pathogenesis of endotoxemia. Although thrombocytopenia is used as a diagnostic sign of endotoxemia, changes in values for platelet indices (plateletcrit [PCT], mean platelet volume [MPV], and platelet size distribution width [PDW]) in response to endotoxin are still unknown. OBJECTIVE: The aim of this study was to evaluate platelet count and its relations with platelet indices in a canine model of endotoxemia. METHODS: Twenty dogs were divided into 2 groups of 10 each, and treated intravenously with Escherichia coli endotoxin (1 mg/kg) or vehicle. Venous blood samples were collected before treatment (0 hour) and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after treatment. Platelet counts and indices were determined on a CELL-DYN hematology analyzer. RESULTS: The platelet count and PCT decreased by a mean of 73% and 93%, respectively (P<.001), at 0.5 hour, and remained 70% and 85% lower than baseline values (P<.001) for 24 hours after endotoxin injection. MPV and PDW increased by a mean of 28% and 45%, respectively (P<.01), at 0.5 hour, and remained increased by 7% and 16% over baseline values for 24 hours (P<.01-.001). Platelet count correlated positively with PCT (P<.001), but correlated negatively with MPV (P<.001) and PDW (P<.01). CONCLUSIONS: Changes in platelet count and its association with platelet indices may reflect changes in platelet production and reactivity. Platelet indices have potential value in the diagnosis and monitoring of dogs and humans with endotoxemia.

[Homocysteine levels in patients with obstructive sleep apnea syndrome]. / Obstrüktif uyku apne sendromlu hastalarda homosistein düzeyleri.

The exact mechanism of development of cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS) remains to be unknown. The role of homocysteine in atherosclerotic disease process has become well established over the past ten years. Our aim was to study to compare homoscysteine levels between OSAS and control levels. Sixty-two subjects with OSAS and twelve similar controls in age, gender, body mass index, smoking and coronary heart disease were included in this prospective study. Serum levels of homocysteine (13.5 +/- 6.0 micromol/L vs. 10.2 +/- 2.9 micromol/L, p= 0.03) in the OSAS group were significantly greater than those in the control group. Logistic regression analyses showed that OSAS (Odds ratio: 9.08 95% CI 2.347-35.120; p= 0.001) was independent risk factors for high levels of serum homocysteine in age, smoking status, diabetes mellitus and coronary heart disease. We conclude that homocysteine may be an important factor for development of cardiovascular disease in patients with OSAS.

Relationship between serum substance P levels and daytime sleepiness in obstructive sleep apnea syndrome.

OBJECTIVE: We hypothesized that intermittent hypoxia might influence serum substance P levels, and that this effect might in turn contribute in excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: Fifty-five patients with newly diagnosed OSAS and 15 age-matched nonapneic control subjects were enrolled in this study. Full polysomnography was performed in all patients. Single blood samples were drawn between 8:00 am and 9:00 am after the sleep study. Substance P levels were analyzed with a competitive enzyme immunoassay (substance P EIA kit; Cayman Chemical; Ann Arbor, MI). RESULTS: There were no significant differences in age, gender, body mass index, smoking habit, and snoring between the two groups. Serum substance P levels in the OSAS group were significantly lower than that in the control group (p < 0.0001). Serum substance P levels were positively correlated with rapid eye movement sleep (r = 0.330, p = 0.049) and slow-wave sleep (r = 0.324, p = 0.049) phases. Serum substance P levels were negatively correlated with Epworth sleepiness scale score (r = - 0.253, p = 0.048), number of total apneas during the night (r = - 0.247, p = 0.036), number of respiratory events during the night (r = - 0.266, p = 0.024), apnea-hypopnea index (r = - 0.287, p = 0.015), respiratory arousal index (r = - 0.267, p = 0.026), time spent in apnea and hypopnea (r = - 0.307, p = 0.01), average oxygen desaturation (r = - 0.265, p = 0.026), and oxygen desaturation index (r = - 0.254, p = 0.031). CONCLUSION: We concluded that EDS seen in some of the OSAS patients might be associated with various pathophysiologic mechanisms including substance P levels.

Cardiovascular effects of CDP-choline and its metabolites: involvement of peripheral autonomic nervous system.

Intraperitoneal administration of CDP-choline (200-900 micromol/kg) increased blood pressure and decreased heart rate of rats in a dose- and time-dependent manner. These responses were accompanied by elevated serum concentrations of CDP-choline and its metabolites phosphocholine, choline, cytidine monophosphate and cytidine. Blood pressure increased by intraperitoneal phosphocholine (200-900 micromol/kg), while it decreased by choline (200-600 micromol/kg) administration; phosphocholine or choline administration (up to 600 micromol/kg) decreased heart rate. Intraperitoneal cytidine monophosphate (200-600 micromol/kg) or cytidine (200-600 micromol/kg) increased blood pressure without affecting heart rate. Pressor responses to CDP-choline, phosphocholine, cytidine monophosphate or cytidine were not altered by pretreatment with atropine methyl nitrate or hexamethonium while hypotensive effect of choline was reversed to pressor effect by these pretreatments. Pretreatment with atropine plus hexamethonium attenuated or blocked pressor response to CDP-choline or phosphocholine, respectively. Heart rate responses to CDP-choline, phosphocholine and choline were blocked by atropine and reversed by hexamethonium. Cardiovascular responses to CDP-choline, phosphocholine and choline, but not cytidine monophosphate or cytidine, were associated with elevated plasma catecholamines concentrations. Blockade of alpha-adrenoceptors by prazosin or yohimbine attenuated pressor response to CDP-choline while these antagonists blocked pressor responses to phosphocholine or choline. Neither bilateral adrenalectomy nor chemical sympathectomy altered cardiovascular responses to CDP-choline, choline, cytidine monophosphate or cytidine. Sympathectomy attenuated pressor response to phosphocholine. Results show that intraperitoneal administration of CDP-choline and its metabolites alter cardiovascular parameters and suggest that peripheral cholinergic and adrenergic receptors are involved in these responses.

Serum leptin and ghrelin levels in response to methylprednisolone injection in healthy dogs.

The aim of this study was to investigate the effects of methylprednisolone treatment on serum leptin and ghrelin levels in healthy dogs (n=40). After 14 h of fasting, the dogs were injected intramuscularly with saline (control group) or methylprednisolone (1, 5 or 10mg/kg). Blood samples were collected prior to (baseline) and 2, 3, 4, 8, 12 and 24h subsequent to the treatments. Serum leptin and ghrelin were measured by radioimmunoassay. The mean baseline serum leptin and ghrelin were 2.5+/-0.1 ng/mL (n=40) and 35.0+/-2.1 pg/mL (n=40), respectively. In the control dogs, serum leptin, but not ghrelin levels showed a significant fluctuation during the 24h observation period. Serum leptin increased significantly (p<0.05-0.01) between 2 and 12h after 1mg/kg of methylprednisolone. Serum leptin levels showed biphasic response to 5mg/kg of methylprednisolone: its level decreased to 1.9+/-0.1 ng/mL (p<0.01) at 2h and increased at 12h (2.6+/-0.1 ng/mL) (p<0.01). In response to 10mg/kg of methylprednisolone, serum leptin levels decreased significantly (p<0.01) for 24h. Serum ghrelin levels decreased to 19+/-5 pg/mL at 2-3h (p<0.01) or increased to 87+/-18 pg/mL at 3-8h (p<0.05-0.01) after 1mg/kg of methylprednisolone or 10mg/kg of methylprednisolone, respectively. Serum ghrelin levels did not change at any time point during 24h observation period after 5mg/kg of methylprednisolone. There was a significant (p<0.001) inverse correlation (r=-0.635) between serum leptin and ghrelin levels. In conclusion, we found that methylprednisolone increases or decreases serum leptin and ghrelin levels depending upon its dose and there is a negative correlation between serum leptin and ghrelin levels after methylprednisolone administration.

Intravenous administration of choline or cdp-choline improves platelet count and platelet closure times in endotoxin-treated dogs.

This study was performed to assess the effects of intravenous choline chloride and cytidine-5'-diphosphate choline (CDP-choline) treatments on circulating platelet, white blood cell, and red blood cell counts and platelet functions in response to endotoxin. Saline (0.2 mL/kg), choline chloride (20 mg/kg), or CDP-choline (70 mg/kg) were given intravenously three times at 4-h intervals, and endotoxemia was induced by endotoxin (E. coli 055:B5, 20 microg/kg) infusion, 5 min after the first treatment. Blood samples were collected before and at multiple time points after the challenge, for a panel of hematologic parameters and platelet closure times measured by PFA-100. In saline-treated dogs, circulating platelet counts decreased by 85% (P < 0.001) at 0.5 h and remained low by 36%-80% (P < 0.5-0.001) 1-12 h after endotoxin. Circulating WBC counts decreased by 80%-90% (P < 0.001) at 0.5-2 h, and increased (P < 0.001) by 190% 12 h after the endotoxin. In response to endotoxin, RBCs increased by 10%-13% (P < 0.05) at 1-12 h. Endotoxin-induced decline in circulating platelets was attenuated at 0.5 h (P < 0.05-0.01) and reversed at 1-12 h (P < 0.05-0.001) by choline. Platelet closure times were shortened from 81 +/- 10 s and 135 +/- 10 s to 29 +/- 5 s (P < 0.001) and 60 +/- 3 s (P < 0.001) at 0.5 h, and prolonged (P < 0.001) at 1-8 h after endotoxin induction. Endotoxin-induced shortening in platelet closure times was attenuated (P < 0.05) and blocked (P < 0.01) by choline and CDP-choline, respectively. These results showed that choline and CDP-choline treatments improved circulating platelet counts and platelet function during endotoxemia in dogs.

Endotoxin alters serum-free choline and phospholipid-bound choline concentrations, and choline administration attenuates endotoxin-induced organ injury in dogs.

This study in dogs was performed to assess circulating choline status during endotoxemia and to determine whether choline administration can protect dogs from endotoxin-induced tissue injuries. Baseline serum-free and phospholipid-bound choline concentrations were 19.2 +/- 0.6 micromol/L and 3700 +/- 70 micromol/L, respectively. After intravenous endotoxin infusion, serum-free choline concentrations decreased by 14% to 49% (P < 0.05-0.001) at 2 to 6 h after 0.02 mg/kg endotoxin, and increased by 23% to 98% (P < 0.05-0.001) at 1 to 48 h after 1 mg/kg endotoxin. Serum phospholipid-bound choline concentrations increased by 19% to 27% (P < 0.05) at 12 to 24 h or by 18% to 53% (P < 0.05-0.001) at 1 to 48 h after 0.02 or 1 mg/kg endotoxin, respectively. The changes in serum-free and -bound choline levels in response to endotoxin were accompanied by dose- and time-related elevations in serum cortisol and biochemical markers for tissue injury and/or organ dysfunction. Intravenous administration of choline (20 mg/kg) 5 min before, and 4 and 8 h after endotoxin (1 mg/kg) attenuated endotoxin-induced elevations in serum alanine aminotransferase (P < 0.05-0.001), aspartate aminotransferase (P < 0.05-0.001), gamma-glutamyl transferase (P < 0.05-0.001), alkaline phosphatase (P < 0.05-0.001), lactate dehydrogenase (P < 0.05-0.001), myocardial creatine kinase (P < 0.001), urea (P < 0.05-0.01), creatinine (P < 0.05), uric acid (P < 0.01-0.001), and tissue necrosis factor-alpha (P < 0.001). Choline also attenuated alanine aminotransferase (P < 0.05-0.01), alkaline phosphatase (P < 0.05-0.01), lactate dehydrogenase (P < 0.05-0.01), creatine kinase (P < 0.05-0.001), myocardial creatine kinase (P < 0.05-0.001), and uric acid (P < 0.05-0.01), but failed to alter the serum urea, creatinine, aspartate aminotransferase, and gamma-glutamyl transferase responses to 0.02 mg/kg endotoxin. These data show that choline status is altered during endotoxemia and that choline administration diminishes endotoxin-induced tissue injury.

Choline status in newborns, infants, children, breast-feeding women, breast-fed infants and human breast milk.

This study assessed the choline status in newborns, infants, children, breast-feeding women, breast milk, infant formula, breast-fed and formula-fed infants. The serum free choline level was 35.1+/-1.1 micromol/L at birth and decreased to 24.2+/-1.6, 18.1+/-0.8, 16.3+/-0.9, 14.3+/-0.8, 12.9+/-0.6 or 10.9+/-0.6 micromol/L at 22-28, 151-180, 331-365, 571-730, 731-1095 or 4016-4380 days after birth, respectively. The serum phospholipid-bound choline level was 1997+/-75 micromol/L at birth and increased gradually to 2315+/-190 or 2572 +/-100 micromol/L at 571-730 or 4016-4380 days after birth, respectively. In breast-feeding women, serum free and phospholipid-bound choline levels were doubled at 12-28 days after birth, they decreased toward the control values with time. Free choline, phosphocholine and glycerophosphocholine were major choline compounds in breast milk. Their concentrations in mature milk were much greater than in colostrum and serum. Choline contents of breast milk varied greatly between mothers, and milk free choline levels were correlated with serum free choline (r=.541; P<.001), phospholipid-bound choline (r=.527; P<.001) and glycerophosphocholine (r=.299; P<.01) concentrations and lactating days (r=.520; P<.001). In breast-fed infants, serum free choline concentrations were correlated with free choline (r=.47; P<.001), phosphocholine (r=.345; P<.002), glycerophosphocholine (r=.311; P<.01) and total choline (r=.306; P<.01) contents of breast milk. Serum free choline concentration in formula-fed infants was lower than breast-fed infants. These data show that (a) circulating choline status is elevated during infancy and lactation, (b) choline contents of breast milk vary between mothers and milk free choline contents are influenced by maternal circulating choline status, and (c) the choline contents of breast milk can influence infants' circulating choline status.

Hyperglycemia induced by intracerebroventricular choline: involvement of the sympatho-adrenal system.

Intracerebroventricular (i.c.v.) injection of choline (75-300 microg) produced a dose-dependent increase in blood glucose levels. Pre-treatment with the nicotinic acetylcholine receptor antagonist, mecamylamine (50 microg, i.c.v.) blocked the hyperglycemia induced by choline (150 microg, i.c.v.), but the response was not affected by pre-treatment with the muscarinic acetylcholine receptor antagonist, atropine (10 microg, i.c.v.). Pre-treatment with the neuronal choline uptake inhibitor, hemicholinium-3 (20 microg, i.c.v.), attenuated the hyperglycemia induced by choline. The hyperglycemic response to choline was associated increased plasma levels of adrenaline and noradrenaline. The hyperglycemia elicited by choline was greatly attenuated by bilateral adrenalectomy, and entirely blocked by either surgical transection of the splanchnic nerves or by pre-treatment with the alpha-adrenoceptor antagonist, phentolamine. These data show that choline, a precursor of acetylcholine, increases blood glucose and this effect is mediated by central nicotinic acetylcholine receptor activation. An increase in sympatho-adrenal activity appears to be involved in the hyperglycemic effect of choline.

Changes of plasma free choline and choline-containing compounds' concentrations and choline loss during hemodialysis in ESRD patients.

OBJECTIVES: This study was undertaken to determine the changes in plasma free choline and choline-containing compounds in end stage renal disease (ESRD) and to determine if they were lost into the dialysate during hemodialysis. DESIGN AND METHODS: Plasma and dialysate free choline, phosphocholine and phospholipid-, phosphatidylcholine-, sphingomyelin-bound choline were measured before, during and after hemodialysis. RESULTS: Plasma free and bound choline concentrations (mean +/- standard error of the mean) were 12.9 +/- 0.6 and 2697 +/- 57 microM or 37.3 +/- 0.9 and 2792 +/- 98 microM in controls or in ESRD patients, respectively. Free choline concentrations were correlated (r = 0.598; p < 0.001) with the time the patients were subjected to hemodialysis. Plasma free choline and phosphocholine concentrations are decreased by a total of -8.1 +/- 0.6 micromol/L and -88 +/- 8 micromol/L, respectively; phospholipid-, phosphatidylcholine- and sphingomyelin-bound choline are increased, during hemodialysis. Patients lost about 350 micromoles of choline into the dialysate during hemodialysis. CONCLUSION: Plasma free choline concentrations are elevated in ESRD, and a considerable amount of choline is lost into the hemodialysate.

Free choline and phospholipid-bound choline concentrations in serum and dialysate during peritoneal dialysis in children and adults.

OBJECTIVES: This study tested whether continuous ambulatory peritoneal dialysis (CAPD) changes free or phospholipid-bound choline concentrations in serum or peritoneal dialysis fluid of patients with end stage renal disease (ESRD). DESIGN AND METHODS: Serum and dialysate choline and phospholipid-bound choline were measured before, during and after 6 h CAPD. RESULTS: Serum choline concentrations were higher in patients with ESRD compared with age-matched controls. CAPD lowered serum choline concentrations significantly although it did not influence phospholipid-bound choline. Choline accumulated in the dialysate, reaching 28.4 +/- 2.7 microM in children and 18.2 +/- 1.4 microM in adults, during six hours CAPD; phospholipid-bound choline increased to 22.9 +/- 2.5 microM and 10.8 +/- 1.4 microM in children and adults, respectively. The total daily loss of choline into the dialysate was 181 +/- 20 micromoles in children and 260 +/- 18 micromoles in adults. CONCLUSION: CAPD causes a substantial loss of choline into peritoneal dialysates and reduces serum choline concentrations significantly.

Serum free and phospholipid-bound choline decrease after surgery and methylprednisolone administration in dogs.

We designed this study to determine whether serum free and phospholipid-bound choline concentrations change after surgery or methylprednisolone treatment in dogs and rats. In dogs, serum free and phospholipid-bound choline concentrations were decreased by 29% and 17% immediately after abdominal-pelvic surgery under xylasine+ketamine anesthesia, respectively, and both remained low for 24 h. Serum cortisol was elevated after surgery. The elevation in serum cortisol was inversely correlated with the decreases in free (r=-0.737; P<0.001) and phospholipid-bound (r=-0.771; P<0.001) choline concentrations. After methyprednisolone administration (5-20 mg/kg) free and phospholipid-bound choline concentrations decreased in a dose- and time-dependent manner. In rats, either surgery or methylprednisolone failed to alter serum free choline concentrations while phospholipid-bound choline decreased after surgery. These data show that the decrease in serum choline after surgery results from the increase in circulating glucocorticoids.

The decline in serum choline concentration in humans during and after surgery is associated with the elevation of cortisol, adrenocorticotropic hormone, prolactin and beta-endorphin concentrations.

Serum choline concentrations decrease during and after surgery. We undertook this study to determine whether the decrease of choline is associated with an increase in stress hormones. In 16 patients undergoing abdominal surgery with general anesthesia, circulating choline cortisol, prolactin, adrenocorticotropic hormone (ACTH) and -endorphin levels were measured before, during and after surgery. Choline levels decreased by 41% (P<0.01) during surgery, remained 15-38% decreased for 48 h, and returned to preoperative values 72 h after surgery. The decrease in serum choline was associated and inversely correlated with the increase in serum cortisol (P<0.001; r = -0.642), prolactin (P<0.001; r = -0.756), -endorphin (P<0.001; r = -0.726) and ACTH (P<0.01; r = -0.458). In conclusion, we found that abdominal surgery induces a decline in serum choline associated with an increase in circulating cortisol, prolactin, ACTH and -endorphin.

Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role of obesity.

AIM: The aim of this study was to investigate the relationship among plasma leptin, ghrelin, adiponectin, resistin levels, and obstructive sleep apnea syndrome (OSAS). METHODS: Fifty-five consecutive newly diagnosed OSAS patients and 15 age-matched nonapneic controls were enrolled in this study. After sleep study between 8:00 AM and 9:00 AM on the morning, venous blood was obtained in the fasting state to measure ghrelin and adipokines. RESULTS: Serum ghrelin levels of OSAS group were significantly (P < 0.05) higher than those of the control group. No significant difference was noted in the levels of leptin, adiponectin, and resistin in OSAS group when compared to controls. There was a significant positive correlation between ghrelin and apnea-hypopnea index (AHI) (r = 0.237, P < 0.05) or the Epworth sleepiness scale (ESS) (r = 0.28, P < 0.05). There was also a significant positive correlation between leptin and body mass index (r = 0.592, P < 0.0001). No significant correlation was observed between leptin, adiponectin, resistin, and any polysomnographic parameters. CONCLUSION: Our findings demonstrated that serum ghrelin levels were higher in OSAS patients than those of control group and correlated with AHI and ESS. Further studies are needed to clarify the complex relation among OSAS, obesity, adipokines, and ghrelin.