24-hour urine metanephrine excretion in patients diagnosed with adrenal incidentaloma: impact of commonly used drugs on a clinical decision.

INTRODUCTION: Incidentaloma is an adrenal tumor detected during diagnostic imaging performed for extra­adrenal causes. Evaluation of metanephrine concentrations in a 24­hour urine collection can be a significant challenge in patients with multiple medications and comorbidities. OBJECTIVES: The aim of this study was to evaluate the effect of commonly used groups of drugs on metanephrine levels in the 24­hour urine collection. PATIENTS AND METHODS: A total of 1051 patients with adrenal mass below 10 Hounsfield units on unenhanced computed tomography were included in the study. Patients diagnosed with Cushing or Conn syndrome, adrenal carcinoma, pheochromocytoma, active extra­adrenal malignant neoplasms, and exacerbation of severe illnesses were excluded. Metanephrine, normetanephrine, and 3­methoxytyramine in the 24­hour urine collection were measured by high­performance liquid chromatography with electrochemical detection. Information on concomitant medication (ß­blockers, calcium channel blockers [CCBs], loop diuretics, thiazide diuretics, potassium­sparing diuretics, α­blockers, angiotensin­converting enzyme inhibitors / angiotensin II receptor blockers, metformin, nonmetformin antidiabetic drugs [NMADs], lipid­lowering drugs, proton pump inhibitors, levothyroxine, thyreostatics, antidepressants, neuroleptics, benzodiazepines, glucocorticosteroids, inhaled B­receptor agonists, and ipratropium) was collected from each patient. RESULTS: The urinary excretion of normetanephrine was significantly higher in the patients on ß­blockers, CCBs, loop diuretics, α­blockers, NMADs, and neuroleptics. α­Blockers increased urine metanephrine concentration, and NMADs, antidepressants, and glucocorticosteroids lowered it. There was no association between the analyzed drugs and urinary 3­methoxytyramine level. CONCLUSIONS: Many drug groups interfere with the measurement of urinary fractionated metanephrines. These interactions should be taken into account during interpretation of a hormonal evaluation, as they can be crucial for further management, especially for making a decision on surgical treatment.

Amino acid profile in overweight and obese prepubertal children - can simple biochemical tests help in the early prevention of associated comorbidities?

Background: It is accepted that plasma branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are closely related to metabolic risk. Arterial hypertension, metabolic syndrome, endothelial dysfunction, inflammation, and metabolic dysfunction-associated fatty liver disease (MAFLD) are frequently seen in obese patients. Many attempts have been made to find biochemical indicators for the early detection of metabolic complications in children. It is not known if different amino acid profiles and BCAA and AA concentrations in overweight and obese children correlate with chemerin, proinflammatory, and simple biochemical markers. Thus, the study aimed to find out the early markers of cardiovascular disease and MAFLD in overweight and obese children. Materials and methods: The study included 20 overweight and obese children (M/F 12/8; mean age 7.7 ± 2.3 years; BMI 26.8 ± 5.0 kg/m2) and 12 non-obese children (control group) (M/F 4/8; mean age 6.5 ± 2.2 years; BMI 14.8 ± 1.5 kg/m2). The following plasma amino acids were measured: aspartic acid, glutamic acid, serine, asparagine, glycine, glutamine, taurine, histidine, citrulline, threonine, alanine, arginine, proline, tyrosine, methionine, valine, isoleucine, leucine, phenylalanine, tryptophan, ornithine, and lysine. Chemerin, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and basic biochemistry parameters were measured. Results: The mean plasma levels of leucine, isoleucine, valine, phenylalanine, tyrosine, glutamic acid, and alanine were significantly higher in overweight and obese children than in the control group (p<0.03-p<0.0004). Conversely, the mean values of serine, asparagine, glutamine, and citrulline were significantly lower in overweight and obese children than in the control group (p<0.03-p<0.0007). Isoleucine, leucine, valine (BCAAs) tyrosine, and phenylalanine (AAAs) levels showed a positive correlation with uric acid, ALT, hs-CRP, and chemerin (r=0.80-0.36; p<0.05-p<0.00001), but not with IL-6. The mean values of glucose, IL-6, hs-CRP, chemerin, uric acid, and ALT were significantly higher in overweight and obese children than in the control group (p<0.03-p<0.00002). In contrast, the lipid profile did not differ between groups. Conclusion: An abnormal amino acid profile in overweight and obese pre-pubertal children, accompanied by elevated ALT and UA observed in the studied cohort, may suggest early metabolic disturbances that can potentially lead to metabolic syndrome, or MAFLD, and increased cardiovascular risk.

Biliary Amino Acids and Telocytes in Gallstone Disease.

The role of amino acids in cholesterol gallstone formation is not known. Therefore, the aim of the study was to determine the amino acid profile in the bile of patients with and without cholecystolithiasis in relation to bile lithogenicity and telocyte numbers within the gallbladder wall. The study included 23 patients with cholecystolithiasis and 12 gallstone-free controls. The levels of free amino acids in the bile were measured, and telocytes were identified and quantified in the gallbladder muscle wall. The mean values of valine, isoleucine, threonine, methionine, phenylalanine, tyrosine, glutamic acid, serine alanine, proline and cystine were significantly higher in the study group than in the controls (p from 0.0456 to 0.000005), and the mean value of cystine was significantly lower in patients with gallstone disease than in the controls (p = 0.0033). The relationship between some of the amino acids, namely alanine, glutamic acid, proline, cholesterol saturation index (CSI) and the number of telocytes was significant (r = 0.5374, p = 0.0051; r = 0.5519, p = 0.0036; and r = 0.5231, p = 0.0071, respectively). The present study indicates a potential relationship between the altered amino acid composition of bile and the reduced number of telocytes in the gallbladder muscle wall in cholelithiasis.

The accuracy of serum osmolarity calculation in small children.

Background: Serum osmolality can be measured (Omeas) or calculated (Ocal). Many formulas for Ocal have been already published, but data regarding the most accurate equation in small babies is not available. Thus, we aim to compare Omeas and Ocal obtained by different formulas in newborns and small children. Methods: The study included 280 serum samples taken from children, from the first day of life to 2 years (mean age 8.2 ± 7.6 months) treated in the University Children's Hospital in Krakow. The serum osmolality was measured by osmometer and calculated by 8 common formulas. Results: The mean value of Omeas (2 8 5 .8 ± 5 .1 mOsm/kgH2O) was significantly different as compared to the mean values of Ocal (p< 0.01) for all formulas, except Ocal obtained by the formula: 1.86*(N a + K) +1.15*Glu + Urea + 14. According to Bland-Altman analysis, this formula showed the best performance for estimating osmolality. In children under 3 months of life Passing-Bablok regression indicated both systematic and proportional error for results obtained by each formula compared to the measured values. Conclusions: To calculate osmolarity in children aged between 3 months and 2 years old the following equation: 1 .86*(N a + K) + 1.1 5*G lu+ U rea+ 14 might be used, whereas serum osmolality in children up to 3 month of life should be measured.

Age-related decrease in serum dihydrotestosterone concentration is accompanied by impaired vascular status.

INTRODUCTION: The effect of androgens on the cardiovascular system in humans is ambiguous. Moreover, still little is known about the effects of the most potent androgen, dihydrotestosterone, on arterial stiffness and endothelial function. The aim of this study was to evaluate whether age-dependent alterations in serum concentration of dihydrotestosterone and its circulating metabolite are accompanied by changes in endothelial function and arterial stiffness. METHODS: In 12 young and 11 older men, basal serum concentrations of testosterone, dehydroepiandrosterone sulfate (DHAE-S), androstenedione (AE), dihydrotestosterone (DHT) and androstanediol glucuronide (ADG) were analyzed in relation to vascular status including cIMT - carotid intima media thickness, cAI - central augmentation index, crPWV - carotid radial pulse wave velocity, SI - stiffness index, endothelial and inflammatory markers. RESULTS: Although concentration of testosterone was not different between young and older group, it was demonstrated that DHT, DHEA-S, AE and ADG were significantly lower in older men in comparison to young men (p < 0.01). Interestingly the most surprising difference was found for DHT concentration, that was as much as 61 % lower in aged men that displayed significantly higher values of cIMT, AI, crPWV and SI (p < 10-4), suggestive of arterial stiffness. Furthermore, DHT was negatively correlated to all arterial wall parameters (cAI, crPWV, SI and cIMT), c-reactive protein (CRP) and hyaluronic acid (HA) concentration, as well as positively correlated to markers of endothelial function (MNA and 6-keto-PGF1α) in all studied individuals (n = 23). CONCLUSIONS: We have shown that ageing leads to a significant decrease in DHT concentration that is accompanied by impaired arterial wall characteristics and worsened endothelial function. Therefore more attention should be paid to the DHT, DHEA-S and ADG concentrations as a biomarkers for vascular dysfunction in ageing men.

The risk of essential fatty acid insufficiency in patients with inflammatory bowel diseases: fatty acid profile of phospholipids in serum and in colon biopsy specimen.

Introduction: The aim of the study was to address the fatty acid (FA) status and its relationship with disease activity in patients with inflammatory bowel disease (IBD). Methods: FA levels of the phospholipid fraction in serum and a colon biopsy specimen were measured in 17 patients with IBD. Results: A negative correlation between the histological activity of inflammation of the disease and the ratio of polyunsaturated FAs/no polyunsaturated FAs was observed. Moreover, the level of that ratio was lower in patients with IBDs as compared to controls. Conclusions: The FA profile in serum and in a colon biopsy specimen in patients with IBD is characteristic for essential fatty acid insufficiency.

Monitoring of treatment with L-asparaginase in children with acute lymphoblastic leukaemia, with a focus on silent inactivation and its influence on the treatment outcome.

Introduction: The aim of the study was to analyse the frequency of silent inactivation and allergic reaction to asparaginase (ASP) and its impact on treatment results in patients with lymphoblastic leukaemia. Material and methods: Seventy patients with acute lymphoblastic leukaemia treated with ASP were enrolled in the study. Asparaginase activity was monitored. The patients were switched to another ASP formulation after allergy or inactivation. The treatment results were analysed. Results: Silent inactivation of native E. coli ASP was diagnosed in 5 patients (7%) and allergy in 34 patients (49%), and these patients were switched to pegylated ASP (PEG-ASP). Silent inactivation of PEG-ASP occurred in 8 patients (23%) and allergy in 6 patients (17%). Eight children continued therapy with Erwinase, and 4 did not switch to Erwinase after inactivation of PEG-ASP. Allergy to Erwinase occurred in 2 patients (22%); there was no inactivation. No significant differences in outcome were found between the groups of patients with and without allergy or silent inactivation of ASP. Due to regular monitoring and switching to other ASP preparations after allergy or silent inactivation, therapeutic activity was ensured in almost all patients. Conclusions: Monitoring of ASP activity is crucial to recognize silent inactivation and to guarantee treatment effectiveness by switching to other ASP preparations.

Evaluation of interleukin-1 beta and the ratio of interleukin-1 beta to interleukin-1 receptor antagonist in gingival crevicular fluid during orthodontic canine retraction.

BACKGROUND: Orthodontic tooth movement (OTM) is a complex phenomenon mediated by cytokines, of which interleukin-1 beta (IL­1ß) is potently involved in the remodeling of the periodontal ligament (PDL) and bone. Whether the pattern of IL­1ß release differs at the sides of tension and compression is not yet clarified. OBJECTIVES: The aim of the present study was to evaluate the level of IL­1ß and the ratio of IL­1ß to interleukin-1 receptor antagonist (IL­1RA) in gingival crevicular fluid (GCF) at the tension and compression sides during orthodontic canine retraction. MATERIAL AND METHODS: Seventeen patients scheduled for orthodontic treatment with bilateral extraction of maxillary first premolars and canine retraction were enrolled. Tooth 2.3 was retracted, teeth 1.3 and 3.3 served as controls. Gingival crevicular fluid samples were collected from the tension and compression sides of each tooth at baseline (before the 1st activation - day 0) and at days 2 and 7, and then again before the 2nd activation (day 28) and at days 30 and 35. The levels of IL­1ß and IL­RA were evaluated with the enzyme-linked immunosorbent assay (ELISA). RESULTS: After the 1st activation, a statistically significant increase in the level of IL­1ß was observed at teeth 2.3 (p < 0.03 mesially and p < 0.05 distally) and 1.3 (p < 0.05 mesially and distally), both at the tension and compression sides. The 2nd activation resulted in a gradual increase in the IL­1ß level at both canines; however, statistical significance was reached only for tooth 2.3 (p < 0.05 mesially and p < 0.02 distally). In terms of the IL­1ß/IL­1RA ratio, a significant increase was observed only at the compression side of the experimental tooth (p < 0.01). CONCLUSIONS: An increase in the IL­1ß level in GCF was observed both at the tension and compression sides of the actively retracted canine 2.3 as well as the contralateral canine 1.3; a significant rise in the IL­1ß/IL­1RA ratio was noted only at the compression side of the experimental tooth 2.3, indicating the zone of active bone resorption.

Amino acids profile in girls with Turner syndrome during growth hormone therapy.

INTRODUCTION: The influence of growth hormone (GH) treatment on amino acids (AAs) profile in patients with Turner syndrome (TS) was investigated. MATERIAL AND METHODS: The study group included girls with TS: treated with GH (GH+) and girls with no GH treatment (GH-). The control group consisted of healthy girls. Free plasma AAs were measured by the LC/MS/MS. RESULTS: The plasma concentrations of glutamine, threonine were significantly higher in group GH+ than in group GH- (p < 0.05). In group GH- the values of glutamine, alanine, isoleucine, glutamic acid were significantly different than in the control (p < 0.05-p < 0.008). CONCLUSION: AAs profile in girls with TS might be characteristic for the disease but also depends on GH treatment.

Newborns bilirubin concentration determined by different methods in relation to hematocrit and albumin level.

BACKGROUND: Monitoring of bilirubin is essential during early neonatal life. Bilirubin in high concentration is toxic to the brain and might cause irreversible neurological damage. Several different methods for bilirubin determination are available nowadays, but inconsistent results may be obtained. The study aimed to compare dry chemistry methods with vanadate oxidation method for bilirubin determination in relation to hematocrit and albumin level in neonates and infants. METHODS: The study included 98 consecutive serum samples from newborns and infants (47 boys and 51 girls, mean age 19 ± 15 days) treated in the University Children's Hospital in Krakow. Total bilirubin (TBil) and neonatal bilirubin (NBil) concentration were measured by dry chemistry analyser (Vitros 4600, Ortho Clinical Diagnostics Inc.). Total bilirubin (TBilV) was also measured using vanadate oxidation method (Cormay, Poland). Albumin concentration and blood morphology have been routinely determined in all children. RESULTS: No significant differences between the mean value of NBil (69.00 ± 67.76 µmol/L), TBil (81.26 ± 70.13 µmol/L) and TBilV (75.90 ± 60.62 µmol/L) were noticed. High coefficient correlation between NBil and TBil as well as between NBil and TBilV were noticed (Pearson's analysis, r = 0.99, r = 0.97, respectively; p < 0.0001 in both cases). There was a positive correlation between the difference (TBilV - NBil) and hematocrit (p < 0.009, r = 0.2664). CONCLUSIONS: In newborns and infants the same method for bilirubin determination should be used when the concentration of bilirubin is monitored. When using vanadate oxidation method for bilirubin determination, hematocrit value should be taken into account when results are interpreted.

Circulating chemerin level may be associated with early vascular pathology in obese children without overt arterial hypertension - preliminary results.

Background Elevated chemerin level is observed in patients with arterial hypertension. The aim of the study was to determine the relationship between chemerin level, and parameters of blood pressure and arterial stiffness in children and adolescents with obesity but without arterial hypertension. Methods In 23 children with obesity (13 girls, mean age 9.3, SD 1.9, mean BMI SDS 3.9, SD 1.7) 24 h ABPM (Spacelabs 90,217, USA), common carotids and abdominal aorta intima media thickness measurements (Voluson 730, GE Medical System 8.5 and 3.5 MHz probes), body composition analysis (Tanita BC 418 S MA, Tokyo, Japan) were performed. Glucose, triglycerides, total, LDL and HDL cholesterol, liver enzymes, uric acid, creatinine, sodium, insulin and chemerin levels were assessed in blood sample taken after a 12-h fasting period. Results There was a significant correlation of circulating chemerin level with systolic blood pressure load in ABPM (r=0.5, p<0.05). Conclusion Elevated chemerin level may be associated with increased systolic blood pressure in obese children.

Metabolic Fingerprint of Turner Syndrome.

Girls with Turner syndrome (TS) are at increased risk of developing insulin resistance and coronary artery disease as a result of hypertension and obesity frequently seen in these patients. On the other hand, it is known that obesity is associated with increased serum levels of branched-chain amino acids (BCAAs: valine; leucine and isoleucine) and aromatic amino acids. The aim of the study is to compare the metabolic fingerprint of girls with TS to the metabolic fingerprint of girls with obesity. Metabolic fingerprinting using an untargeted metabolomic approach was examined in plasma from 46 girls with TS (study group) and 22 age-matched girls with obesity (control group). The mean values of BCAAs, methionine, phenylalanine, lysine, tryptophan, histidine, tyrosine, alanine and ornithine were significantly lower in the study group than in the control (p from 0.0025 to <0.000001). Strong significant correlation between BCAAs, phenylalanine, arginine, tyrosine, glutamic acid, citrulline and alanine, and body mass index expressed as standard deviation score BMI-SDS in the patients with obesity (p from 0.049 to 0.0005) was found. In contrast; there was no correlation between these amino acids and BMI-SDS in the girls with TS. It is suggested that obesity in patients with TS is not associated with altered amino acids metabolism.

Intravenous, Perioperatively Administered Lidocaine Regulates Serum Pain Modulators' Concentrations in Children Undergoing Spinal Surgery.

OBJECTIVES: We analyzed the influence of perioperative, intravenous (i.v.) lidocaine infusion as a part of multimodal anesthesia on concentrations of selected pain modulators. DESIGN: An observational study. SETTING: University Children's Hospital in Cracow, Poland, from May 2015 to May 2018. SUBJECTS: Forty-four children undergoing extensive spinal surgery, divided into two groups after surgery: the study group (N = 23), anesthetized generally with lidocaine as a co-analgesic, and the control group (N = 22), anesthetized generally without lidocaine. METHODS: We assessed proinflammatory mediators like neuron growth factor (NGF), high mobility group box 1 (HMGB1), interleukin 6 (IL-6), and FOS protein before, immediately after, six hours and 12-15 hours after surgery. We evaluated pain intensity at corresponding time points using a 10-point numerical/graphical scale. RESULTS: We observed that children in the lidocaine group had reduced pain intensity in the resting state and during movement until six hours after surgery when compared with controls. We found lower NGF concentrations in the lidocaine group vs controls only at six hours after surgery. Mean HMGB1 concentrations during the postoperative period in the study group were relatively stable, whereas we observed significant increases at six hours after surgery and a slight decrease at 12-15 hours after surgery in the control group. IL-6 concentrations at six hours were lower in lidocaine patients when compared with controls. We noted a negative correlation between HMGB1, NGF, Il-6, and lidocaine concentrations after surgery. We did not find any differences in FOS protein concentrations between the groups. CONCLUSIONS: Our findings suggest that intraoperative and postoperative i.v. lidocaine administration as a part of multimodal anesthesia may reduce inflammatory-dependent postoperative pain intensity.

Effect of intravenous, perioperative-administered lidocaine on serum levels of endocannabinoids and related N-acylethanolamines in children.

BACKGROUND: Endocannabinoids and N-acylethanolamines (NAEs) are compounds that play a significant role in nociception. The promising therapeutic opportunities in postoperative pain management are connected with intra-venous (i.v.) lidocaine administration as a part of multimodal analgesia. Therefore, we analyzed the influence of perioperative, i.v. lidocaine infusion in children on postoperative serum concentrations of endocannabinoids and NAEs. METHODS: Forty-four children undergoing extensive spinal surgery were divided into two groups: the lidocaine group (LG; N.=23), anesthetized generally with lidocaine as a co-analgesic, and the non-lidocaine group (NLG; N.=21), anesthetized generally without lidocaine. We also recruited 23 healthy age- and gender-matched children to the control group. Blood samples were collected before surgery, immediately after surgery, at six hours, and following morning after surgery, while in healthy children we collected blood samples only once. The serum concentrations of endocannabinoids (anandamide [AEA] and 2-arachidonyl glycerol [2-AG]) and NAEs (palmitoylethanolamide [PEA] and oleoylethanolamide [OEA]) were quantified by ultra-high-performance liquid chromatography-mass spectrometry. RESULTS: The concentrations of measured compounds were comparable in controls and in patients before surgery (all P>0.05). During the postoperative period, we found significantly higher AEA and lower 2-AG concentrations in the LG when compared to the NLG. The highest concentration of PEA was observed in LG patients six hours after the operation and, at that time it was significantly elevated when compared to the NLG (P=0.0003). CONCLUSIONS: Perioperative, i.v. lidocaine administration influences postoperative serum concentrations of endocannabinoids and NAEs in children.

Characteristics of amino acid profiles and incretin hormones in patients with gallstone disease: a pilot study.

INTRODUCTION: Gallstone disease is associated with insulin resistance, type 2 diabetes mellitus, and increased risk of incident ischemic heart disease. It is known that the profile of branched­chain amino acids (BCAAs) is altered in cardiac diseases as well as metabolic diseases, such as diabetes and obesity. The role of BCAAs in gallstone disease is still not known. OBJECTIVES: The aim of this study was to evaluate the concentration of essential amino acids and incretin hormones in patients with cholecystolithiasis. PATIENTS AND METHODS: The study included 31 patients with cholecystolithiasis and 25 gallstone­free controls. The levels of free exogenous and endogenous amino acids, bile acids, glucagon­like peptide 1, glucose­dependent insulinotropic polypeptide, ghrelin, C-peptide, and insulin were measured in the fasting state and 1 hour after consumption of a 300­kcal mixed meal. RESULTS: The mean fasting and postprandial levels of valine, isoleucine, leucine, and lysine were higher in the study group than in controls (all P.

Impact of Intravenous, Perioperative-Administrated Lidocaine on Postoperative Serum Levels of Endogenous Opioids in Children.

BACKGROUND: Endogenous opioids are neuropeptides involved in pain-relieving processes. In the periphery, they are synthesised and stored in cells of the immune system. OBJECTIVE: In the current study, we describe the influence of perioperative, intravenous (i.v.) lidocaine infusion in children on postoperative, serum endogenous opioid concentrations in children. METHODS: Forty-four children undergoing major spinal surgery were enrolled in the cohort study. They were divided into two groups: group A (n = 21) generally anesthetised with fentanyl, propofol, rocuronium, a mixture of oxygen/air/sevoflurane and with analgetics and co-analgetics: morphine, acetaminophen, metamizole, gabapentin, dexamethason and group B (n = 23) where, in addition to the above-described general anesthesia, patients were given i.v. lidocaine as a co-analgesic. We also recruited 20 healthy age- and gender-matched children (group C). We measured endogenous opioid levels in serum using immunoenzymatic methods. We evaluated postoperative pain intensity using a numerical or visual pain scale and demand for morphine. RESULTS: The levels of measured endogenous opioids were similar in the control and in the studied groups before surgery. We noted that group B patients had lower pain intensity when compared to group A subjects. In group B, the elevated serum concentrations of ß-endorphin, enkephalin and dynorphin in the postoperative period were reported. We also observed that the levels of endogenous opioids negatively correlated with morphine requirements and positively correlated with lidocaine concentration. CONCLUSION: Multidrug pain management including lidocaine seems to be more efficient than models without lidocaine. The endogenous opioid system should be considered as a novel target for pain relief therapy in children.

Composition of tissue fatty acids of phospholipids depends on tumor localization and disease progression in colorectal patients.

OBJECTIVES: Fatty acids play a role in development and progression of colon cancer. The aim of this study was to assess the relation between tissue fatty acids (saturated fatty acids, unsaturated fatty acids, the ratio of C18 to C18:1 - index of fatty acids saturation, SI), colorectal tumor localization and disease progression. METHODS AND RESULTS: Total of 49 patients (14 with proximal colon, 13 with distal colon and 22 with rectal tumor localization) were studied. One year after surgery 24 patients had the disease progression. Tissue levels of saturated fatty acids and unsaturated fatty acids were measured before surgery by gas-chromatography. These fatty acids were determined in cancerous tissue (CA) and non-cancerous tissue (NCA). The most significant differences in the mean values of fatty acids of phospholipids between CA and NCA in patients with proximal tumor localization were noted. The mean value of C18 was significantly lower while C18:1 was significantly higher in CA as compared to NCA in patients without disease progression (p<0.02; p<0.03; respectively). SI was significantly lower in CA as compared to NCA only in patients without disease progression (p<0.02). CONCLUSION: Fatty acids of tissue phospholipids' fraction, as well as SI, strongly depend on tumor localization and might be useful as potential markers of the disease progression in colorectal cancer patients.

Sclerostin and its significance for children and adolescents with type 1 diabetes mellitus (T1D).

INTRODUCTION: Recent studies have shown that sclerostin, which is a negative regulator of bone formation, could play an important role in the crosstalk between bone and glucose metabolism. The role of sclerostin and its link with glucose homeostasis in type 1 diabetes mellitus (T1D) has not been yet studied extensively in children. The aim of this study was to assess sclerostin and its relationship between other bone and fat related factors as well as glucose metabolism in children and adolescents with T1D in comparison to their healthy peers. METHODS: Forty patients with T1D, 18 girls, mean age 12.3 ±â€¯4.7 yrs, and 28 healthy as controls (13.1 ±â€¯4.2 yrs), sex and Tanner stage-matched were included into the study. Fasting blood samples for measurement of sclerostin, osteocalcin (OC), leptin, adiponectin, vitamin D, fasting glucose, lipid profile, HbA1c, and C-peptide were taken at 8.00 AM. RESULTS: Sclerostin levels were significantly higher in patients with T1D than in the control group (p = 0.04) without significant differences between genders. Pearson correlation coefficients revealed a positive association between serum sclerostin levels and leptin OC (r = 0.59, p < 0.001) and a negative correlation between serum sclerostin levels and leptin (r = -0.32, p = 0.02) in all of the subjects and no significant correlations between sclerostin and adiponectin, 25(OH)D3, nor lipids. In the group of T1D patients a strong positive association between serum sclerostin levels and OC (r = 0.62, p < 0.001), and a negative association between serum sclerostin levels and HbA1c and leptin levels (r = -0.33, p = 0.04; r = -0.33, p = 0.03, respectively) were found. These associations were significant also after adjusting the analysis to the age, SDS-BMI and Tanner staging. In the healthy group after adjustment to age, SDS-BMI and Tanner stage, a negative correlation between sclerostin and C-peptide (r = -0.79, p = 0.02) was found. CONCLUSIONS: Our data suggest a possible relationship between sclerostin and glucose metabolism in children and adolescents with T1D. It would be worth to investigate if an increase in sclerostin levels could present as a potential cause of the reduction of bone formation in T1D. Both bone-derived OC as well as fat-derived leptin seems to possibly modulate the participation of sclerostin in metabolic regulation in T1D.

Sclerostin and its association with insulin resistance in children and adolescents.

INTRODUCTION: Recent studies have shown that sclerostin, which is mainly known as a negative regulator of bone formation, could play an important role in the crosstalk between bone and glucose metabolism. The aim of this study was to investigate the relationship between sclerostin, other bone and fat related factors as osteocalcin (OC), Receptor Activator of Nuclear Factor NF-қB ligand (RANKL), leptin and adiponectin with glucose metabolism and insulin action in children and adolescents with obesity compared with healthy children and adolescents. METHODS: Fifty-five obese children and adolescents, a mean age of 13.2 ±â€¯3.4 yrs., BMI 28.89 ±â€¯5.5 kg/m2, and 26 healthy controls (mean age 13.0 ±â€¯4.3 yrs., BMI 19.96 ±â€¯3.1 kg/m2), sex-, and Tanner stage-matched were included into the study. Fasting blood samples for measurement of sclerostin, glucose, lipid profile, HbA1c, C-peptide, OC, RANKL, leptin and adiponectin, and vitamin D were taken at 8.00 AM. RESULTS: Sclerostin, osteocalcin, RANKL, and adiponectin levels did not differ between obese patients and the control group. Leptin and fasting insulin levels were significantly higher in obese subjects compared with controls (p < 0.01, p = 0.01, respectively). A positive correlation between sclerostin and OC (r = 0.417, p = 0.027) and negative correlations between sclerostin and HOMA-IR and between sclerostin and age (r = -0.24, p = 0.045, r = -0.23, p = 0.037, respectively) were found in all of the subjects. Sclerostin did not correlate with HbA1c, lipids, RANKL and fat-derived leptin and adiponectin. Partial correlation analysis adjusted for age, SDS-BMI and Tanner staging only revealed a negative correlation between sclerostin and HOMA-IR (r = -0.3, p = 0.01). In obese patients this correlation was stronger than in the whole group (r = -0.39, p = 0.005). Moreover, a negative correlation between sclerostin and insulin was found in obese patients (r = -0.39, p = 0.006). In the healthy cohort, sclerostin had a negative correlation only with C-peptide (r = -0.79, p = 0.02). CONCLUSIONS: Sclerostin could play an important role in the regulation of glucose metabolism in children and adolescents, regardless of other fat and bone-derived factors. In obese young patients it's action could be associated with decreasing insulin resistance.

Fatty acids profile in patients after heart or renal transplantation who developed metabolic complications.

PURPOSE: Diabetes mellitus and hyperlipidemia are frequently observed after organ transplantation. It is known that in these disorders the fatty acid metabolism is impaired. The aim of this study was to compare the fatty acid profile in the heart and renal transplant recipients who developed metabolic disorders since there is no such research available. MATERIALS AND METHODS: The study included 55 patients treated with tacrolimus (Tac) after heart (n = 14; mean age: 60.4 ± 9.1) or renal (n = 41; mean age: 51 ± 13) transplantation. Diabetes and hyperlipidemia was present in 35.7% and 28.5% of heart transplant recipients, and 19.5% and 41% of renal transplant recipients. Concentrations of fatty acid in phospholipids fraction in serum were measured by gas chromatography. RESULTS: The concentration of C20:5 fatty acid was lower in heart transplant recipients, as compared to renal transplant recipients (p = 0.001), whereas the level of C20+C18:3 fatty acid and the ratio of n-6/n-3 was higher (p = 0.01; p = 0.03, respectively). The observed differences were not related to metabolic disorders. Negative correlation between C16:1 and eGFR was seen in heart transplant recipients (p = 001). In renal transplant recipients with metabolic disorders, the concentration of C20:5 was correlated positively whereas the n-6/n-3 ratio was correlated negatively with eGFR (p < 0.001, p = 0.01, respectively). Hyperlipidemic renal transplant recipients had higher concentration of C20:2 (p = 0.02), C20:4 (p = 0.05), n-6 (0.04) and total fatty acid (p = 0.01) than patients without metabolic disorders. CONCLUSION: The fatty acid profile differs depending on the transplanted organ, but the differences are not related to the metabolic disorders. The role of fatty acid in kidney function varies between heart transplant recipients and renal transplant recipients and depends on type of fatty acid.