Efficacy and Safety of Ketogenic Diet Treatment in Pediatric Patients with Mitochondrial Disease.

Mitochondrial diseases (MDs) are a heterogeneous group of disorders resulting from abnormal mitochondrial function. Currently, there is no causal treatment for MDs. The aim of the study was to assess the effectiveness and safety of the ketogenic diet (KD) in patients with MD and to analyse selected biochemical and clinical parameters evaluating the effectiveness of KD treatment in patients with MDs. A total of 42 paediatric patients were assigned to four groups: group 1-patients with MD in whom KD treatment was started (n = 11); group 2-patients with MD remaining on an ordinary diet (n = 10); group 3-patients without MD in whom KD treatment was initiated (n = 10), group 4-patients without MD on a regular diet (n = 11). Clinical improvement was observed in 9/11 patients with MD treated with KD. Among patients with MD without KD, the clinical condition deteriorated in 7/10 patients, improved in 2/10 patients, and remained unchanged in one patient. Adverse events of KD occurred with a comparable frequency in groups 1 and 3. There was no significant difference in changes in biomarker concentrations over the course of the study among patients treated and untreated with KD.

Immunological markers of drug resistant epilepsy and its response to immunomodulatory therapy with ACTH in children.

INTRODUCTION: Drug-resistant epilepsy in infancy and childhood is a devastating condition, frequently associated with neuropsychiatric comorbidities. West syndrome is one of the most severe epilepsy syndromes. Adrenocorticotropic hormone (ACTH) treatment is recommended in such cases, but its mechanism of action is still unknown. We prospectively observed levels of selected cytokines in order to identify biomarkers of response to ACTH and the potential mechanism of its antiseizure effect. MATERIAL AND METHODS: Fifty-three infants and young children with pharmacoresistant epilepsy receiving ACTH 1-24 were included. There were 2 control groups - children with epilepsy responding to the first medication and children with no history of epilepsy. Blood concentrations of IL-1b, IL-1Ra, IL-6, IL-8, IL-10, TNF-a, IFN-g, MCP-1 and MIP-1a were analyzed at three time points: T0 (before ACTH), T1 (after intensive ACTH treatment) and at T2 (at the end of ACTH withdrawal). The results were correlated with the response to treatment, dose of ACTH and concomitant medications. RESULTS: We found statistically significantly higher concentrations of IL-1, IL-8 and MIP-1a at baseline (T0) in the study group compared to the control groups. ACTH significantly lowered levels of IL-6, IFN-g and MCP from time T0 to T1. This effect was short lasting and no significant changes in cytokine levels were found between T2 and T0. We did not find any differences in immunological markers between the responders and non-responders to ACTH. Our research did not allow us to identify any reliable immunological marker of response to ACTH treatment. We did not observe a positive effect of higher ACTH doses on the response rate in the patients. Our study showed significantly lower concentrations of IL-10 and IFN in the group of patients receiving levetiracetam. The concentration of TNF was higher and the concentration of MIP was lower in the group receiving valproic acid. CONCLUSIONS: Our study indicates that increased levels of IL-1, IL-8 and MIP-1a are associated with drug-resistant epilepsy in infants and young children and might be considered immunological markers. IL-6, IFN-g and MCP-1 take part in the effect of ACTH. Immunological mechanisms seem also to be involved in the mechanism of action of classical antiseizure drugs.

The fibroblast growth factor 21 concentration in children with mitochondrial disease does not depend on the disease stage, but rather on the disease genotype.

ABSTRACT: The fibroblast growth factor 21 (FGF21) is a new biomarker of mitochondrial diseases (MD). FGF21 concentration may be used to define the severity of mitochondrial disease. AIM OF THE STUDY: The study objective was to verify if the FGF21 concentration in paediatric patients with MD was correlated with the disease severity and stage and to assess the correlation between FGF21 levels and the genetic background of MD. MATERIAL AND METHODS: The disease stage in MD subjects was determined on the basis of the International Paediatric Mitochondrial Disease Scale (IPMDS) and the concentrations of FGF21, lactic and pyruvic acids, alanine and creatine kinase in serum were assessed in those patients. RESULTS: The median age of children with MD (n = 32) was 33 months (range: 2-213), in the control group (n = 21) the median age was 42 months (range: 8-202). The concentrations of FGF21, lactic acid and pyruvic acid were higher in MD patients than in the control group. No correlation between the disease severity (IPMDS) and serum FGF21 concentration was found. The FGF21 concentration was higher in patients whose MD resulted from nuclear gene damage (nDNA), median FGF21 = 1022 (84-8873) pg/ml, than in patients with MD resulting from mitochondrial damage (mtDNA), median FGF21 = 736 (188-2906) pg/ml, or with an abnormal variant in the PDHA1 gene, median FGF21 = 58 (25-637) pg/ml. CONCLUSIONS: There is no correlation between the stage of MD and FGF21 level. Higher FGF21 values are seen in patients whose MD results from an abnormal nDNA variant rather than mtDNA damage.

Bone Density, Geometry, and Mass by Peripheral Quantitative Computed Tomography and Bone Turnover Markers in Children with Diabetes Mellitus Type 1.

Background: The type 1 diabetes mellitus (T1DM) is a chronic systemic autoimmune-mediated disease characterised by the insulin deficiency and hyperglycaemia. Its deleterious effect on bones concerns not only bone mass, density, and fracture risk but also may involve the linear growth of long bones. Studies on the lower leg in children with T1DM by pQCT have generated conflicting results, and most of the studies published so far focused only on a selected features of the bone. An additional information about growth, modelling, and remodelling processes can be gathered by the bone turnover marker measurement. The objective of the study was to evaluate bone mineral density, mass, and geometry using peripheral quantitative computed tomography as well as bone turnover markers in the patients with type 1 diabetes mellitus. Material and Methods. Bone mineral density, mass, and geometry on the lower leg using peripheral quantitative computed tomography and serum osteocalcin (OC) and carboxyterminal cross-linked telopeptide of type 1 collagen (CTx) were measured in 35 adolescents with T1DM (15 girls) aged 12.3-17.9 yrs. The results were compared to age- and sex-adjusted reference values for healthy controls. Results: Both sexes reveal lower than zero Z-scores for lower leg 66% total cortical bone cross-sectional area to muscle cross-sectional area ratio (-0.97 ± 1.02, p = 0.002517 and -0.98 ± 1.40, p = 0.007050, respectively) while tibia 4% trabecular bone density Z-score was lowered in boys (-0.67 ± 1.20, p = 0.02259). In boys in Tanner stage 5 bone mass and dimensions were diminished in comparison to Tanner stages 3 and 4, while in girls, such a phenomenon was not observed. Similarly, bone formation and resorption were decreased in boys but not in girls. Consistently, bone turnover markers correlated positively with bone size, dimensions, and strength in boys only. Conclusions: T1DM patients revealed a decreased ratio of cortical bone area/muscle area, reflecting disturbed adaptation of the cortical shaft to the muscle force. When analyzing bone mass and dimensions, boys in Tanner stage 5 diverged from "less-mature" individuals, which may suggest that bone development in these individuals was impaired, affecting all three: mass, size, and strength. Noted in boys, suppressed bone metabolism may result in impairment of bone strength because of inadequate repair of microdamage and accumulation of microfractures.

The Clinical and Biochemical Predictors of Bone Mass in Preterm Infants.

BACKGROUND: Metabolic bone disease of prematurity still occurs in preterm infants, although a significant improvement in neonatal care has been observed in recent decades. Dual-energy X-ray absorptiometry (DXA) is the precise technique for assessing bone mineral content (BMC) in preterm infants, but is not widely available. AIM: To investigate the clinical and biochemical parameters, including bone metabolism markers as potential predictors of BMC, in preterm infants up to 3 months corrected age (CA). MATERIALS AND METHODS: Ca-P homeostasis, iPTH, 25-hydroxyvitamin D, osteocalcin, N-terminal propeptide, cross-linked C-telopeptide and amino-terminal pro C-type natriuretic peptide and the DXA scans were prospectively performed in 184 preterm infants (≤ 34 weeks' gestation) between term age and 3 mo CA. Lower bone mass was defined as BMC below or equal to respective median value for the whole study group, rounded to the nearest whole number. RESULTS: The appropriate quality DXA scans were available for 160 infants (87%) examined at term and for 130 (71%) tested at 3 mo CA. Higher iPTH level was the only independent predictor of lower BMC at term, whereas lower BMC at 3 mo CA was associated both with lower urinary phosphate excretion and higher serum osteocalcin level. ROC analysis showed that iPTH >43.6 pg/mL provided 40% sensitivity and 88% specificity in identification of preterm infants with lower BMC at term. In turn, urinary phosphate excretion (TRP>97% or UP/Cr ≤0.74 mg/mg) and serum osteocalcin >172 ng/mL provided 40% sensitivity and 93% specificity in identification of infants with decreased BMC at 3 mo CA. CONCLUSION: Serum iPTH might to be a simple predictor of reduced BMC in preterm infants at term age, but urinary phosphate excretion and serum osteocalcin might predict reduced BMC at 3 mo CA. These results represent a promising diagnostic tool based on simple, widely available biochemical measurements for bone mass assessment in preterm infants.

Evaluation of the immunoradiometric and electrochemiluminescence method for the measurement of serum insulin in children.

Human insulin is a polypeptide hormone produced, stored, and secreted by the ß-cells in the pancreatic islets of Langerhans. Its secretion is stimulated by an increase of the glucose concentration in circulation. Non-radioactive assays are frequently used in many laboratories to measure hormone concentrations, as an alternative to the traditional "gold standard" radioimmuno- and immunoradiometric assays. The precise and reliable determination of the insulin concentration is an important concern in numerous diagnostic procedures. The aim of this study was to compare two commercially available assays (manual and automated) for measurement of serum insulin concentrations. Aliquots of the 86 randomly selected serum samples were measured by Elecsys Insulin Assay (cobas e411 immunoassay analyzer, Roche Diagnostics GmbH, Mannheim, Germany) and DIAsource INS-IRMA Kit (DIAsource ImmunoAssays S.A., Louvain-la-Neuve, Belgium). Compared assays exhibit good correlation (r = 0.996). Insulin concentrations were on average 4.2 µ IU/mL lower (p < 0.05) with the cobas e411 immunoassay analyzer when compared to those measured with DIAsouce Immunoassay. Our findings suggest that electrochemiluminescence method on the cobas e411 analyzer and manual IRMA method offered by the DIAsource for the serum insulin determination could be considered interchangeable.

Impact of vitamin D supplementation during lactation on vitamin D status and body composition of mother-infant pairs: a MAVID randomized controlled trial.

OBJECTIVE: The optimal vitamin D intake for nursing women is controversial. Deterioration, at least in bone mass, is reported during lactation. This study evaluated whether vitamin D supplementation during lactation enhances the maternal and infant's vitamin D status, bone mass and body composition. DESIGN AND METHODS: After term delivery, 174 healthy mothers were randomized to receive 1200 IU/d (800 IU/d+400 IU/d from multivitamins) or 400 IU/d (placebo+400 IU/d from multivitamins) of cholecalciferol for 6 months while breastfeeding. All infants received 400 IU/d of cholecalciferol. Serum 25-hydroxyvitamin D [25(OH)D], iPTH, calcium, urinary calcium, and densitometry were performed in mother-offspring pairs after delivery, and at 3 and 6 months later. RESULTS: A total of 137 (79%) (n = 70; 1200 IU/d, n = 67; 400 IU/d) completed the study. 25(OH)D was similar in both groups at baseline (13.7 ng/ml vs. 16.1 ng/ml; P = 0.09) and at 3 months (25.7 ng/ml vs. 24.5 ng/ml; P = 0.09), but appeared higher in the 1200 IU/d group at 6 months of supplementation (25.6 ng/ml vs. 23.1 ng/ml; P = 0.009). The prevalence of 25(OH)D <20 ng/ml was comparable between groups at baseline (71% vs. 64%, P = 0.36) but lower in the 1200 IU/d group after 3 months (9% vs. 25%, P = 0.009) and 6 months (14% vs. 30%, P = 0.03). Maternal and infants' iPTH, calciuria, bone mass and body composition as well as infants' 25(OH)D levels were not significantly different between groups during the study. Significant negative correlations were noted between maternal 25(OH)D and fat mass (R =  -0.49, P = 0.00001), android fat mass (R = -0.53, P = 0.00001), and gynoid fat mass (R = -0.43, P = 0.00001) after 6 months of supplementation. CONCLUSIONS: Vitamin D supplementation at a dose of 400 IU/d was not sufficient to maintain 25(OH)D >20 ng/ml in nursing women, while 1200 IU/d appeared more effective, but had no effect on breastfed offspring vitamin D status, or changes in the bone mass and the body composition observed in both during breastfeeding. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506557.

Effect of vitamin D status on pharmacological treatment efficiency: Impact on cost-effective management in medicine.

At least 80% of the whole Polish population, including prepubertal children and adolescents, adults and seniors, are vitamin D deficient, defined as 25(OH)D < 50 nmol/L. 83% of Polish newborns start their lives at the state of vitamin D deficiency because 78% of their mothers are also deficient. It was observed that treating patient vitamin D deficiency to vitamin D status serum 25(OH)D) 75-100 nmol/L increased effectiveness of therapies in infectious diseases (chronic hepatitis C, tuberculosis), osteoporosis, multiple sclerosis, epilepsy, Chronic Kidney Diseases and atopic dermatitis. . For these reasons doctors should take special attention to vitamin D status in patients suffering for these diseases properly implementing recent vitamin D recommendation.

Effect of vitamin D status on pharmacological treatment efficiency: Impact on cost-effective management in medicine.

At least 80% of the whole Polish population, including prepubertal children and adolescents, adults and seniors, are vitamin D deficient, defined as 25(OH)D < 50 nmol/L. 83% of Polish newborns start their lives at the state of vitamin D deficiency because 78% of their mothers are also deficient. It was observed that treating patient vitamin D deficiency to vitamin D status serum 25(OH)D) 75-100 nmol/L increased effectiveness of therapies in infectious diseases (chronic hepatitis C, tuberculosis), osteoporosis, multiple sclerosis, epilepsy, Chronic Kidney Diseases and atopic dermatitis. . For these reasons doctors should take special attension to vitamin D status in patients suffering for these diseases properly implementing recent vitamin D recommendation.

Impact of vitamin D supplementation on markers of bone mineral metabolism in term infants.

UNLABELLED: 25-Hydroxyvitamin D (25OHD) may influence bone turnover. We compared the dynamics of bone markers in 30 infants on vitamin D supplementation (≅550 IU/day) with different degrees of hypovitaminosis D (25OHD <11 ng/ml - deficiency vs. ≥ 11 <20 ng/ml - insufficiency). Baseline and follow-up (after 10 weeks), 25OHD, 1,25-dihydroxyvitamin D (1,25(OH)(2)D), alkaline phosphatase (ALP), PTH, osteocalcin (OC), N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX), and amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) were measured. None of the newborns had craniotabes, hypocalcemia or hyperparathyroidism. The median (Q1;Q3) 25OHD increased from a baseline of 8.45 (7;11.9) ng/ml to 54.6 (34.7;67.3) ng/ml (p<0.001). The baseline 25OHD negatively correlated with total increment of 25OHD (r=-0.54; p=0.002). There were changes in ALP (241 vs. 331 IU; p<0.001), 1,25(OH)(2)D (48 vs. 95.5 pg/ml, p<0.001), OC (88.8 vs. 159.1 ng/ml, p<0.001), PINP (3886 vs. 2409 ng/ml; p<0.001), CTX (1.6 vs. 1.1 ng/ml; p<0.001), and NT-proCNP (75.1 vs. 35.1 pmol/l; p<0.001). Vitamin D deficient infants at baseline, compared to the insufficient group, revealed significantly higher percentage changes for 25OHD (745% vs. 167%, p<0.0001), OC (113% vs. 40%, p<0.05) and 1,25(OH)(2)D (95% vs. 58%, p<0.05). CONCLUSIONS: Vitamin D supplements had little to no impact on markers of bone turnover in term infants in the first few months of life, with the exception of osteocalcin. Ten weeks of cholecalciferol supplementation at a dose of 550 IU/day led to a marked increase of 25OHD concentration. The magnitude of 25OHD increment was inversely related to vitamin D status at baseline. Irrespective of the severity of vitamin D deficiency, a secondary hyperparathyroidism with elevated iPTH, ALP, phosphaturia or hypophosphatemia was not observed in the studied neonates.

Bone metabolism in cholestatic children before and after living-related liver transplantation--a long-term prospective study.

Bone disorders are common in children with end-stage liver diseases, especially those associated with cholestasis. Abnormal hepatocyte function, disordered vitamin D metabolism and calcium-phosphorous homeostasis, malnutrition, and immunosuppressive treatment are potential risk factors of bone tissue pathology before and after transplantation. The aim of the study was to analyze the long-term effect of successful living-related liver transplantation (LRLTx) on skeletal status and bone metabolism in cholestatic children. Eighteen cholestatic children (1.4±0.5yr old; 12 females [F]/6 males [M]) qualified for LRLTx were analyzed; 16 (5F/11M) of them participated in long-term observation (V4). Serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), cross-linked telopeptide of type 1 collagen (CTx), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were assayed before (V0) and 6mo (V1), 12mo (V2), 18mo (V3), and 4.4yr (V4) after LRLTx. Total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD) were measured by dual-energy X-ray absorptiometry (DXA) at the same pattern. Before LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 levels as well as TBBMC and TBBMD were decreased compared with age-matched control group. The mean serum levels of 25(OH)D and 1,25(OH)(2)D were within reference ranges from V0 to V4. After LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 as well as TBBMC and TBBMD reached the age-matched reference values. At V4, the level of P1NP decreased below and the PTH increased above the reference range that coincided with reduced Z-scores of both TBBMC (-1.11±1.24) and TBBMD (-1.00±1.19). P1NP and CTx, both measured at V3, correlated with IGF-I at V2 (R=0.86, p=0.014 and R=0.78, p=0.021, respectively) and PTH at V3 for P1NP and V1 for CTx (R=0.64, p=0.048 and R=0.54, p=0.038, respectively). The TBBMC changes between V0 and V4 correlated with IGF-I (R=0.68, p=0.015) and 1,25(OH)(2)D (R=0.54, p=0.025), both assayed at V1. The change of TBBMC Z-scores between V0 and V4 correlated with P1NP at V1 (R=0.69, p=0.002). The TBBMD changes between V0 and V4 correlated with CTx at V1 (R=0.54, p=0.027) and P1NP change between V0 and V1 (R=0.51, p=0.038). In short-term observation, successful LRLTx led to bone metabolism normalization triggered by probable anabolic action of IGF-I and PTH and manifested by TBBMC and TBBMD increases. In long-term horizon, moderately impaired DXA assessed bone status coincided with disturbances in bone metabolism. Bone metabolism markers, especially P1NP and CTx, appeared to be good predictors of changes in bone status evaluated by DXA.

[Pathologies of calcium-phosphate homeostasis]. / Patologie zwiazane z gospodarka wapniowo-fosforanowa.

The colossal progress in understanding of vitamin D and phosphate metabolism introduces new perspectives in chronic kidney disease (CKD) therapy. Increasing demand for phosphate excretion per nephron triggers the vicious cycle that leads to increase in FGF-23 and PTH and decrease in vitamin D and Klotho. Restriction of dietary phosphate intake (low phosphate diet) and administration of phosphate binder can be regarded as the most important interventions in this case. Because the vicious cycle is likely activated long before hyperphosphatemia occurs during CKD progression, phosphate restriction would have been more effective if started before serum phosphate levels increased, perhaps as soon as serum FGF-23 levels rose. Phosphate restriction alleviates phosphate overload per nephron and can disrupt the vicious cycle: phosphate restriction can reduce serum FGF-23 levels and increase vitamin D, which in turn increase Klotho expression in kidney and parathyroid glands. Inhibitors of rennin-angiotensin system (rosiglitazone, angiotensin-converting enzyme inhibitors) and proper vitamin D supplementation may also up-regulate Klotho expression. Increased Klotho in the kidney may improve FGF-23 sensitivity, which further reduce the amount of FGF-23 required for excreting a given amount of phosphate. Increased Klotho in parathyroid may improve the ability of FGF-23 to suppress PTH. Proper supplementation with vitamin D increase the concentration of substrate for local 1,25(OH)2D synthesis 25(OH)D, which directly suppress PTH, increase Klotho, and decrease FGF-23 by proanabolic action on bone. Improving vitamin D status by inhibition of CYP24A is also under evaluation, as well as antibodies against FGF-23, as modern therapies in CKD.

Vitamin D supplementation and status in infants: a prospective cohort observational study.

OBJECTIVE: Vitamin D status in infants depends on supplementation. We examined the vitamin D status in relation to supplementation dose and scheme in infants. PATIENTS AND METHODS: One hundred thirty-four infants age 6 months and 98 infants age 12 months (drop out 27%) were investigated. Vitamin D intake (diet, supplements), anthropometry, and 25-hydroxyvitamin D (25-OHD) serum concentration at the 6th and 12th months were assessed. RESULTS: Vitamin D intake of 1062 ± 694 IU at the 6th month was not different from that at the 12th month (937 ± 618 IU). Vitamin D intake expressed in international units per kilogram of body weight decreased from 141 ± 80 IU/kg at the 6th month to 93 ± 62 IU/kg at the 12th month (P < 0.0001), which was associated with a reduction in 25-OHD from 43 ± 20 ng/mL to 29 ± 12 ng/mL, respectively (P < 0.0001). In the subgroup of everyday supplemented infants (n = 43), vitamin D intake decreased from 143 ± 88 IU/kg at the 6th month to 118 ± 60 IU/kg at the 12th month (P < 0.05), which coincided with a reduction of 25-OHD from 40 ± 19 ng/mL to 32 ± 13 ng/mL (P < 0.01). In the subgroup with variable supplementation habits (n = 32), vitamin D intake decreased from 146 ± 79 IU/kg to 77 ± 56 IU/kg (P < 0.001), which was associated with a reduction of 25-OHD from 42 ± 21 ng/mL to 25 ± 8 ng/mL (P < 0.0001). 25-OHD concentration change between the 6th and the 12th months negatively correlated with the 25-OHD level assessed at the 6th month (r = -0.82; P < 0.0001). CONCLUSIONS: Vitamin D supplementation of infants should consider their rapid body weight increment. We postulate vitamin D daily dose close to 100 IU/kg body weight as favorable for infants up to age 12 months.

Accelarated skeletal maturation in children with primary hypertension.

It is hypothesized that primary hypertension (PH) is a disorder with origins in childhood linked to, at least in part, aberrations of growth and maturation processes. To evaluate the possible relation between the rate of biological maturity and development of PH, bone age (BA) assessments on the basis of dual x-ray absorptiometry-derived hand scans were performed in 54 newly diagnosed children and adolescents with PH and 54 healthy controls matched for body mass index (BMI), age and sex. Chronological age (CA), body height (in centimeters), body weight (in kilograms), BMI (in kilograms per meter squared), and blood pressure were assessed. Healthy controls had a mean BA of 14.7+/-2.3 years that was not significantly different from their mean CA of 14.2+/-2.1 years. In the PH group, the BA of 16.0+/-2.0 years was higher by 1.9+/-0.9 years compared with their CA of 14.1+/-2.0 years (P<0.0001). The magnitude of acceleration of skeletal maturation (BA-CA) and its prevalence (88.9%) were significantly higher in PH compared with BMI-matched controls (37.0%; chi(2)=31.4; P<0.0001). BA-CA values of PH patients were higher by 1.24 years in normal weight (P<0.0001), 1.80 years in overweight (P<0.01), and 1.40 years in obese (P<0.0001) subgroups of BMI z score-matched controls. Stepwise regression revealed that predictors of blood pressure status from normotension through prehypertension stages 1 and 2 of hypertension were BA-CA (beta=0.530; P<0.0.001), height (beta=-0.379; P<0.01), and CA (beta=0.298; P<0.05; R(2)=0.43). In conclusion, irrespective of BMI, advanced biological maturation should be considered as an independent marker for the development of hypertension.

Stabilizing the urinary activity of fructose-1,6-bisphosphatase with EDTA and mercaptoethanol.

OBJECTIVES: The study aim was to establish conditions for stabilization the activity of fructose-1,6-bisphosphatase (FBP-1) in stored urine. DESIGN AND METHODS: The FBP-1 was determined by the method Kepka et. al in a collected fraction of purified urine. RESULTS: EDTA and mercaptoethanol stabilized FBP-1 activity in stored urine. CONCLUSION: At optimal conditions urine may be stored up to 7 days at a temperature of 4 degrees C.

[Mechanisms of action of anticatabolic drugs used in osteoporosis therapy]. / Mechanizmy dzialania leków antykatabolicznych stosowanych w osteoporozie.

Bone remodeling is essential for skeletal and the whole body health. Imbalance in skeletal turnover, so that bone resorption exceeds bone formation, may lead to reduction in bone strength and increase fractures risk. The main target of anticatabolic therapy is to normalize increased osteoclasts activity and bone turnover. Molecular mechanisms of action of this class of drugs are related with different points in cellular signaling pathways that control osteoclasts differentiation and resorbing activity. These mechanisms are briefly described in our review.

Bone mineral metabolism in children with biliary atresia after living related liver transplantation. Evaluation of selected parameters.

BACKGROUND: Aim of the study was to analyze the effect of living related liver transplantation on selected parameters of bone formation and resorption in children with liver cirrhosis caused by biliary atresia. MATERIAL/METHODS: 20 children (13F/7M) with biliary atresia aged from 6 month to 2.4 years were enrolled into the study 4-9 days before liver transplantation. Osteocalcin, procollagen 1 aminoterminal propeptide, collagen type 1 crosslinked C-telopeptide, parathyroid hormone and metabolites of vitamin D: 25(OH)D3, 1,25(OH)2D3 were measured before, 3, 6 and 12 months after liver transplantation. RESULTS: Three months after living related liver transplantation statistically significant increase of osteocalcin, collagen type 1 crosslinked C-telopeptide, parathyroid hormone and 1,25(OH)2D3 levels were found. We didn't observe further increase of these parameters during the next 9 months after liver transplantation. There was no difference in 25(OH)D3 levels in patients before and after liver transplantation. CONCLUSIONS: In children after successful living related liver transplantation we observed improvement of selected parameters of bone formation and resorption which indicate stimulation of growing processes and mechanisms of bone geometry modelling.

Suramin-induced reciprocal changes in glucose and lactate synthesis in renal tubules contribute to its hyperglycaemic action.

Suramin is the drug of choice for the treatment of African trypanosomiasis and onchocerciasis. It is also tested for its potential use as an anticancer agent and chemosensitizer. As suramin has been reported to induce hyperglycaemia, its effect on glucose formation has been studied in isolated rabbit hepatocytes and kidney-cortex tubules. In contrast to hepatocytes, in kidney-cortex tubules suramin augments glucose production and decreases lactate formation. Suramin-induced changes in intracellular gluconeogenic/glycolytic intermediates indicate a decrease in flux through pyruvate-phosphoenolpyruvate step. Moreover, this compound diminishes pyruvate kinase activity in kidney-cortex cytosolic fraction, while fructose-1,6-bisphosphate ameliorates its inhibitory action. As (i) kidneys are important contributors to the whole body glucose homeostasis and (ii) suramin is known to accumulate in kidney, suramin-induced stimulation of glucose formation in renal tubules might be responsible for hyperglycaemia observed in patients undergoing suramin treatment.