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Introduction: Our study aimed to investigate the effect of zonisamide (ZNS) on bone metabolism in the rat model. Methods: Eight-week-old rats were divided into four groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+ZNS) and the sham-operated control group (SHAM+ZNS) received SLD enriched with ZNS for 12 weeks. Bone marker concentrations in serum of receptor activator of nuclear factor kappa B ligand, PINP, and osteoprotegerin, and the levels of sclerostin and bone alkaline phosphatase in bone homogenate, were measured using an enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The femurs were used for biomechanical testing. Results: We found a statistically significant reduction in BMD and biomechanical strength 12 weeks after orchidectomy of the rats (ORX). After ZNS administration to orchidectomized rats (ORX+ZNS) and the sham-operated control rats (SHAM+ZNS), there were no statistically significant changes in BMD, bone turnover markers, or biomechanical properties as compared with the ORX group and SHAM group. Conclusions: The results suggest that administration of ZNS to rats exerts no negative effect on BMD, bone metabolism markers, or biomechanical properties. [ABSTRACT FROM AUTHOR]

Aim: The objective of this study was to evaluate off-label high-dose ceftazidime population pharmacokinetics in cancer patients with suspected or proven extensively drug-resistant (XDR) Pseudomonas aeruginosa infections and then to compare the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target after standard and off-label high-dose regimens using population model-based simulations. A further aim was to clinically observe the occurrence of adverse effects during the off-label high-dose ceftazidime treatment. Methods: In patients treated with off-label high-dose ceftazidime (3 g every 6 h), blood samples were collected and ceftazidime serum levels measured using LC–MS/ MS. A pharmacokinetic population model was developed using a nonlinear mixedeffects modelling approach and Monte Carlo simulations were then used to compare standard and high-dose regimens for PK/PD target attainment. Results: A total of 14 cancer patients with serious infection suspected of XDR P. aeruginosa aetiology were eligible for PK analysis. XDR P. aeruginosa was confirmed in 10 patients as the causative pathogen. Population ceftazidime volume of distribution was 13.23 L, while clearance started at the baseline of 1.48 L/h and increased by 0.0076 L/h with each 1 mL/min/1.73 m² of eGFR. High-dose regimen showed significantly higher probability of target attainment (i.e., 86% vs. 56% at MIC of 32 mg/L). This was translated into a very low mortality rate of 20%. Only one case of reversible neurological impairment was observed. Conclusion: We proved the superiority of the ceftazidime off-label high-dose regimen in PK/PD target attainment with very low occurrence of adverse effects. The off-label high-dose regimen should be used to optimize treatment of XDR P. aeruginosa infections. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to compare clinical outcomes of very low birth weight (VLBW) infants with 25-hydroxy vitamin D [25(OH)D] levels <25 nmol/l in umbilical cord blood versus VLBW infants with 25(OH)D levels in cord blood >25 nmol/l. The secondary objective was to evaluate umbilical cord vitamin D as a risk factor for respiratory distress syndrome (RDS) in preterm infants. We examined 25(OH)D levels in umbilical cord blood and in infants' serum at discharge from the neonatal intensive care unit. We evaluated the associations between severe vitamin D deficiency and various laboratory findings and clinical outcomes. Eighty one infants with birth weight less than 1500 g met the entry criteria for this study and were divided to groups according to umbilical cord blood vitamin D [Group A: 25(OH)D < 25 nmol/l; 10 ng/ml and Group B: 25(OH)D > 25 nmol/l; 10 ng/ml]. Overall, 81.5% of the infants had a 25(OH)D level <50 nmol/L and 44.4% had a level <25 nmol/L. The laboratory findings and the subsequent clinical outcomes were comparable in infants in both groups (non-significant difference). Only the infants in the 25(OH)D 25 nmol/L group had a lower calcium in urine at age 28 d (p=.0272). In addition, we found in this study that umbilical cord vitamin D level does not lead to a higher or lower risk of RDS (odds ratio 1.044; 95% confidence interval 0.349–0.88; p=.0771). In our prospective cohort study, we found no significant association between vitamin D status and selected clinical outcomes when using a cut-off of 25 nmol/l (severe vitamin D deficiency) in preterm infants. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate vitamin D status in mothers and their very low birth weight infants (VLBW) at birth (umbilical cord blood) and at discharge with currently recommended supplementation of vitamin D.Methods: Ninety-four infants with birth weight less than 1500 g completed the study. The total daily vitamin D intake was 800-1000 IU. We examined 25-hydroxyvitamin-D [25(OH)D] levels in maternal serum before labor, in cord blood, and in infants' serum at discharge.Results: Median (IQR) serum 25(OH)D was 21 (14-36) nmol/l [8 (6-15) ng/ml] in cord blood, and 46 (37-60) nmol/l [18 (15-24) ng/ml] at discharge. Serum 25(OH)D was <50 nmol/L in 71.3% of mothers, in 91.5% of cord blood samples, and in almost 60% of preterm newborns at discharge (after 8 weeks of supplementation). Serum 25(OH)D was <75 nmol/L in 88.3% of mothers, in 97.9% of cord blood samples, and in 91.4% of preterm newborns at discharge.Conclusions: In our cohort, we found that due to the very high prevalence of 25(OH)D deficiency among mothers, the current generally recommended dose of vitamin D (800-1000 IU per day) for VLBW infants was unable to improve vitamin D levels above the desired 50 or even 75 nmol/L before discharge. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this pilot study was to estimate physiological parathyroid hormone (PTH) levels and their relationship with bone metabolism parameters in otherwise healthy preterm newborns with birth weight 1000-1500 g. Methods: PTH, 25(OH)D, S-Ca, S-P, and ALP were analysed from blood samples obtained from 20 preterm infants once a week up to the 36th gestational week. Results: Of the total 134 examined serum samples for PTH levels, the estimated range was 1.6-9.3 pmol/l (15.1-87.7 pg/ml). No statistically significant correlation of PTH level with that of S-Ca, S-P, or ALP was observed, except for the 56th day of life (p = .03; Rho = 0.76; n = 8). From the second month of life, there was a statistically significant relationship only between PTH and 25(OH)D (Rho = -0.71, p ≤ .0001). In our cohort, vitamin D deficiency (20 ng/ml) occurred in 75% at birth and at 30% in the 36th gestational week. Conclusions: The physiological range indicated by the measurements was close to the reference limits for adults (1-7 pmol/l; 9.4-66 pg/ml). PTH level above this range can be considered as hyperparathyroidism in preterm neonates. [ABSTRACT FROM AUTHOR]

This multicentre study focused on monitoring imatinib mesylate (IMA) trough plasma (Ctrough) and intracellular (IMA Cintrac) concentrations in 228 chronic myelogenous leukaemia patients. The median of measured IMA Ctrough in our patient group was 905.8 ng ml (range: 27.7-4628.1 ng/ml). We found a correlation between IMA Ctrough and alpha 1-acid glycoprotein plasma concentrations ( rS = 0.42; p < 0.001). All other analysed parameters revealed only weak (gender, dose of IMA per kg) or not significant (age, albumin, creatinine plasma concentration or body mass index) impact on measured IMA Ctrough. The IMA Ctrough decreased during the first 6 months and significantly increased later during treatment. The IMA Ctrough at the first month of therapy did not differ between patients with and without an optimal response at the 12th ( p = 0.724) and 18th month ( p = 0.135) of therapy. There were no significant differences in medians of IMA Ctrough between both groups measured during the first year of treatment. The IMA Cintrac during the first month were not different between patients with and without an optimal response at the 6th ( p = 0.273) and the 12th month ( p = 0.193) of therapy. Our data obtained from real life clinical practice did not find a benefit of routine and regular IMA Ctrough nor IMA Cintrac therapeutic drug monitoring in chronic myelogenous leukaemia patients or for subsequent adjustments of the IMA dose based on these results. Moreover, actual alpha 1-acid glycoprotein plasma concentration should be used for proper interpretation of IMA Ctrough results. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Confocal laser scanning endomicroscopy (CLSE) is a diagnostic technology that produces virtual histology of the mucosal layer using fluorescence technique. Fluorescein (FSC) is the most commonly used fluorescence agent. Fluorescence light coming from a horizontal special focal plane is detected during confocal laser endomicroscopy of the gastrointestinal tract. FSC causes intensive yellowish discoloration of tissues, including skin and mucous membranes. This pre-clinical study was aimed to evaluate the tissue distribution and pharmacokinetics of FSC after its intravenous administration., Methods: The study was performed in an adult experimental pig. A reversed-phase high-performance liquid chromatographic method with fluorescence detection was used for the determination of fluorescein in blood plasma and tissue samples., Results and Conclusion: The pharmacokinetic study of fluorescein determined the optimum time interval for diagnostic scanning (5-10 min.) The biodistribution study of fluorescein (aimed on the potential organ accumulation) proved the high concentration in the renal system followed by levels in bile > lung > adipose tissue > all other organs (including gastrointestinal wall) and these were relatively similar to each other. Fluorescein has a significantly low distribution in the brain (contrast with the level in adipose tissue indicates the low ability to penetrate the blood-brain barrier).