Human Pharmacokinetics of l-3,4-Dihydroxyphenylalanine Studied with Microdialysis

Abstract Background: Intravenous and subcutaneous microdialysis was performed to compare the free concentrations and pharmacokinetics of l-3,4-dihyroxyphenylalanine (l-dopa) in blood and tissue in healthy subjects and in patients with Parkinson disease. Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of l-dopa and 25 mg of benserazide), and the microdialysis was continued for another 210 min. Blood samples were obtained at 30-min intervals. Results: The serum samples gave a significantly higher mean area under the curve (AUC; 491 ± 139 μmol · min/L) than that for intravenous dialysates (235 ± 55.3 μmol · min/L), suggesting a protein binding of 50%. The l-dopa concentrations from the subcutaneous dialysates matched those from the intravenous dialysates, indicating rapid distribution of l-dopa to the tissues. Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free l-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.

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Plasma Level of MMP-10 May Be a Prognostic Marker in Early Stages of Breast Cancer

Journal of Clinical Medicine ◽

10.3390/jcm9124122 ◽

2020 ◽

Vol 9 (12) ◽

pp. 4122

Author(s):

Barbara Maria Piskór ◽

Andrzej Przylipiak ◽

Emilia Dąbrowska ◽

Iwona Sidorkiewicz ◽

Marek Niczyporuk ◽

...

Keyword(s):

Breast Cancer ◽

Area Under The Curve ◽

Disease Stage ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Early Stages ◽

Potential Marker ◽

Breast Cancer Biomarkers ◽

Diagnostic Usefulness ◽

Chemiluminescent Microparticle Immunoassay

Background: Stromelysins are potential breast cancer biomarkers. The aim of the study was to evaluate if plasma levels of selected metalloproteinases (MMPs) (stromelysin-1 (MMP-3) and stromelysin-10 (MMP-10)) and cancer antigen 15-3 (CA 15-3) used separately and in combination demonstrated diagnostic usefulness in breast cancer (BC). Methods: The study group consisted of 120 patients with BC, while the control group included 40 patients with benign breast cancer and 40 healthy individuals. Concentrations of MMP-3 and MMP-10 were determined by enzyme-linked immunosorbent assay; CA 15-3 was determined by chemiluminescent microparticle immunoassay. Results: In the group of patients with BC, the area under the curve (AUC) was significantly higher for all markers (except MMP-3) and all sets of markers. At the earliest disease stage, only MMP-10 had a significantly higher AUC (AUC = 0.8692, p < 0.001). Moreover, MMP-10 had the highest AUC (0.9166) among parameters tested separately. The highest AUC was observed for the combination of MMP-10 + CA 15-3 and MMP-3 + MMP-10 + CA 15-3 in line with disease progression (stage I 0.8884 and 0.8906, stage II 0.9244 and 0.9308, stages III + IV 0.9919 and 0.9944, respectively, p < 0.001 in all cases). Conclusions: The results suggest that MMP-10 could be a potential marker in early stages of BC. Moreover, plasma concentration of MMP-10 and MMP-3 in combination with CA 15-3 may improve diagnosis of this type of cancer.

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Predictive value of the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-neutrophil ratio, and neutrophil-to-monocyte ratio in lupus nephritis

Lupus ◽

10.1177/0961203320929753 ◽

2020 ◽

Vol 29 (9) ◽

pp. 1031-1039

Author(s):

Peng Liu ◽

Peiyuan Li ◽

Zhong Peng ◽

Yazhou Xiang ◽

Chenqi Xia ◽

...

Keyword(s):

Lupus Nephritis ◽

Healthy Subjects ◽

Area Under The Curve ◽

Neutrophil To Lymphocyte Ratio ◽

Control Group ◽

Receiver Operating Characteristic Curves ◽

Lymphocyte Ratio ◽

And Control ◽

First Time

Objective To evaluate the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), and neutrophil-to-monocyte ratio (NMR) as predictors for lupus nephritis (LN) patients without infection or as biomarkers for distinguishing between infection or flare with LN patients. Methods LN patients were divided into three groups: LN without infection, LN with infection, and LN with flare. A total of 57 healthy subjects were enrolled as controls. The differentiation was analyzed between LN without infection and control group, and LN with infection and LN with flare. Correlations among variables were assessed in the LN group without infection. Receiver operating characteristic curves were constructed in two comparable groups. Results NLR, PLR, and MLR were increased significantly in the LN group without infection as compared with those in healthy controls. NLR (area under the curve (AUC): 0.75) and MLR (AUC: 0.79) were useful for distinguishing between LN patients without infection and healthy subjects. In differentiating LN patients without infection from the controls, optimal cutoffs of NLR and MLR were 3.43 (sensitivity: 45.6%, specificity: 96.5%, and overall accuracy: 68.8%) and 0.24 (sensitivity: 75.0%, specificity: 73.7%, and overall accuracy: 73.6%), respectively. In addition, NLR ( r = 0.322, p = 0.011) and PLR ( r = 0.283, p = 0.026) were positively correlated with CRP. Importantly, NLR and NMR were increased while PNR was decreased in the LN group with infection in comparison with those in the LN group with flare. NLR (AUC: 0.80), NMR (AUC: 0.78), and PNR (AUC: 0.74) were useful in differentiating LN patients with infection and flare, and their optimal cutoffs were 4.02 (sensitivity: 82.6%, specificity: 69.6%, and overall accuracy: 75.5%), 12.19 (sensitivity: 80.4%, specificity: 73.9%, and overall accuracy: 77.5%), and 28.26 (sensitivity: 65.2%, specificity: 76.8%, and overall accuracy: 71.6%), respectively. Conclusions We demonstrated, for the first time, that MLR or NMR had the best accuracy in differentiating LN patients without infection from healthy subjects, or differentiating infection from flare in LN patients, respectively. Our results implied that NLR, MLR, PNR, and NMR may be useful biomarkers in predicting LN.

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Disease Severity Is Associated with Alexithymia in Patients with Atopic Dermatitis

Dermatology ◽

10.1159/000507246 ◽

2020 ◽

Vol 236 (4) ◽

pp. 329-335

Author(s):

Andrea Chiricozzi ◽

Maria Esposito ◽

Paolo Gisondi ◽

Mario Valenti ◽

Niccolò Gori ◽

...

Keyword(s):

Atopic Dermatitis ◽

Logistic Regression ◽

Disease Severity ◽

Healthy Subjects ◽

Sleep Disturbances ◽

Rating Scale ◽

Univariate Analysis ◽

Control Group ◽

Predicting Factor ◽

Tas 20

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder that is associated with higher rates of psychological disorders, but limited evidence supported the association with alexithymia, a psychoaffective dysfunction. Objectives: This study was aimed to investigate the occurrence of alexithymia in AD patients, compared to healthy subjects. Methods: This cross-sectional study assessed AD severity by the Eczema Area and Severity Index (EASI) score, sleeplessness and itch by a numeric rating scale (NRS), and alexithymia by the 20-item Toronto Alexithymia Scale (TAS-20) score. The association between disease characteristics and alexithymia was evaluated through several logistic regression models. Results: 202 AD patients and 240 healthy subjects were included in this study. The alexithymic personality trait (TAS-20 ≥51) was more frequently observed among AD patients compared to the control group (62.4% [126/202] vs. 29.2% [70/240], p < 0.0001). In particular, alexithymia (TAS-20 score ≥61) was detected in a significantly higher number of AD patients than in the controls (27.7% [56/202] vs. 7.5% [18/240]; p < 0.0001), whereas borderline alexithymia was detected in 34.6% (70/202) of AD patients compared to 21.7% of healthy controls. Alexithymia was more common among severe AD patients (43.6%) compared to mild AD patients (15.6%) and correlated with itch intensity and sleep disturbances. Among clinical variables, ordered logistic regression analyses revealed disease severity as predictor of alexithymia. Indeed, univariate analysis showed EASI score, sleep NRS, and itch NRS being significantly associated with alexithymia, while a multivariate model identified increased EASI score values as predicting factor. Conclusion:This study described alexithymia in AD patients correlating its occurrence with clinical AD severity markers (EASI score, itch, and sleeplessness) and identifying the increase in EASI score as predicting factor.

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The Cholinomimetic Agent Carbachol Induces Headache in Healthy Subjects

Cephalalgia ◽

10.1111/j.1468-2982.2008.01715.x ◽

2009 ◽

Vol 29 (2) ◽

pp. 258-268 ◽

Cited By ~ 14

Author(s):

HW Schytz ◽

T Wieneckey ◽

PS Oturai ◽

J Olesen ◽

M Ashina

Keyword(s):

Healthy Subjects ◽

Rating Scale ◽

Parasympathetic Nervous System ◽

Superficial Temporal Artery ◽

Area Under The Curve ◽

Temporal Artery ◽

Double Blind ◽

Migraine Pathogenesis ◽

Blind Crossover Study ◽

Double Blind Crossover Study

The parasympathetic nervous system is likely to be involved in migraine pathogenesis. We hypothesized that the cholinomimetic agonist carbachol would induce headache and vasodilation of cephalic and radial arteries. Carbachol (3 μg/kg) or placebo was randomly infused into 12 healthy subjects in a double-blind crossover study. Headache was scored on a verbal rating scale from 0–10. Velocity in the middle cerebral artery (Vmca) and diameter of the superficial temporal artery (STA) and radial artery (RA) were recorded. Nine participants developed headache after carbachol compared with three after placebo. The area under the curve for headache was increased after carbachol compared with placebo both during infusion (0–30 min) ( P = 0.042) and in the postinfusion period (30–90 min) ( P = 0.027). Carbachol infusion caused a drop in Vmca ( P = 0.003) and an increase in STA diameter ( P = 0.006), but no increase in the RA diameter ( P = 0.200). In conclusion, the study demonstrated that carbachol caused headache and dilation of cephalic arteries in healthy subjects.

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Multimodal Balance Training Supported by Rhythmic Auditory Stimuli in Parkinson Disease: Effects in Freezers and Nonfreezers

Physical Therapy ◽

10.1093/ptj/pzaa146 ◽

2020 ◽

Vol 100 (11) ◽

pp. 2023-2034

Author(s):

Tamine T C Capato ◽

Nienke M de Vries ◽

Joanna IntHout ◽

Jordache Ramjith ◽

Egberto R Barbosa ◽

...

Keyword(s):

Parkinson Disease ◽

Mixed Model ◽

Linear Mixed Model ◽

Rating Scale ◽

Balance Training ◽

Auditory Stimuli ◽

Control Group ◽

Multimodal Training ◽

Regular Training

Abstract Objective To fulfill the potential of nonpharmacological interventions for people with Parkinson disease (PD), individually tailored treatment is needed. Multimodal balance training supported by rhythmic auditory stimuli (RAS) can improve balance and gait in people with PD. The purpose of this study was to determine whether both freezers and nonfreezers benefit. Methods A secondary analysis was conducted on a large randomized controlled trial that included 154 patients with PD (Hoehn & Yahr Stages 1–3 while ON-medication) who were assigned randomly to 3 groups: (1) multimodal balance training with RAS delivered by a metronome (RAS-supported multimodal balance training); (2) regular multimodal balance training without rhythmic auditory cues; and (3) a control intervention (involving an educational program). Training was performed for 5 weeks, twice per week. The primary outcome was the Mini-BESTest score directly after the training period. Assessments were performed by a single, masked assessor at baseline, directly postintervention, and after 1-month and 6-month follow-up. Outcomes were analyzed in 1 analysis, and the results were presented separately for freezers and nonfreezers with a linear mixed model, adjusted for baseline Mini-BESTest scores, Unified Parkinson’s Disease Rating Scale scores, and levodopa equivalent dose. Results In both freezers and nonfreezers, both RAS-supported multimodal training and regular training significantly improved the Mini-BESTest scores compared with baseline scores and with the control group scores. The improvement was larger for RAS-supported training compared with regular training, for both freezers and nonfreezers. Only the RAS-supported training group retained the improvements compared with baseline measurements at 6-month follow-up, and this was true for both freezers and nonfreezers. Conclusions RAS-supported multimodal training is effective in improving balance performance in both freezers and nonfreezers. Impact Until this study, it was unknown whether both freezers and nonfreezers could benefit from multimodal balance training. With this information, clinicians who work with people with PD will be better able to apply personalized gait rehabilitation. Lay Summary Adding rhythmic auditory stimuli (RAS) to balance training is beneficial for both freezers and nonfreezers, at least in persons with mild to moderate disease stages. This RAS-supported multimodal training has good potential for a wider clinical implementation with good long-term effects.

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Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis

The Scientific World JOURNAL ◽

10.1155/2017/9320802 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Gheyath Al Gawwam ◽

Inas K. Sharquie

Keyword(s):

Multiple Sclerosis ◽

Area Under The Curve ◽

The Body ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Operating Characteristics ◽

Serum Samples ◽

Elisa Technique ◽

Autoimmune Demyelination ◽

Serum Glutamate

One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS). Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA) is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was1.318±0.543 nmol/ml and that of the controls was0.873±0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC) of 0.738, which was significant (pvalue = 0.001). The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.

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First trimester secreted Frizzled-Related Protein 4 and other adipokine serum concentrations in women developing gestational diabetes mellitus

PLoS ONE ◽

10.1371/journal.pone.0242423 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242423

Author(s):

Joost H. N. Schuitemaker ◽

Rik H. J. Beernink ◽

Arie Franx ◽

Thomas I. F. H. Cremers ◽

Maria P. H. Koster

Keyword(s):

Logistic Regression ◽

Gestational Diabetes ◽

Gestational Age ◽

Area Under The Curve ◽

First Trimester ◽

Multivariate Logistic Regression Model ◽

Control Group ◽

Related Protein ◽

Serum Samples ◽

First Trimester Of Pregnancy

Background The aim of this study was to evaluate whether soluble frizzled-related protein 4 (sFRP4) concentration in the first trimester of pregnancy is individually, or in combination with Leptin, Chemerin and/or Adiponectin, associated with the development of gestational diabetes (GDM). Methods In a nested case-control study, 50 women with GDM who spontaneously conceived and delivered a live-born infant were matched with a total of 100 uncomplicated singleton control pregnancies based on body mass index (± 2 kg/m2), gestational age at sampling (exact day) and maternal age (± 2 years). In serum samples, obtained between 70–90 days gestational age, sFRP4, Chemerin, Leptin and Adiponectin concentrations were determined by ELISA. Statistical comparisons were performed using univariate and multi-variate logistic regression analysis after logarithmic transformation of the concentrations. Discrimination of the models was assessed by the area under the curve (AUC). Results First trimester sFRP4 concentrations were significantly increased in GDM cases (2.04 vs 1.93 ng/ml; p<0.05), just as Chemerin (3.19 vs 3.15 ng/ml; p<0.05) and Leptin (1.44 vs 1.32 ng/ml; p<0.01). Adiponectin concentrations were significantly decreased (2.83 vs 2.94 ng/ml; p<0.01) in GDM cases. Further analysis only showed a weak, though significant, correlation of sFRP4 with Chemerin (R2 = 0.124; p<0.001) and Leptin (R2 = 0.145; p<0.001), and Chemerin with Leptin (R2 = 0.282; p<0.001) in the control group. In a multivariate logistic regression model of these four markers, only Adiponectin showed to be significantly associated with GDM (odds ratio 0.12, 95%CI 0.02–0.68). The AUC of this model was 0.699 (95%CI 0.605–0.793). Conclusion In the first trimester of pregnancy, a multi-marker model with sFRP4, Leptin, Chemerin and Adiponectin is associated with the development of GDM. Therefore, this panel seems to be an interesting candidate to further evaluate for prediction of GDM in a prospective study.

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Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease

Neurology ◽

10.1212/wnl.0000000000004185 ◽

2017 ◽

Vol 89 (5) ◽

pp. 439-444 ◽

Cited By ~ 19

Author(s):

María Sierra ◽

Isabel Martínez-Rodríguez ◽

Pascual Sánchez-Juan ◽

Isabel González-Aramburu ◽

Mikel Jiménez-Alonso ◽

...

Keyword(s):

Parkinson Disease ◽

Rating Scale ◽

Area Under The Curve ◽

Region Of Interest ◽

High Sensitivity ◽

Spect Imaging ◽

Imaging Biomarkers ◽

Asymptomatic Carriers ◽

G2019s Mutation ◽

Dat Spect

Objective:To assess the value of baseline clinical and imaging biomarkers in a cohort of asymptomatic LRRK2 G2019S carriers for predicting conversion to Parkinson disease (PD) at 4 years.Methods:Thirty-two asymptomatic carriers of LRRK2 G2019S mutation underwent baseline and 4-year evaluation including clinical examination (Unified Parkinson's Disease Rating Scale, part III, olfaction University of Pennsylvania Smell Identification Test [UPSIT]) and dopamine transporter (DaT) SPECT (123I-ioflupane). Visual and semiquantitative analysis of images was performed. The specific striatal binding ratio was calculated (striatal region of interest [ROI] − occipital ROI/occipital ROI).Results:Three carriers, asymptomatic at baseline, had converted to PD at 4-year evaluation. Twenty-three participants were fully evaluated. PD converters had lower striatal DaT binding at baseline than nonconverters (p = 0.002). A baseline scan with a ratio of bilateral striatal uptake below 1 predicted conversion to PD within the 4-year period with high sensitivity and specificity (area under the curve 1; p = 0.006). The slope of DaT binding decline between the 2 scans was similar in PD converters and nonconverters. Age-adjusted UPSIT score at baseline and at 4 years was similar in both groups.Conclusions:Semiquantitative DaT-SPECT could be used to predict early conversion to PD in asymptomatic carriers of the LRRK2 G2019S mutation. Rate of conversion to PD at 4 years in this cohort aged ∼64 years was 12%. The slope of DaT binding decline on DaT-SPECT imaging seems to be similar across different stages of the premotor period.

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In Vitro ADME, Preclinical Pharmacokinetics and Prediction of Human Pharmacokinetics of RBx14255, a Novel Ketolide with Pharmacodynamics Against Multidrug-Resistant Bacterial Pathogens

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps30942 ◽

2020 ◽

Vol 23 ◽

pp. 206-219

Author(s):

SAMUEL RAJ VETHAKKANI ◽

Trdib Chaira ◽

Tarani Barman

Keyword(s):

Protein Binding ◽

Plasma Protein Binding ◽

Plasma Protein ◽

Oral Dosage ◽

Absolute Bioavailability ◽

Pharmacokinetic Parameters ◽

Pharmacokinetic Studies ◽

Human Pharmacokinetics ◽

Infection Models

Purpose: The preclinical pharmacokinetic and pharmacodynamic properties of a potent fluoroketolide RBx14255 against Streptococcus pneumoniae and Haemophilus influenzae was compared with telithromycin and human clinical dose was predicted for preclinical development. Methods: The in vitro pharmacokinetic characterization was performed for solubility, Caco-2 permeability, microsomal stability, CYP inhibition and plasma protein binding. In vivo pharmacokinetic studies were performed in Swiss albino mice, Sprague Dawley rats and Beagle dogs. The pharmacodynamic studies were carried out in mouse against S. pneumoniae in systemic infection and against S. pneumoniae and H. influenzae in rat lung infection models. Results: RBx14255 showed superior potency and efficacy in mouse and rat infection models. RBx14255 showed pH dependent solubility (0.41 mg/mL at pH 6.8 and >1 mg/mL at pH 1.2), moderate Caco-2 permeability (A to B: 12 nm/s) with high efflux ratio. It showed high plasma protein binding (>97%) in mouse and low binding (45-70%) in rat, dog and human. The compound is mainly metabolized through CYP3A4. Pharmacokinetic parameters and absolute bioavailability of both, RBx14255 and telithromycin are similar in mouse. Both the ketolides showed low plasma clearance (18% of the normal hepatic blood flow rate) in mouse, moderate to high clearance in rat and dog. Mean oral bioavailability was high in mouse (≥85%), moderate in rat (RBx14255: 15% and telithromycin: 51%) and high to moderate in dog (RBx14255: 98% and telithromycin: 56%). The predicted efficacious dose for a 70 kg man ranges from 124 mg BID to 226 mg BID. Conclusion: RBx14255 displayed significantly better pharmacodynamics which correlates with the pharmacokinetic properties against S. pneumoniae and H. influenzae as compared to telithromycin. The predicted human efficacious doses are in the range of 124-226 mg, making it amenable to oral dosage form drug in human. This could be a promising clinical candidate for future studies.

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SERUM CONCENTRATIONS OF PROTEIN REGULATORS OSTEOBLASTOGENESIS AND OSTEOCLASTOGENESIS IN PATIENTS WITH ENDOGENOUS HYPERCORTICISM

Osteoporosis and Bone Diseases ◽

10.14341/osteo201223-8 ◽

2012 ◽

Vol 15 (2) ◽

pp. 3-8

Author(s):

Zh E Belaya ◽

L Ya Rozhinskaya ◽

N V Dragunova ◽

A G Solodovnikov ◽

A V Ilyin ◽

...

Keyword(s):

Healthy Subjects ◽

Type I Collagen ◽

Control Group ◽

Type I ◽

Healthy Individuals ◽

Serum Samples ◽

Absolute Level ◽

Promising Therapeutic Approach ◽

Free Cortisol ◽

Healthy Control

Purpose. Endogenous Cushing’s syndrome (CS), usually affecting young and otherwise healthy patients, is a good model to validate the effects of supraphysiological levels of glucocorticoids in humans. This study evaluates circulating levels of extracellular antagonists of Wnt/ß-catenin signaling pathway (sclerostin, Dickkopf1 (Dkkl), secretedfrizzled-related protein 1 (SFRP1)) along with osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa-beta ligand (RANKL) in patients with CS as compared to healthy individuals. Materials and methods. Forty patients with clinically and biochemically evident CS and 40 sex, age and body-mass index matched healthy individuals provided fasting serum samples (8:00-10:00AM) for measurement of sclerostin, SFRP1 and Dkkl, RANKL., OPG along with bone turnover markers. Serum samples on RANKL., OPG., Dkkl, SFRP1, sclerostin were frozen and then concurrently measured by an enzyme immunoassay (ELISA) using commercially available reagents. Serum samples on osteocalcin (OC), carboxyterminal cross-linked telopeptide of type I collagen (CTx), cortisol in serum and saliva were assayed by electrochemiluminescence (ECLIA) Cobas e601 Roche. Urinary free cortisol (24hUFC) was measured by an immunochemiluminescence assay (extraction with diethyl ether) on a Vitros ECi. All participants were questioned regarding any recent low traumatic fractures. Patients with CS underwent standard spinal radiographs in anterior-posterior and lateral positions of the vertebrae Th4-L4 (Axiom Icons R200 "Siemens"). Results. Patents with CS (30 (26-40) years old with 24hUFC 2575 (1184-4228) nmol/l (Me (Q25-Q75)) had suppressed OC and normal CTx levels as compared to healthy subjects. A significant correlation, which we observed between OC and CTx (po=0.724 (p<0.001)) among the healthy volunteers, weakened to a non-significant level (po - 0.285 (p=0.083)) when analyzing patients with CS only. 24hUFC correlated with OC po = - 0.464 p=0.003, but not with CTx po= 0.245 (p=0.132) in patients with CS. Patients with CS had higher sclerostin levels versus healthy control subjects (p=0.032). Differences in sclerostin were due to the lack of lower sclerostin values rather than an increase in protein levels above the upper-limits of the healthy control individuals. Sclerostin levels higher than 662 pg/ml were four times more frequent in patients with CS as compared to healthy subjects (OR=4,19, 95% CI 1,44-12,22), p=0,006. Dkk1, SFRP1 did not differ from the control group. Patients with CS had a significantly lower level of RANKL (0.083 (0.075 0.093) pmol/L) as compared to healthy subjects (0.106 (0.089 0.131) pmol/L) p<0.001. Conversely, no difference was found between the OPG level in patients with CS (6.65 (4.92-7.66) pmol/L) and healthy individuals (5.77 (5.00-6.40) pmol/L), p=0.14. RANKL was lower (p=0.02) and OPG was higher (p=0.04) in patients with CS and low traumatic fractures (n=19) versus patients without fractures (n=21). Conclusions. Patients with CS have higher sclerostin level as compared to healthy subjects. Hypercotisolism prevents the normal physiological suppression of sclerostin rather than raising its absolute level. Of all the tested proteins (sclerostin, Dkk1, SFRP1, RANKL., OPG) only sclerostin seems to be a promising therapeutic approach to treating osteoporosis in patients with endogenous CS.

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