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.

• Klíčová slova
• Antiepileptic drugs, Biomechanical properties, Bone markers, Bone mineral density, Zonisamide,
• MeSH
• kosti a kostní tkáň * MeSH
• kostní denzita * MeSH
• krysa rodu Rattus MeSH
• orchiektomie MeSH
• potkani Wistar MeSH
• zonisamid farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• zinc sulfide MeSH Prohlížeč
• zonisamid MeSH

BACKGROUND: There are limited data on the effects of GBP on bone and no data for PGB. Some data suggest that there is a significant influence of sex hormone balance on the susceptibility of bone to antiepileptic drug-induced bone loss. METHODS: Forty-eight male Wistar rats were divided into six groups that were subjected to two surgeries, sham (noORX) or real orchidectomy (ORX), and were fed three diets, a SLD, a SLD enriched with GBP or a SLD enriched with PGB. Dual energy X-ray absorptiometry was used to measure the bone mineral density. The concentrations of bone turnover markers were assayed. The femurs were biomechanically tested. RESULTS: Significant reductions in bone mineral density, weight and biomechanical strength were observed in ORX animals. GBP or PGB exposure did not cause significant alterations in bone mineral density or biomechanical strength. No changes in bone turnover markers were observed, except for RANKL. A significant increase was found in the ORX GBP and ORX PGB groups. Within the orchidectomized animal group, RANKL levels were significantly higher in the ORX PGB group than in the ORX GBP group. CONCLUSIONS: Because neither GBP nor PGB affected bone mineral density or mechanical bone strength, both of these antiepileptic drugs could be considered drugs with lower risks to bone health. A shift in RANKL levels indicates that the effects of GBP and PGB on osteoclast activity may be dependent on the hormonal status of animals.

• Klíčová slova
• Amino-terminal propeptide of procollagen type I, Bone alkaline phosphatase, Bone mineral density, Receptor activator of nuclear factor-kappa B ligand,
• MeSH
• absorpční fotometrie metody   MeSH
• alkalická fosfatasa metabolismus   MeSH
• antikonvulziva farmakologie   MeSH
• biomechanika účinky léků   MeSH
• femur účinky léků   metabolismus   MeSH
• gabapentin farmakologie   MeSH
• kostní denzita účinky léků   MeSH
• krysa rodu Rattus MeSH
• orchiektomie metody   MeSH
• osteoprotegerin metabolismus   MeSH
• potkani Wistar MeSH
• pregabalin farmakologie   MeSH
• prospektivní studie MeSH
• remodelace kosti účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• antikonvulziva MeSH
• gabapentin MeSH
• osteoprotegerin MeSH
• pregabalin MeSH

Some data suggest that exposure to levetiracetam (LEV) might be associated with a risk for bone health in the model of orchidectomized rats. The aim of this study was to investigate if there is any significant risk of LEV for bone health in the model of gonadally intact animals. Wistar rats were divided into a control group and a test group, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed SLD enriched with LEV for 12 weeks. Dual energy X-ray absorptiometry was used to measure BMD of the whole body, femur and lumbar vertebrae. The concentrations of bone markers were examined in bone homogenate. Both femurs and tibiae were used for biomechanical testing. We found in the LEV group significantly decreased absolute and relative values of adipose tissue, higher whole-body BMD, higher right tibia cortical thickness, and a significantly increased concentration of Bone Alkaline Phosphatase (BALP) and cross-linked C-telopeptide of type I collagen (CTX-I) compared with the control group. The results suggest that the long-term administration of LEV in the model of gonadally intact rats does not have a negative effect on bone. Significant increase in BMD and cortical thickness of the right tibia may indicate even a positive influence on the properties of bone. Further studies will be necessary in animals and humans to confirm these findings.

• Klíčová slova
• Antiepileptic drugs, Biomechanical properties, Bone markers, Bone mineral density, Levetiracetam,
• MeSH
• bederní obratle anatomie a histologie   účinky léků   metabolismus   fyziologie   MeSH
• biologické markery metabolismus   MeSH
• biomechanika účinky léků   MeSH
• femur anatomie a histologie   účinky léků   metabolismus   fyziologie   MeSH
• kostní denzita účinky léků   MeSH
• krysa rodu Rattus MeSH
• levetiracetam MeSH
• piracetam analogy a deriváty   farmakologie   MeSH
• potkani Wistar MeSH
• tělesná hmotnost účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• levetiracetam MeSH
• piracetam MeSH

PURPOSE: Behavioral side effects of antiepileptic drugs (AEDs) are common including both positive and negative effects on mood, anxiety, depression, and psychosis. We aimed to evaluate behavioral patterns in rats after administration of lamotrigine, levetiracetam, phenytoin, topiramate, carbamazepine, gabapentin, pregabalin, and zonisamide. METHODS: The open-field test was performed and locomotion, rearing, grooming, central latency and defecation were recorded over a 5min interval for each rat (8 rats in each group receiving AED and 16 controls). Kruskal-Wallis nonparametric test or ANOVA were used to assess differences among the groups. RESULTS: The experimental groups did not differ in latency to enter the center compartment, neither in the decline of locomotor activity in the 1st and the 5th minute of the observation, nor in number of rears. Significant differences among groups were observed in the total number of lines crossed, grooming, as well in the number of fecal pellets. Locomotor activity was significantly increased in lamotrigine, if compared with gabapentin and pregabalin (ANOVA; p <0.05). Rats exposed to topiramate displayed a significantly increased number of grooming (when compared to pregabalin: p<0.01). Defecation (the number of fecal pellets) significantly increased in the gabapentin and carbamazepine group. CONCLUSION: There are significant differences between AEDs in terms of their behavioral profile. It is of great importance to evaluate these effects in clinical practice to bring more clear insight into these positive or negative side effects of AEDs.

• Klíčová slova
• Antiepileptic drugs, Anxiety, Behavior, Open-field test,
• MeSH
• afekt účinky léků   MeSH
• antikonvulziva krev   farmakologie   MeSH
• feces MeSH
• krysa rodu Rattus MeSH
• lokomoce účinky léků   MeSH
• neparametrická statistika MeSH
• pátrací chování účinky léků   MeSH
• péče o zevnějšek u zvířat účinky léků   MeSH
• potkani Wistar MeSH
• reakční čas účinky léků   MeSH
• tělesná hmotnost účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikonvulziva MeSH

OBJECTIVE: Some data suggest that exposure to lamotrigine (LTG) might be associated with impaired bone health in an orchidectomized rat model. The aim of this study was to determine if LTG poses any significant risk for bone in a gonadally intact animals and to compare the effect of LTG with that of phenytoin (PHT). METHOD: Twenty-four rats were divided into control and test groups, (n=8 per group). Control rats received a standard laboratory diet (SDL), while rats in the test groups were fed a SLD enriched with LTG or PHT for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). The concentrations of bone turnover markers (BTM) were assayed in bone homogenates. The femurs were measured and biomechanically tested. RESULTS: Treatment with either LTG or PHT had no significant effect on BMD or on the biomechanical strength of the bones. In contrast to the effect of LTG, we did find significant changes in BTM in the PHT group: a highly significant decrease in the osteoprotegerin/receptor activator of nuclear factor kappa B ratio (p<0.01) and highly significant increases in bone alkaline phosphatase and amino-terminal propeptide of procollagen type I (p<0.001, p˂0.01, respectively). In the LTG group, the only significant change was a decrease in sclerostin (p˂0.05). The PHT level was 19.0 (15.6-19.5) μmol/l, which represents the lower end of the therapeutic range used in humans. The level of LTG was 60.7 (58.5-61.8) μmol/l. CONCLUSIONS: LTG has no effect on the BMD, BTM or mechanical strength in gonadally intact animals. Although a low dose of PHT was associated with enhanced BTM, it did not affect BMD or the biomechanical properties of the bones, similar to the results observed for LTG.

• Klíčová slova
• Amino-terminal propeptide of procollagen type I, Bone alkaline phosphatase, Bone mineral density, Bone turnover markers, Osteoprotegerin/receptor activator of nuclear factor kappa B ratio, Sclerostin,
• MeSH
• absorpční fotometrie MeSH
• antikonvulziva farmakologie   MeSH
• biologické markery metabolismus   MeSH
• biomechanika MeSH
• fenytoin farmakologie   MeSH
• kosti a kostní tkáň diagnostické zobrazování   účinky léků   fyziologie   MeSH
• kostní denzita účinky léků   fyziologie   MeSH
• lamotrigin MeSH
• longitudinální studie MeSH
• potkani Wistar MeSH
• prospektivní studie MeSH
• remodelace kosti účinky léků   fyziologie   MeSH
• triaziny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antikonvulziva MeSH
• biologické markery MeSH
• fenytoin MeSH
• lamotrigin MeSH
• triaziny MeSH

OBJECTIVES: Acute myeloid leukemia (AML) cells are highly resistant to therapy. The presumed molecular basis of this resistance is the effect of tumor necrosis factor alpha (TNF-α) and other cytokines on endothelial adhesion molecule expression. The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules correlate in AML. METHODS: Baseline serum levels of 17 cytokines and 5 soluble adhesion molecules were measured in 53 AML patients using biochip array technology. Age, leukocyte count, secondary AML, CRP, FLT3-ITD and remission were variables. Statistical analysis was performed in R version 3.1.2. RESULTS: VCAM-1 correlated with ICAM-1 (P < 0.0001), E-selectin (P < 0.0001), leukocyte count (P = 0.0005) and TNF-α (P = 0.0035). E-selectin correlated with leukocyte count (P < 0.0001), P-selectin (P = 0.0032) and MCP-1 (P = 0.0119). CRP correlated with IL-6 (P < 0.0001), leukocyte count negatively correlated with IL-7 (P = 0.0318). FLT3-ITD was associated with higher E-selectin (P = 0.0010) and lower IL-7 (P = 0.0252). Secondary AML patients were older. Failure of induction therapy was associated with significantly higher CRP and lower P-selectin. Leukocyte count (P < 0.0001), FLT3-ITD (P = 0.0017) and secondary AML (P = 0.0439) influenced the principal component. CONCLUSIONS: Leukemic cells can modulate the microenvironment. Cytokine, adhesion molecule levels and leukocyte count correlate in AML. Understanding these mechanisms may form the basis of novel therapeutic approaches.

• Klíčová slova
• FLT3-ITD, TNF-alpha, acute myeloid leukemia, adhesion molecules, cytokines,
• MeSH
• akutní myeloidní leukemie krev   farmakoterapie   MeSH
• analýza hlavních komponent MeSH
• chemorezistence MeSH
• cytokiny metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekuly buněčné adheze metabolismus   MeSH
• počet leukocytů MeSH
• prospektivní studie MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• TNF-alfa fyziologie   MeSH
• tyrosinkinasa 3 podobná fms fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• FLT3 protein, human MeSH Prohlížeč
• molekuly buněčné adheze MeSH
• TNF-alfa MeSH
• tyrosinkinasa 3 podobná fms MeSH

BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) have become a widely accepted tool in the treatment of patients with symptomatic portal hypertension. The aim of our study was to assess glycogen phosphorylase BB (GPBB) concentration in relation to echocardiographic and haemodynamic parameters in patients before and after TIPS insertion. METHODS: The study population consisted of 55 patients (38 men and 17 women, age 55.6±8.9 years, range 37-74 years) with liver cirrhosis treated with transjugular portosystemic shunting. GPBB, echocardiographic, and haemodynamic parameters were measured before TIPS insertion and 24 h after the procedure. GPBB concentrations were assessed using the Cardiac Array for Evidence Investigator protein biochip. Correlation between parameters was assessed using the Spearman's coefficient. RESULTS: Serum post-procedural GPBB concentrations were increased in comparison with baseline (5.58 vs. 2.67 μg/L, P<0.001). GPBB concentration after TIPS significantly correlated with baseline systemic vascular resistence (r=0.330; P=0.017) and cardiac index (r=0.313; P=0.025). CONCLUSION: GPBB concentration measurement may be a useful tool for monitoring myocardial ischemia during a TIPS procedure.

• Klíčová slova
• TIPS, biochip, cardiac marker, cirrhosis, glycogen phosphorylase BB, portal hypertension,
• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• glykogenfosforylasa krev   MeSH
• hemodynamika fyziologie   MeSH
• jaterní cirhóza komplikace   enzymologie   patofyziologie   MeSH
• katetrizace centrálních vén MeSH
• lidé středního věku MeSH
• lidé MeSH
• portální hypertenze enzymologie   etiologie   chirurgie   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• transjugulární intrahepatální portosystémový zkrat * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• glycogen phosphorylase BB, human MeSH Prohlížeč
• glykogenfosforylasa MeSH

Our goal was to determine if venlafaxine has a negative effect on bone metabolism. Rats were divided into three groups. The sham-operated control group (SHAM), the control group after orchidectomy (ORX), and the experimental group after orchidectomy received venlafaxine (VEN ORX) in standard laboratory diet (SLD) for 12 weeks. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I (P1NP), bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 (BMP-2) were examined in bone homogenate. The femurs were used for biomechanical testing. Compared to the ORX group we found lower BMD in the diaphysis area of the femur in the VEN ORX group, suggesting a preferential effect on cortical bone. Of the bone metabolism markers, there was significant decrease (ORX control group versus VEN ORX experimental group) in BALP levels and increase in sclerostin and CTX-I levels, suggesting a decrease in osteoid synthesis and increased bone resorption. The results suggest that the prolonged use of venlafaxine may have a negative effect on bone metabolism. Further studies are warranted to establish whether venlafaxine may have a clinically significant adverse effect on bone.

• Klíčová slova
• BALP, Bone mineral density, CTX-I, SNRI, Venlafaxine,
• MeSH
• absorpční fotometrie MeSH
• alkalická fosfatasa metabolismus   MeSH
• bederní obratle diagnostické zobrazování   účinky léků   MeSH
• biologické markery metabolismus   MeSH
• biomechanika MeSH
• femur diagnostické zobrazování   účinky léků   MeSH
• genetické markery MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu toxicita   MeSH
• kolagen typu I metabolismus   MeSH
• kosti a kostní tkáň účinky léků   metabolismus   účinky záření   MeSH
• kostní denzita účinky léků   MeSH
• kostní morfogenetické proteiny metabolismus   MeSH
• kostní morfogenetický protein 2 metabolismus   MeSH
• lidé MeSH
• orchiektomie * MeSH
• osteoprotegerin metabolismus   MeSH
• peptidové fragmenty metabolismus   MeSH
• peptidy metabolismus   MeSH
• potkani Wistar MeSH
• prokolagen metabolismus   MeSH
• remodelace kosti účinky léků   MeSH
• tibie účinky léků   metabolismus   MeSH
• venlafaxin hydrochlorid toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• biologické markery MeSH
• Bmp2 protein, rat MeSH Prohlížeč
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• genetické markery MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu MeSH
• kolagen typu I MeSH
• kostní morfogenetické proteiny MeSH
• kostní morfogenetický protein 2 MeSH
• osteoprotegerin MeSH
• peptidové fragmenty MeSH
• peptidy MeSH
• procollagen Type I N-terminal peptide MeSH Prohlížeč
• prokolagen MeSH
• Sost protein, rat MeSH Prohlížeč
• Tnfrsf11b protein, rat MeSH Prohlížeč
• venlafaxin hydrochlorid MeSH

OBJECTIVE: Our study aimed to investigate the effect of mirtazapine on bone metabolism in the orchidectomized rat model. METHODS: Rats were divided into three groups. A sham-operated control group (SHAM group) and a control group after orchidectomy (ORX group) received the standard laboratory diet (SLD). An experimental group after orchidectomy (ORX MIRTA group) received SLD enriched with mirtazapine for 12 weeks. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone marker concentrations of osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I, bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 were examined in bone homogenate. The femurs were used for biomechanical testing. RESULTS: Compared with the control ORX group, we found a lower BMD in the ORX MIRTA group. The differences were statistically significant, although not in the lumbar vertebrae. BMD was lower in the MIRTA group, suggesting a preferential effect on cortical bone. However, although the thickness of the diaphyseal cortical bone was not different, the fragility in the femoral neck area was statistically significantly different between the groups in biomechanical testing. Regarding the bone metabolism markers, there was a significant decrease in OPG and BALP levels, suggesting a reduction in osteoid synthesis. CONCLUSIONS: The results suggest that prolonged use of mirtazapine may have a negative effect on the synthesis of bone and on its mechanical strength, especially in the femoral neck. Further studies are warranted to establish whether mirtazapine may have a clinically significant adverse effect on bone exclusively in the model of gonadectomized rats, or whether the effect occurs also in the model of gonadally intact animals and in respective human models.

• MeSH
• alfa blokátory krev   farmakokinetika   farmakologie   MeSH
• alkalická fosfatasa metabolismus   MeSH
• antidepresiva tricyklická krev   farmakokinetika   farmakologie   MeSH
• biomechanika MeSH
• kosti a kostní tkáň účinky léků   metabolismus   fyziologie   MeSH
• kostní denzita účinky léků   MeSH
• mianserin analogy a deriváty   krev   farmakokinetika   farmakologie   MeSH
• mirtazapin MeSH
• orchiektomie MeSH
• osteoprotegerin metabolismus   MeSH
• pevnost v tlaku MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa blokátory MeSH
• alkalická fosfatasa MeSH
• antidepresiva tricyklická MeSH
• mianserin MeSH
• mirtazapin MeSH
• osteoprotegerin MeSH
• Tnfrsf11b protein, rat MeSH Prohlížeč