Hana Kuzelova

Publications (9)14.21 Total impact

• Article: Co-morbidity and self medication in schizophrenia: involvement of endogenous morphine signaling mechanisms.

  Richard M Kream, Hana Kuzelova, Milena Kralickova, Radek Ptacek, George B Stefano
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  ABSTRACT: For over 30 years, empirical studies have demonstrated expression of chemically authentic morphine by diverse animal tissues and organs systems. De novo biosynthesis of endogenous morphine by animal cells displays striking similarities to the multi-enzyme mediated biosynthetic pathway previously characterized in great biochemical and molecular detail in opium poppy (Papaver somniferum). The committed enzyme step within this pathway involves an asymmetric Pictet-Spengler condensation of dopamine (DA) and 3,4 dihydroxyphenylacetaldehyde (DOPAL), the oxidation product of L- 3,4-dihydroxyphenylalanine (L-DOPA), to form the essential intermediate precursor tetrahydropapaveroline (THP). We have hypothesized that endogenous morphine is synthesized within peripheral sites via conversion of THP in a regulated biosynthetic pathway, or conversely, THP may be directly transported into the CNS and converted to endogenous morphine within a similar biosynthetic pathway. The fundamental chemical relationship of the prototype catecholamine DA and its immediate precursor L-DOPA to endogenous morphine expression indicates a novel reciprocally interactive mechanism that links catecholamine and "morphinergic" pathways in the activation and inhibition of key physiological responses, including higher order neural integration. Dysregulation of interactive DAergic and "morphinergic" signaling pathways within CNS foci may contribute to the etiological factors driving co-morbid behavioral syndromes in major psychiatric disorders. Our short review is designed to provide insights on comorbidity and self-medication in schizophrenia from a novel perspective involving endogenous morphine signaling mechanisms.
  Current drug targets 08/2012; 13(11):1454-7. · 3.93 Impact Factor
• Article: Parkinson's disease, L-DOPA, and endogenous morphine: a revisit.

  George B Stefano, Kirk J Mantione, Milena Králíčková, Radek Ptacek, Hana Kuzelova, Tobias Esch, Richard M Kream
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  ABSTRACT: Clinical observations stemming from widespread employment of restorative L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in Parkinson's Disease (PD) patients implicate a regulatory role for endogenous morphine in central nervous system dopamine neurotransmission. Reciprocally, it appears that restorative L-DOPA administration has provided us with a compelling in vivo pharmacological model for targeting peripheral sites involved in endogenous morphine expression in human subjects. The biological activities underlying endogenous morphine expression and its interaction with its major precursor dopamine strongly suggest that endogenous morphine systems are reciprocally dysregulated in PD. These critical issues are examined from historical and current perspectives within our short review.
  Medical science monitor: international medical journal of experimental and clinical research 08/2012; 18(8):RA133-137. · 1.70 Impact Factor
• Article: Low dose morphine adjuvant therapy for enhanced efficacy of antipsychotic drug action: potential involvement of endogenous morphine in the pathophysiology of schizophrenia.

  George B Stefano, Milena Králíčková, Radek Ptacek, Hana Kuzelova, Tobias Esch, Richard M Kream
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  ABSTRACT: Major thematic threads linking extensive preclinical and clinical efforts have established a working mechanistic scheme whereby atypical antipsychotic drugs ameliorate negative DSM IV diagnostic criteria by effecting relatively potent blockade of serotonin (5-HT)(2A) receptors coupled with weaker antagonism of dopamine D(2) receptors in frontal cortical areas. These contentions are more or less supported by in vitro binding experiments employing cloned receptors on cultured cells, although significant functional involvement of 5-HT(2C) receptors has also been proposed. It is interesting that a key statistical analysis indicates a major shift in usage back to typical antipsychotic agents for management of schizophrenia from 1995-2008, whereas off-label usage of atypical antipsychotic agents was markedly increased or expanded for bipolar affective disorder. Importantly, meta-analyses generally did not support efficacy differences between the other atypical antipsychotics compared with the older typical agents. A critical examination of putative functional linkages of morphine and its type-selective mu opioid receptor to higher order cortical regulation of cognitive processes may provide novel insights into human behavioral processes that are severely impaired in schizophrenia spectrum disorders.
  Medical science monitor: international medical journal of experimental and clinical research 06/2012; 18(7):HY23-6. · 1.70 Impact Factor
• Article: Genetics in Psychiatry - up-to-date review 2011.

  Radek Ptacek, Hana Kuzelova, George B Stefano
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  ABSTRACT: Psychiatric genetics is a popular and much-discussed topic. Many candidate genes have been investigated in relation to psychiatric disorders and many connections have been found. The utilization of these investigations is currently at a theoretical level. Nevertheless, these findings of candidate genes will be important for further research and subsequent clinical use, for example in pharmacogenetics). Due to the rapidly growing number of empirical studies that provide profound analysis of different genes and their variants in different psychiatrical symptomatology, the field is highly divided, and providing a succinct overview is challenging. This article attempts to provide an up-to-date review of the most important and most discussed genes (mainly transporter and receptor genes) contributing to the etiology of psychiatric disorders.
  Neuro endocrinology letters 08/2011; 32(4):389-99. · 1.30 Impact Factor
• Article: Circadian rhythms of saliva melatonin in ADHD, anxious and normal children.

  Ivo Paclt, Radek Ptácek, Hana Kuzelová, Nikol Cermáková, Alexandra Trefilová, Patricie Kollárová, Tereza Cálková, Ladislav Csemy, Libor Cíhal
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  ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders are the most frequent psychiatric disorders in children. Changes in rhythms of symptoms during the day may be influenced by genetic, biological and psychological factors. Some changes of melatonin rhythm may hypothetically change the activity of ADHD by changing arousal or in anxiety children by changing their emotional state. In our present study we identify one group of ADHD children combine type without comorbids, one group of anxiety children and a control group. Most changes of melatonin daily rhythm are supposed in the anxiety group, especially in sleeping time, and more prominent change in the ADHD group with prominent hyperactivity and conduct disorder symptoms. Thirty-four ADHD and forty-three control children and eleven anxiety children, all 6-12 years old, participated in the study. The saliva specimens were collected in four different sessions during the school year, around the time of the spring and autumn equinox, when the natural light lasted 11.2 h ± 0.9 h. In our study more symptoms of conduct disorder elevated positive or negative correlations between psychopathology and saliva level of melatonin in ADHD and anxiety samples. We hypothesize that co-morbidity of ADHD or anxiety with impulsivity and conduct disorders might have elevated correlations between psychopathology of ADHD or anxiety and plasma melatonin level.
  Neuro endocrinology letters 01/2011; 32(6):790-8. · 1.30 Impact Factor
• Article: The serotonin transporter gene (5-HTT) variant and psychiatric disorders: review of current literature.

  Hana Kuzelova, Radek Ptacek, Milan Macek
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  ABSTRACT: Both serotonin and the serotonin transporter, which transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons, play an important role in the pathophysiology of several psychiatric disorders. Mutations associated with the serotonin transporter gene may result in changes in serotonin transporter function. The serotonin transporter gene promoter variant, consisting of a long (L) and a short (S) variant, is one of the major factors which contribute to the etiology of many psychiatric disorders. In this regard, many studies have been published on association of this variant with various psychiatric disorders. This repeat length variant in the promoter region of this gene has been shown to affect the rate of serotonin uptake and may play a role in post-traumatic stress disorder and depression-susceptibility in people experiencing emotional trauma. Associations between a functional variant in the serotonin transporter anxiety-related personality traits were found, as well as the risk of developing depression, alcoholism or suicidal behavior. Understanding of possible associations of these variants and psychiatric disorders would bring progress in principles and treatment of many disorders.
  Neuro endocrinology letters 02/2010; 31(1):4-10. · 1.30 Impact Factor
• Article: ADHD and growth: anthropometric changes in medicated and non-medicated ADHD boys.

  Radek Ptacek, Hana Kuzelova, Ivo Paclt, Ilja Zukov, Slavomil Fischer
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  ABSTRACT: ADHD children can show changes in growth and development. Many studies describe these changes as a side effect of stimulant medication. However, changes in somatic development can also appear in non-medicated children. This suggests that the changes could be a manifestation of the disorder itself and not just a side effect of the treatment. This study compared anthropometric characteristics in medicated and non-medicated ADHD boys (n=104, age 4-16 years) with the normal non-clinical population. In contrast to most previous studies, complex anthropometrical measurements were used. The results showed significant differences between children with ADHD and those without the diagnosis, the differences found to be statistically significant (p<0.01) being signs of nutrition (percentage of fat, abdominal circumference) and growth suppression (lower body height, smaller head circumference). Differences between the medicated and non-medicated groups corresponded only to a lower value of body fat in the medicated children. These results suggest that growth changes in ADHD children may be more specific to the disorder itself than to stimulant treatment.
  Medical science monitor: international medical journal of experimental and clinical research 12/2009; 15(12):CR595-9. · 1.70 Impact Factor
• Article: Anthropometric changes in non-medicated ADHD boys.

  Radek Ptacek, Hana Kuzelova, Ivo Paclt, Ilja Zukov, Slavomir Fischer
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  ABSTRACT: The aim of the study is to compare complex anthropometric characteristics in non medicated boys with ADHD and normal population. Complex anthropometric examination of non-medicated ADHD boys (n=46, average age 11.03 years), statistical and clinical comparison to the actual population growth norm. In contrast to the most of the previous studies, which analyzed mostly only BMI or basic signs of growth as height and weight, the presented study operates with a complex anthropometrical measurement and comparison with actual population norm. The results of the study show significant differences in the signs of nutrition (percentage of fat) and growth indicators (lower values of height) between ADHD and non ADHD children. Further anthropometrical parameters show other possible but in the studied sample statistically non-significant differences. Many studies analyzed growth relation to medication of ADHD children, but did not consider that the changes could appear also in non-medicated children and thus they might not be only a side effect of the treatment but a manifestation of the disorder itself. Growth changes in non-medicated children are not described well enough, so the presented study was performed to compare anthropometrics characteristics in ADHD boys with norm of nonclinical population and specify the differences. The results points to hypothesis that the growth changes are primarily caused by the disorder itself.
  Neuro endocrinology letters 08/2009; 30(3):377-81. · 1.30 Impact Factor
• Source

  Available from: activitas.org

  Article: Effect of stimulants on growth of ADHD children: A critical review

  Radek Ptacek, Hana Kuzelova, Ivo Paclt
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  ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed childhood psychiatric disorders manifested in almost every part of children's behavior. The most common treatment of ADHD is medication with stimu-lants, by specific amphetamine and methylphenidate. It is known that the treatment by stimulants may be accompanied by side effects from among decrease of appetite or changes in development as growth suppression and loss of weight which may present very serious phenomenon. Although many studies have monitored changes in growth and weight dur-ing medication, they did not provide definite results that the growth and weight suppression are caused by medication or not. According to many studies the height deficit is approximately amounted to 1 cm/year during the first 3 years of the treatment and can be clinically serious. Contrary to these findings some authors reported that the growth or weight changes can be a natural symptom of ADHD and not just a consequence of medication. The present article reviews key studies monitoring changes in parameters of growth in medicated children with ADHD, compares their results and sug-gest methodology improvements for further studies.
  Activitas nervosa superior 01/2009; 514:140-146.