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Open access

Rafał Mazur, Sebastian Masternak, Michał Pająk, Nikodem Skoczeń, Ewelina Soroka and Marcin Olajossy

Abstract

Introduction: Smoking is a huge medical and social problem in Poland, with as many as about 24% of Poles being addicted to nicotine. Approximately 6 million people worldwide die every year from conditions that are closely related to tobacco addiction, such as cancer and cardiovascular, metabolic or lung diseases. The difficulty in combatting nicotine dependence is largely due to the complex mechanism of this addiction. The motivation of a patient to quit smoking is of great importance in the difficult withdrawal process. Strengthening this motivation is one of the most important tasks of physicians and addiction therapists.

Overview of literature: Nicotine replacement therapy (NRT) has been the most widely known way to break away from smoking addiction for many years now. It involves delivering nicotine to the body in ways that are less harmful than through tobacco smoke. As a consequence, the cravings for nicotine are reduced, making it easier for the patient to break with the addiction. Clinical trials have shown that the use of NRT is associated with a 50-70% increased chance of maintaining abstinence from smoking compared to placebo. There are many NRT products, including nicotine chewing gum, nicotine patches, lozenges, dissolvable nicotine sticks, or inhalers. Bupropion is a selective dopamine–noradrenaline reuptake inhibitor. This drug is one of the most commonly used in the pharmacotherapy of depression in the United States. At the same time, it has been found to have a positive effect on people trying to break up with the habit of smoking cigarettes. The mechanism of action remains unknown in this case, but studies clearly indicate the efficacy of bupropion, which is comparable to the efficacy of NRT. Varenicline is a partial agonist selective for α4β2 nicotinic acetylcholine receptors. It has a higher affinity for these receptors than nicotine. By stimulating them, it causes an increase in dopamine secretion (but to a lesser extent than cigarette smoking), helping in this way ease withdrawal symptoms.

Conclusions: Varenicline has higher efficacy than bupropion and NRTs. Simultaneous use of two NRT forms increases the effectiveness of this method to a level comparable to varenicline. Contrary to previous reports, it seems that varenicline does not increase self-aggressive behaviour and the risk of suicide. The effectiveness of antinicotinic drugs depends on the sex of the patient. For both sexes, the most effective drug is varenicline. It is slightly more effective in women than in men. By contrast, NRT and bupropion show greater therapeutic potential in men.

Open access

Sara Tomczak, Hanna Gorejko and Wiktor Dróżdż

Abstract

Introduction: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease with undetermined etiology. Due to diverse symptomatology, it requires a thorough differential diagnosis, with consideration of conversion disorders. The presented thesis describes a case of a young man hospitalized in the Department of Psychiatry in order to verify the possible psychogenic basis of his symptoms, which previously were considered to be a manifestation of neurological disease with an unfavorable prognosis.

Aim: The aim of the thesis is to raise the issue of a multidisciplinary approach to diagnostic process in medicine, as well as taking into account the legitimacy of including psychiatrists, psychologists, and psychotherapists in diagnostic teams.

Case study: We present a case report of a man who has been experiencing progressive feeling and walking problems for the past several years, which originally suggested a neurological or rheumatological disease. Earlier observations and medical tests had led to a diagnosis of amyotrophic lateral sclerosis. After several years, the diagnosis was excluded, and the patient was referred to the Department of Psychiatry to determine the possible psychogenic basis of his symptoms. Diagnostic methods used during the patient’s hospitalization confirmed the conversational nature of his symptoms, and both pharmacological and psychotherapeutic treatment caused reduction of severity of his symptoms and allowed him for a gradual return to independent functioning.

Conclusion: Analysis of the collected data, including patient’s life history and a course of his treatment, indicates the validity of a holistic approach to medical problems, which implies the inclusion of specialists in the field of psychiatry, psychology, as well as psychotherapists in diagnostic teams. Such a multidimensional view of the patient and the source of his symptoms may allow for faster diagnosis and may also contribute to reducing the risk of making mistakes such as an incorrect assessment of factors triggering the disease process.

Open access

Terezia Valkovicova, Martina Skopkova, Juraj Stanik and Daniela Gasperikova

Abstract

MODY (Maturity Onset Diabetes of the Young) is a type of diabetes resulting from a pathogenic effect of gene mutations. Up to date, 13 MODY genes are known. Gene HNF1A is one of the most common causes of MODY diabetes (HNF1A-MODY; MODY3). This gene is polymorphic and more than 1200 pathogenic and non-pathogenic HNF1A variants were described in its UTRs, exons and introns. For HNF1A-MODY, not just gene but also phenotype heterogeneity is typical. Although there are some clinical instructions, HNF1A-MODY patients often do not meet every diagnostic criteria or they are still misdiagnosed as type 1 and type 2 diabetics. There is a constant effort to find suitable biomarkers to help with in distinguishing of MODY3 from Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). DNA sequencing is still necessary for unambiguous confirmation of clinical suspicion of MODY. NGS (Next Generation Sequencing) methods brought discoveries of multiple new gene variants and new instructions for their pathogenicity classification were required. The most actual problem is classification of variants with uncertain significance (VUS) which is a stumbling-block for clinical interpretation. Since MODY is a hereditary disease, DNA analysis of family members is helpful or even crucial. This review is updated summary about HNF1A-MODY genetics, pathophysiology, clinics functional studies and variant classification.

Open access

Dmytro O. Minchenko

Abstract

Objective. The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes through changes in the expression of numerous regulatory genes.

Methods. The expression level of HLA-DRA, HLA-DRB1, HLA-G, HLA-F, and NFX1 genes as well as miR-190b was measured in the blood of obese adolescents without signs of resistance to insulin and with insulin resistance in comparison with the group of relative healthy control individuals without signs of obesity.

Results. It was shown that obesity without signs of insulin resistance is associated with upregulation of the expression level of HLA-DRA and HLA-DRB1 genes, but with down-regulation of HLA-G gene expression in the blood as compared to control group of relative healthy adolescents. At the same time, no significant changes were observed in the expression level of HLA-F and NFX1 genes in the blood of this group of obese adolescents. Development of insulin resistance in obese individuals leads to significant down-regulation of HLA-DRA, HLA-DRB1, HLA-G, and HLA-F gene expressions as well as to up-regulation of NFX1 gene as well as microRNA miR-190b in the blood as compared to obese patients without signs of insulin resistance.

Conclusions. Results of this study provide evidence that obesity affects the expression of the subset of genes related to immune response in the blood and that development of insulin resistance in obese adolescents is associated with strong down-regulation of the expressions of HLA-DRA, HLA-DRB1, HLA-F, and HLA-G genes, which may be contribute to the development of obesity complications. It is possible that transcription factor NFX1 and miR-190b participate in downregulation of HLA-DRA gene expression in the blood of obese adolescents with insulin resistance.

Open access

Shokoufeh Taherkhani, Fatemeh Moradi, Masoumeh Hosseini, Mohsen Alipour and Hadi Feizi

Abstract

Objective. Ghrelin, a 28 amino acid peptide, has diverse physiological roles. Phosphatidylino-sitol-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) are involved in some of the recognized actions of ghrelin. It has been shown that ghrelin upregulates HOXB4 gene expression but the real mechanism of this effect is not clear.

Methods. Rat bone marrow stromal cells (BMSCs) were cultured in DMEM. BMSCs were treated with ghrelin (100 μM) for 48 h. Real-time PCR for HOXB4 was performed from Control (untreated BMSCs), BG (BMSCs treated with 100 µM ghrelin), PD (BMSCs treated with 10 µM PD98059, a potent inhibitor of mitogen-activated protein kinase, and 100 µM ghrelin), LY (BM-SCs treated with 10 µM LY294002, a strong inhibitor of phosphoinositide 3-kinase, and 100 µM ghrelin) and SY (BMSCs treated with 10 µM LY294002 plus 10 µM PD98059, and 100 µM ghrelin) groups. Relative gene expression changes were determined using Relative expression software tool 9 (REST 9).

Results. HOXB4 gene has been overexpressed in ghrelin-treated BMSCs (p<0.05). PI3K inhi-bition by LY294002 significantly downregulated the ghrelin-induced overexpression of HOXB4 (p<0.05).

Conclusion. We can conclude that ghrelin, through PI3K/Akt pathway, may improve BMSC transplantation potency by reducing its apoptosis. Moreover, upregulating HOXB4 in BMSC and its possible differentiation to HSCs might in the future open the doors to new treatment for hematologic disorders. Therefore, activating the PI3K/Akt pathway, instead of using a non-specific inducer, could be the principal point to increase the efficiency of BMSC-based cell therapies in the future.

Open access

Alexandra Padova, Ivana Rokytova, Boris Mravec, Richard Kvetnansky and Peter Vargovic

Abstract

Objectives. Despite extensive research efforts, mechanisms participating on development of Alzheimer’s disease (AD) are covered only partially. Data from the last decades indicate that various stressors, as etiological factors, may play a role of in the AD. Therefore, we investigated the effect of two acute stressors, immobilization (IMO) and lipopolysaccharide (LPS), on the AD-related neuropathology.

Methods. Adult C57BL/6J mice males were exposed to a single IMO stress or a single intraperitoneal injection of LPS (250 µg/kg body weight). After terminating the experiments, the brains were removed and their cortices isolated. Gene expression of pro-inflammatory cytokines, as well as expression of genes implicated in the AD neuropathology were determined. In addition, mediators related to the activation of the microglia, monocytes, and perivascular macrophages were determined in brain cortices, as well.

Results. In comparison with the control animals, we found increased gene expression of proinflammatory mediators in mice brain cortex in both IMO and LPS groups. In stressed animals, we also showed an increased expression of genes related to the AD neuropathology, as well as positive correlations between genes implicated in AD development and associated neuroinflammation.

Conclusions. Our data indicate that acute exposure to a strong IMO stressor, composed of the combined physical and psychological challenges, induces similar inflammatory and other ADrelated neuropathological changes as the immune LPS treatment. Our data also indicate that cytokines are most likely released from the peripheral immune cells, as we detected myeloid cells activity, without any microglia response. We hypothesize that stress induces innate immune response in the brain that consequently potentiate the expression of genes implicated in the AD-related neuropathology.

Open access

Ana B. Segarra, Isabel Prieto, Magdalena Martinez-Canamero, Jose-Ignacio Ruiz-Sanz, M. Begona Ruiz-Larrea, Marc De Gasparo, Inmaculada Banegas, Stefan Zorad and Manuel Ramirez-Sanchez

Abstract

Objective. Enkephalins are neuropeptides involved in functions such as pain modulation and/ or cognitive processes. It has been reported that dietary fat modifies enkephalins in the brain. Since enkephalins are hydrolyzed by enkephalinases, the study of the influence of dietary fats, differing in their degree of saturation, on brain fatty acids content and enkephalinase activity is important to understand its regulatory role on neuropeptides under different type of diets.

Methods. We analyzed enkephalinase activity, assayed with alanine-β-naphthylamide as sub-strate, in frontal cortex of adult male rats fed diets supplemented with fish oil, olive oil or coconut oil, which markedly differed in the saturation of their fatty acids.

Results. Rats fed a diet enriched with coconut oil had lower soluble enkephalinase activity than the group fed olive oil (p<0.01) and fish oil (p<0.05) whereas rats fed a diet enriched with fish oil had lower membrane-bound enkephalinase activity than the group fed with olive (p<0.001) or coconut oil (p<0.05). Significant negative correlations were observed between certain fatty acids and enkephalinase activities in the groups fed with olive and coconut oils. No correlations were observed in the group fed with fish oil.

Conclusions. Dietary fat modifies enkephalinase activity in the frontal cortex depending on the degree of saturation of the used oil. It is postulated that the functions, in which enkephalins are involved, such as pain modulation or cognitive functions, may also be affected according to the type of oil used in the diet.

Open access

Nasim Malekmohamadi, Alireza Abdanipour, Mehrdad Ghorbanlou, Saeed Shokri, Reza Shirazi, Eva Dimitriadis and Reza Nejatbakhsh

Abstract

Objective. Stem cell therapy, specifically, pre-induction of mesenchymal stem cells toward male germ-like cells may be useful in patients with azoospermia. The aim of this study was to evaluate in vitro differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) into male germ-like cells by indirect co-culture with testicular cells in the presence of bone morphogenetic protein 4 (BMP4).

Methods. Experimental groups included: control (mouse BMSCs), treatment group-1 (BMSCs treated with BMP4), treatment group-2 (indirect co-culture of BMSCs with mouse testicular cells in the presence of BMP4) and treatment group-3 (indirect co-culture of BMSCs with testicular cells). BMSCs-derived male germ-like cells were evaluated by the expression of Dazl, and Stra8 using RT-qPCR.

Results. Stra8 gene expression was significantly increased in the treatment group-2 and Dazl gene was significantly increased in the treatment group-1 compared to other groups. In conclusion, indirect co-culturing of BMSCs with testicular cells and BMP4 leads to the differentiation of BMSCs into male germ-like cells which express specific male germ-like genes. Testicular cells released factors that contributed to the differentiation of BMSCs into male germ progenitor cells.

Conclusion. This study suggests that mesenchymal stem cells may be differentiated into male germ-like cells and therefore, may be a novel treatment option for men with azoospermia.

Open access

Jana Osacka, Lubica Horvathova, Alena Cernackova and Alexander Kiss

Abstract

Objective. Prolonged treatment with neuroleptics has been shown to induce FosB/ΔFosB expression in several brain regions including the medial prefrontal cortex, dorsomedial and dorsolateral striatum, ventrolateral and dorsolateral septum, nucleus accumbens shell and core, and the hypothalamic paraventricular nucleus (PVN). Some of these regions are known to be also stress responsive. This study was designed to determine whether repeated clozapine (CLZ) administration for 7 consecutive days to Wistar rats may modify FosB/ΔFosB expression in the above-mentioned brain areas induced by acute stress or novel stressor that followed 13-day chronic mild stress preconditioning.

Methods. Following experimental groups were used: unstressed animals treated with vehicle/ CLZ for 7 days; 7-day vehicle/CLZ-treated animals on the last day exposed to acute stress – forced swimming (FSW); and animals preconditioned with stress for 13 days treated from the 8th day with vehicle/CLZ and on the 14th day exposed to novel stress – FSW.

Results. In the unstressed animals CLZ markedly increased FosB/ΔFosB immunoreactivity in the ventrolateral septum and PVN. FSW elevated FosB/ΔFosB expression in the medial prefrontal cortex, striatum, and septum. CLZ markedly potentiated the effect of the FSW on FosB/ΔFosB expression in the PVN, but suppressed it in the dorsomedial striatum. Novel stress with stress preconditioning increased FosB/ΔFosB immunoreactivity in the prefrontal cortex, striatum, ventrolateral septum, and the PVN. In the nucleus accumbens the effect of the novel stressor was potentiated by CLZ.

Conclusion. Our data indicate that CLZ may modulate the acute as well as novel stress effects on FosB/ΔFosB expression but its effect differs within the individual brain regions.

Open access

Nazli Khajehnasiri, Homayoun Khazali, Farzam Sheikhzadeh and Mahnaz Ghowsi

Abstract

Objective. The hypothalamic arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) circuitries are involved in the inhibition and stimulation of the appetite, respectively. The aim of this study was to investigate the effects of one-month lasting high-intensity exercise on the POMC mRNA and NPY mRNA expression in the above-mentioned brain structure and appetite and food intake levels.

Methods. Fourteen male Wistar rats (250±50 g) were used and kept in the well-controlled conditions (22±2 °C, 50±5% humidity, and 12 h dark/light cycle) with food and water ad libitum. The rats were divided into two groups (n=7): 1) control group (C, these rats served as controls) and 2) exercised group (RIE, these rats performed a high-intensity exercise for one month (5 days per week) 40 min daily with speed 35 m/min. The total exercise time was 60 min. The body weight and food intake were recorded continuously during the experiments.

Results. The results showed relative mRNA expression of POMC and NPY estimated in the hypothalamic arcuate nucleus. There were no significant differences in the NPY and POMC mRNAs expression levels and food intake between C and RIE groups.

Conclusions. The present data indicate that one-month regular intensive exercise did not alter the levels of NPY and POMC mRNAs expression (as two important factors in the regulation of appetite) in the hypothalamic arcuate nucleus and food intake suggesting that this type of exercise itself is not an appropriate procedure for the body weight reduction.