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1.
Am J Case Rep ; 24: e941975, 2023 Dec 20.
Article En | MEDLINE | ID: mdl-38115572

BACKGROUND Eyelid tumors belong to a diverse group of neoplasms ranging from benign lesions to malignant tumors. Poromas are common, benign, mostly unpigmented tumors of the epidermal sweat duct unit, that usually grow slowly and occur in elderly people on the palms and soles. In most poroma cases some gene fusions were detected, which were caused by chromosomal aberrations. CASE REPORT We report the atypical case of a 30-year-old female patient suffering for more than 15 years from a solitary, polypoid, pigmented formation with a focal tuberous surface on the left lower eyelid. The lesion was not growing during the first years, but in the last 6 months before diagnosis its size more than doubled, finally reaching 12×14 mm. It was removed and histopathological analysis confirmed the diagnosis of a rare tumor - a poroma. There were no complications during healing and no recurrence was reported. CONCLUSIONS There have so far been only 9 reports of eyelid poromas, and the presented case significantly differed from the previous ones, as it appeared at an early age and showed rapid growth during a short time due to the war-related acute psychological stress. Moreover, it had unusual pigmentation and unpleasant smell. Reporting such untypical cases is clinically important because it is crucial to be aware of the diversity of eccrine poroma manifestation to distinguish it from malignant lesions.


Pigmentation Disorders , Poroma , Sweat Gland Neoplasms , Adult , Female , Humans , Diagnosis, Differential , Eyelids , Poroma/diagnosis , Poroma/pathology , Sweat Gland Neoplasms/diagnosis , Sweat Gland Neoplasms/surgery , Sweat Gland Neoplasms/pathology
2.
Front Oncol ; 13: 1265479, 2023.
Article En | MEDLINE | ID: mdl-37965467

We report the case of a patient who was diagnosed with two melanomas and one skin cancer within two years. Of particular interest was the fact, that at the time these tumors were diagnosed, the patient was already suffering from chronic myeloid leukemia, which developed three months after recovering from Covid-19. From the time of leukemia occurrence, the patient has been taking the tyrosine kinase inhibitor (TKI) - Gleevec. Thus, we took into the account the possibile effect of Gleevec administration on the risk of skin tumor appearance. It was also important to analyze the impact of the SARS-CoV-2 virus and chronic myeloid leukemia on the risk of secondary malignancies. According to so far published data, the direct relationship between Gleevec treatment and the occurrence of skin cancers cannot be proved. However, literature data indicate a direct and indirect relationship between SARS-CoV-2 infection and an increased incidence of carcinogenesis.

3.
Med Sci Monit ; 29: e939452, 2023 Mar 25.
Article En | MEDLINE | ID: mdl-36964642

BACKGROUND The increasing number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections has opened a new research direction related to analyzing long-term immune response and accurately characterizing individual cases of reinfection to understand its mechanism and estimate the risk of widespread reinfection both locally and globally. This retrospective study from the Gyncentrum Genetic Laboratory in Sosnowiec, Poland aimed to evaluate reinfections from SARS-CoV-2 between April 2020 and July 2022. MATERIAL AND METHODS The study extended the previously published report on SARS-CoV-2 infection cases in Poland by analyzing 8041 reinfections diagnosed with real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Data were collected on the amount of time elapsed from the first infection to the next and, based on these data, all results were divided into several groups for statistical analysis: 0-44, 45-90, 91-200, 201-310, 311-420, and >420 (days). RESULTS The study showed that of the 8041 patients who experienced reinfection, the vast majority (5505) became reinfected more than 310 days after the original infection, even though the average time between infections was 354.3 days. Statistical analysis revealed that the risk of SARS-CoV-2 reinfection increases with time and that this relationship becomes statistically significant after the 200th day following the initial infection (p<0.01). CONCLUSIONS We have shown that acquired immunity to SARS-CoV-2 infection is relatively short-lived - it starts diminishing about 6 months after the initial positive test. Moreover, the risk of reinfection is very high more than 1 year after the initial infection.


COVID-19 , SARS-CoV-2 , Humans , Retrospective Studies , Poland/epidemiology , Reinfection
4.
J Biomed Mater Res B Appl Biomater ; 110(3): 547-563, 2022 03.
Article En | MEDLINE | ID: mdl-34478207

The nonviable allogeneic human skin grafts might be considered as the most suitable skin substitutes in the treatment of extensive and deep burns. However, in accordance to biological security such grafts require the final sterilization prior to clinical application. The aim of the study was to verify the influence of electron beam irradiation of three selected doses: 18, 25, and 35 kGy on the extracellular matrix of human skin. Prior to sterilization, the microbiological tests were conducted and revealed contamination in all examined cases. Individual groups were subjected to single electron beam radiation sterilization at proposed doses and then subjected to microbiological tests again. The results of microbiological testing performed for all irradiation doses used were negative. Only in the control group was a growth of microorganisms observed. The FTIR spectrometry tests were conducted followed by the histological evaluation and mechanical tests. In addition, cost analysis of radiation sterilization of individual doses was performed. The results of spectroscopic analysis, mechanical tests, and histological staining showed no significant changes in composition and characteristics of tested tissues after their irradiation, in comparison to control samples. The cost analysis has shown that irradiation with 18 kGy is the most cost-effective and 35 kGy is the least favorable. However, according to biological risk reduction, the recommended sterilization dose is 35 kGy, despite the higher price compared to the other doses tested.


Electrons , Hematopoietic Stem Cell Transplantation , Extracellular Matrix , Gamma Rays , Humans , Skin Transplantation , Sterilization/methods
5.
Nutr Neurosci ; 24(11): 896-906, 2021 Nov.
Article En | MEDLINE | ID: mdl-31736434

OBJECTIVES: It is hypothesized that novel neuropeptides such as phoenixin (PNX), spexin (SPX), and kisspeptin (KISS) are involved in the pathogenesis of eating disorders. The study presented here analyzed neuropeptide concentrations during the course of anorexia nervosa (AN) and aimed to correlate those values with anthropometric and psychometric measurements. METHODS: A longitudinal study was carried outin 30 AN adolescent patients and 15 age-matched healthy female controls. Selected neuroprotein serum levels were analyzed in malnourished patients (accAN) and following partial weight recovery (norAN), and these values were compared with the control group. RESULTS: In accAN patients, decreased serum PNX levels were detected while SPX serum concentrations were lower in the accAN and norAN patients. No differences were observed in KISS concentrations in all studied groups. CONCLUSIONS: In malnourished adolescent inpatients with AN, serum PNX and SPX level were decreased. The partial weight recovery normalized PNX concentrations but failed to normalize SPX levels. Therefore these two neuropeptides might be crucial for the etiology and course of the AN. The KISS levels did not change in the course of AN. The PNX levels were associated with some symptoms of eating disorders which may indicate its potential contribution in the regulation of emotions and behaviors in AN.


Anorexia Nervosa , Kisspeptins/blood , Neuropeptides , Peptide Hormones/blood , Adolescent , Anorexia Nervosa/psychology , Female , Humans , Inpatients , Longitudinal Studies , Neuropeptides/blood
6.
Psychiatr Pol ; 54(2): 209-222, 2020 Apr 30.
Article En, Pl | MEDLINE | ID: mdl-32772055

The vast majority of new neuropeptides feature unique biochemical properties as well as awide spectrum of physiological activity applied in numerous neuronal pathways, including hypothalamus and the limbic system. Special interest should be paid to nesfatin-1 - the relatively recently discovered and still intensively studied regulatory factor and a potential modulator of eating behaviors. New information about it now allows to consider this neuropeptide as a potentially important factor involved in the pathogenesis of many different mental disorders. The considered pharmacomodulation of nesfatinergic signaling may be potentially helpful in the future treatment of some neuropsychiatric and metabolic disorders including anorexia nervosa. Although the results of some basic and clinical tests seem to be promising, all possible applications of the aforementioned neuropeptides, together with their agonists and antagonists still remain in the area of speculation. The intensive search of selective modulators of their known receptors may facilitate the opening of a promising chapter in the eating disorders therapy. This paper provides a review of recent scientific reports regarding the hypothetical role of nesfatin-1 in the neuronal pathways related to pathophysiology of anorexia nervosa.


Appetite Regulation/physiology , Feeding and Eating Disorders/metabolism , Neuropeptides/metabolism , Nucleobindins/metabolism , Anorexia Nervosa/metabolism , Humans , Hypothalamus/metabolism , Immunohistochemistry , Nervous System Physiological Phenomena , Neurochemistry , Neuropeptide Y/metabolism
7.
J Ethnopharmacol ; 262: 113159, 2020 Nov 15.
Article En | MEDLINE | ID: mdl-32736052

ETHNOPHARMACOLOGICAL RELEVANCE: The history of medical application of propolis (also known as bee glue) dates back to the times of ancient Greeks, Romans, Persians and Egyptians. Honey and other bee products, including propolis, occupy an important place in Polish folk medicine. Scientific research on propolis in Poland began in the early 1960s in Zabrze and continues until now. AIM OF THE REVIEW: The aim of this review is to provide an overview of information on Polish research on propolis and its medical application with particular emphasis on studies concerning wound healing. Consequently, our goal is also to shed a new light on therapeutic potential of Polish propolis in order to support future research in the field. MATERIALS AND METHODS: A systematic review of scientific literature on propolis and its medical application was performed by using the literature databases (PubMed, Web of Science, Google Scholar). We paid special attention to papers describing the effect of propolis on skin wound healing as well as to Polish contribution to research on propolis. RESULTS: Professor Stan Scheller was the first Polish scientist dealing with propolis and its medical potential. His legacy was continued by several research teams that studied the topic in various aspects. They analyzed propolis composition, its antioxidant, anti-inflammatory, antimicrobial, antiapoptotic and anticancer properties as well as its application in dentistry and wound treatment. Burn wound healing physiology after propolis administration was thoroughly studied on pig model, whereas research on patients proved the efficacy of propolis in chronic venous leg ulcer treatment. CONCLUSION: Polish scientists have made a significant contribution to the research on propolis, its biological properties and influence on wound healing. Propolis ointments can effectively accelerate the healing process and improve healing physiology, so they can be recommended as a promising topical medication for wound treatment in the future clinical and preclinical trials.


Anti-Infective Agents/administration & dosage , Biomedical Research/methods , Medicine, Traditional/methods , Propolis/administration & dosage , Wound Healing/drug effects , Animals , Anti-Infective Agents/isolation & purification , Bees , Biomedical Research/trends , Honey , Humans , Medicine, Traditional/trends , Poland/ethnology , Propolis/isolation & purification , Wound Healing/physiology
8.
Int Wound J ; 17(2): 491-507, 2020 Apr.
Article En | MEDLINE | ID: mdl-31943788

Unique properties of amniotic membrane make it a promising source for tissue engineering and a clinically useful alternative for patients suffering from chronic wounds including, for example, ulcers, burns, ocular surface damages and wounds occurring in the course of bullous diseases like stevens-johnson syndrome and toxic epidermal necrolysis. Its use has many advantages over standard wound care, as it contains pluripotent cells, nutrients, anti-fibrotic and anti-inflammatory cytokines, growth factors and extracellular matrix (ECM) proteins. Placental tissues can be prepared as a medical component, an advanced therapy medicinal product or a tissue graft. In addition to basic preparation procedures such as washing, rinsing, cutting, drying and sterilisation, there are many optional steps such as perforation, crosslinking and decellularisation. Finally, transplants should be properly stored-in cryopreserved or dehydrated form. In recent years, many studies including basic science and clinical trials have proven the potential to expand the use of amniotic membrane and amnion-derived cells to the fields of orthopaedics, dentistry, surgery, urology, vascular tissue engineering and even oncology. In this review, we discuss the role of placental tissues in skin wound healing and in the treatment of various diseases, with particular emphasis on bullous diseases. We also describe some patented procedures for placental tissue grafts preparation.


Amnion/transplantation , Skin Diseases, Vesiculobullous/surgery , Stevens-Johnson Syndrome/surgery , Transplants , Wound Healing , Female , Humans , Pregnancy
9.
Eur J Pharmacol ; 843: 307-315, 2019 Jan 15.
Article En | MEDLINE | ID: mdl-30537490

The latest findings indicate the huge therapeutic potential of stem cells in regenerative medicine, including the healing of chronic wounds. Main stem cell types involved in wound healing process are: epidermal and dermal stem cells, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and hematopoietic stem cells (HSCs). In the therapy of chronic wounds, they can be administrated either topically or using different matrix like hydrogels, scaffolds, dermal substitutes and extracellular matrix (ECM) derivatives. Stem cells are proven to positively influence wound healing by different direct and indirect mechanisms including residing cells stimulation, biomolecules release, inflammation control and ECM remodelling. MSCs are especially worth mentioning as they can be easily derived from bone-marrow or adipose tissue. Apart from traditional approach of administering living stem cells to wounds, new trends have emerged in recent years. Good healing results are obtained using stem cell secretome alone, for example exosomes or conditioned media. There are also attempts to improve healing potential of stem cells by their co-culture with other cell types as well as by their genetic modifications or pretreatment using different chemicals or cell media. Moreover, stem cells have been tested for novel therapeutic purposes like for example acute burns and have been used in experiments on large animal models including pigs and sheep. In this review we discuss the role of stem cells in skin wound healing acceleration. In addition, we analyse possible new strategies of stem cells application in treatment of chronic wounds.


Stem Cell Transplantation/trends , Wound Healing , Animals , Humans , Skin/injuries
10.
CNS Neurol Disord Drug Targets ; 17(6): 458-463, 2018.
Article En | MEDLINE | ID: mdl-29952270

BACKGROUND & OBJECTIVE: Continuously active neurogenic regions in the adult brain are located in the subventricular zone (SVZ) of the lateral ventricles and subgranular zone of the hippocampal dentate gyrus. Neurogenesis is modulated by many factors such as growth factors, neurotransmitters and hormones. Neuropsychiatric drugs, especially antidepressants, mood stabilizers and antipsychotics may also affect the origin of neuronal cells. METHOD: The purpose of this study was to determine the effects of chronic olanzapine treatment on adult rat neurogenesis at the level of the SVZ. The number of neuroblasts was evaluated using immunohistochemical and fluorescent detection of sex determining region Y-box 2 and doublecortin expressing cells. RESULTS & CONCLUSION: The results indicate that olanzapine has proneurogenic effects on the adult rat SVZ, as the mean number of sex determining region Y-box 2 and doublecortin-positive cells increased significantly, while there was a similar tendency in the subgranular zone. Collectively, these results suggest that long-term treatment with olanzapine may stimulate neurogenic stem cell formation in the SVZ which supports adult neurogenesis.


Antipsychotic Agents/pharmacology , Lateral Ventricles/cytology , Microtubule-Associated Proteins/metabolism , Neurogenesis/drug effects , Neurons/drug effects , Neuropeptides/metabolism , Olanzapine/pharmacology , SOXB1 Transcription Factors/metabolism , Animals , Doublecortin Domain Proteins , Doublecortin Protein , Lateral Ventricles/drug effects , Male , Rats , Rats, Sprague-Dawley
11.
J Neural Transm (Vienna) ; 125(7): 1099-1105, 2018 07.
Article En | MEDLINE | ID: mdl-29488100

Neuroleptics modulate the expression level of some regulatory neuropeptides in the brain. However, if these therapeutics influence the peptidergic circuits in the amygdala remains unclear. This study specifies the impact profile of the classical antipsychotic drugs on mRNA expression of the spexin/NPQ, kisspeptin-1 and POMC in the rat amygdala. Animals were treated with haloperidol and chlorpromazine for 28 days prior to transcript quantification via qPCR. Haloperidol and chlorpromazine induced a change in the expression of all neuropeptides analyzed. Both drugs led to the decrease of Kiss-1 expression, whereas in POMC and spexin/NPQ their up-regulation in the amygdala was detected. These modulating effects on may represent alternative, so far unknown mechanisms, of classical antipsychotic drugs triggering pharmacological responses.


Amygdala/drug effects , Antipsychotic Agents/pharmacology , Kisspeptins/drug effects , Peptide Hormones/drug effects , Pro-Opiomelanocortin/drug effects , Amygdala/metabolism , Animals , Gene Expression/drug effects , Kisspeptins/biosynthesis , Male , Peptide Hormones/biosynthesis , Pro-Opiomelanocortin/biosynthesis , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley
12.
Pharmacopsychiatry ; 50(1): 32-37, 2017 Jan.
Article En | MEDLINE | ID: mdl-27388714

Introduction: Kisspeptin has a multidirectional neuroendocrinal activity. It is especially considered to be a central regulator of reproductive function. Numerous data proved that neuroleptic administration may affect the peptidergic signaling in the various brain structures. However, there is no information concerning the relationship between treatment with neuroleptics and brain kisspeptin mRNA expression. Methods: We assessed the kisspeptin mRNA level in the hypothalamus and hippocampus of rats shortly and chronically (28 days) treated with haloperidol, chlorpromazine, and olanzapine using a quantitative Real-Time PCR method. Results: We have shown that all studied neuroleptics injected chronically have the ability to downregulate the kisspeptin mRNA expression in the hypothalamus, which may suggest the presence of an alternative mechanism for their orexigenic side effects. Long-term treatment with chlorpromazine increased the level of kisspeptin mRNA expression in the hippocampus. Discussion: Our results shed a new light on the pharmacology of antipsychotics and may contribute to a better understanding of alternative mechanisms responsible for their action. The study also highlights a complex nature of potential connections between dopamine transmission and brain kisspeptin pathways.


Antipsychotic Agents/pharmacology , Hippocampus/drug effects , Hypothalamus/drug effects , Kisspeptins/genetics , RNA, Messenger/metabolism , Animals , Hippocampus/metabolism , Hypothalamus/metabolism , Kisspeptins/metabolism , Male , Rats , Rats, Sprague-Dawley , Time Factors
13.
Pharmacol Rep ; 68(6): 1326-1331, 2016 Dec.
Article En | MEDLINE | ID: mdl-27710862

BACKGROUND: Spexin (SPX) is a recently discovered neuropeptide that exhibits a large spectrum of central and peripheral regulatory activity, especially when considered as a potent anorexigenic factor. It has already been proven that antidepressants, including selective serotonin reuptake inhibitors (SSRI), can modulate peptidergic signaling in various brain structures. Despite these findings, there is so far no information regarding the influence of treatment with the SSRI antidepressant escitalopram on brain SPX expression. METHODS: In this current study we measured SPX mRNA and protein expression in the selected brain structures (hypothalamus, hippocampus and striatum) of rats chronically treated with a 10mg/kg dose of escitalopram using quantitative Real-Time PCR and immunohistochemistry. RESULTS: Strikingly, long-term (4 week) drug treatment led to the downregulation of SPX expression in the rat hypothalamus. This supports the hypothesis that SPX may be involved in the hypothalamic serotonin-dependent actions of SSRI antidepressants and possibly also in the central mechanism of body mass increase. Conversely, SPX expression increased in the hippocampus and striatum. CONCLUSIONS: This is the first report of the effects of a neuropsychiatric medication on SPX expression in animal brain. Our findings shed a new light on the pharmacology of antidepressants and may contribute to a better understanding of the alternative mechanisms responsible for antidepressant action.


Citalopram/pharmacology , Corpus Striatum/drug effects , Hippocampus/drug effects , Hypothalamus/drug effects , Peptide Hormones/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology , Animals , Corpus Striatum/metabolism , Gene Expression Regulation , Hippocampus/metabolism , Hypothalamus/metabolism , Male , Peptide Hormones/antagonists & inhibitors , Peptide Hormones/genetics , Rats , Rats, Sprague-Dawley
14.
Pharmacol Rep ; 68(5): 990-5, 2016 Oct.
Article En | MEDLINE | ID: mdl-27391358

BACKGROUND: This study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon. METHODS: To explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed. RESULTS: Interestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex. CONCLUSIONS: Neuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico-striato-thalamo-cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.


Antipsychotic Agents/pharmacology , Diencephalon/drug effects , N-Methylaspartate/metabolism , Neocortex/drug effects , Protein Subunits/metabolism , Animals , Benzodiazepines/pharmacology , Clozapine/pharmacology , Diencephalon/metabolism , Down-Regulation/drug effects , Haloperidol/pharmacology , Hippocampus/drug effects , Hippocampus/metabolism , Hypothalamus/drug effects , Male , Neocortex/metabolism , Olanzapine , Rats , Rats, Sprague-Dawley , Up-Regulation/drug effects
15.
Pharmacol Rep ; 68(2): 292-6, 2016 Apr.
Article En | MEDLINE | ID: mdl-26922530

BACKGROUND: Neuropeptides play an important role in various neural pathways, being able to control a wide spectrum of physiological responses. Neuropeptide Y (NPY) and proopiomelanocortin (POMC) functions are quite well studied, however little is known about their action at the level of limbic structures. The present work was focused on the expression of the aforementioned peptides in this brain structure of rats treated with olanzapine, a second generation neuroleptic drug. The detailed purpose of this experiment was the evaluation of potential relationships between chronic olanzapine administration and NPY and POMC mRNA expression in the amygdala and hippocampal formation. METHODS: The studies were carried out on adult, male Sprague-Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28 day-long intraperitoneal injection). All individuals were sacrificed under anaesthesia, then the amygdaloid complexes and hippocampi were excised. Total mRNA was isolated from homogenized samples of both structures and the RT-PCR method was used for estimation of NPY and POMC gene relative expression. RESULTS: Prolonged olanzapine administration is reflected in qualitatively different changes in expression of NPY and POMC mRNA in the rat amygdala and hippocampus. Interestingly enough, olanzapine did not affect NPY expression, but significantly increased the POMC level in both examined regions. CONCLUSIONS: Olanzapine can affect amygdalar and hippocampal neuronal populations by the modulation of neuropeptide activity. Importantly, it may suggest the existence of an alternative mode of its action. Undoubtedly this hypothetic regulatory mechanism requires further pharmacological and neurostructural study.


Amygdala/drug effects , Benzodiazepines/administration & dosage , Hippocampus/drug effects , Neuropeptide Y/genetics , Pro-Opiomelanocortin/genetics , RNA, Messenger/genetics , Animals , Gene Expression/drug effects , Male , Olanzapine , Rats , Rats, Sprague-Dawley
16.
Acta Neuropsychiatr ; 28(2): 110-6, 2016 Apr.
Article En | MEDLINE | ID: mdl-26467816

OBJECTIVE: The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression. METHODS: We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction. RESULTS: Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum. CONCLUSIONS: This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.


Brain/drug effects , Brain/metabolism , Gene Expression Regulation/drug effects , Haloperidol/pharmacology , Neuropeptides/genetics , Receptors, Neuropeptide/genetics , Animals , Brain Stem/drug effects , Brain Stem/metabolism , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Down-Regulation/drug effects , Down-Regulation/genetics , Hippocampus/drug effects , Hippocampus/metabolism , Male , Rats , Up-Regulation/drug effects , Up-Regulation/genetics
17.
Pharmacol Rep ; 67(6): 1208-14, 2015 Dec.
Article En | MEDLINE | ID: mdl-26481544

BACKGROUND: Among many factors influencing adult neurogenesis, pharmacological modulation has been broadly studied. It is proven that neuroleptics positively affect new neuron formation in canonical neurogenic sites - subgranular zone of the hippocampal dentate gyrus and subventricular zone of the lateral ventricles. Latest findings suggest that adult neurogenesis also occurs in several additional regions like the hypothalamus, amygdala, neocortex and striatum. As the hypothalamus is considered an important target of neuroleptics, a hypothesis can be made that these substances are able to modulate local neural proliferation. METHODS: Experiments were performed on adult male rats injected for 28 days or 1 day by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Immunohistochemistry was used to determine expression of proliferation marker (Ki-67) and the marker of neuroblasts - doublecortin (DCX) - which may inform about drug influence on adult neurogenesis at the level of the hypothalamus. RESULTS: It was shown that a single injection of antipsychotics causes significant decrease in hypothalamic DCX expression, but after chronic treatment with chlorpromazine, but not olanzapine, there is an increase in the number of newly formed neuroblasts. Haloperidol has the opposite effect - its long-term administration decreases the number of DCX-positive cells. Cell proliferation levels (Ki-67 expression) increase after long-term drug administration, whereas their single doses do not have any modulatory effect on proliferation potential. CONCLUSIONS: Our results throw a new light on the neuroleptics mechanism of action. They also support the potential role of antipsychotics as a factor that can modulate hypothalamic neurogenesis with putative clinical applications.


Antipsychotic Agents/pharmacology , Chlorpromazine/pharmacology , Haloperidol/pharmacology , Hypothalamus/cytology , Hypothalamus/drug effects , Neurogenesis/drug effects , Neurons/drug effects , Animals , Benzodiazepines/pharmacology , Doublecortin Protein , Male , Olanzapine , Rats
18.
J Mol Neurosci ; 57(3): 352-7, 2015 Nov.
Article En | MEDLINE | ID: mdl-26227793

Neuropeptide S (NPS) has a multidirectional regulatory activity, especially when considered as a potent endogenous anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signaling in various brain structures. However, there is no information regarding the influence of treatment with antipsychotics on brain NPS expression. In the current study, we assessed the NPS and NPS receptor (NPSR) mRNA levels in the brains of rats shortly and chronically treated with chlorpromazine and olanzapine using quantitative real-time PCR. Both single-dose and long-term (4 months) olanzapine treatment led to the upregulation of NPS expression in the rat hypothalamus. It supports the hypothesis that NPS is involved in the dopamine-dependent anxiolytic actions of selected neuroleptics and possibly also in the pathophysiology of mental disorders. On the other hand, NPSR expression decreased after single-dose and chronic chlorpromazine administration in the hypothalamus, as well as after chronic olanzapine and chlorpromazine administration in the striatum and hippocampus. These results cast a new light on the pharmacology of antipsychotics and contribute to a better understanding of the mechanisms responsible for their action. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.


Antipsychotic Agents/pharmacology , Benzodiazepines/pharmacology , Chlorpromazine/pharmacology , Corpus Striatum/drug effects , Hippocampus/drug effects , Hypothalamus/drug effects , Neuropeptides/biosynthesis , RNA, Messenger/biosynthesis , Receptors, Neuropeptide/biosynthesis , Animals , Antipsychotic Agents/administration & dosage , Benzodiazepines/administration & dosage , Chlorpromazine/administration & dosage , Corpus Striatum/metabolism , Dopamine/physiology , Gene Expression Regulation/drug effects , Hippocampus/metabolism , Hypothalamus/metabolism , Male , Neuropeptides/genetics , Olanzapine , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Receptors, Dopamine/physiology , Receptors, Neuropeptide/genetics
19.
Neuropeptides ; 51: 31-42, 2015 Jun.
Article En | MEDLINE | ID: mdl-25888224

Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experiments were carried out on adult male Sprague-Dawley rats injected intraperitoneally for 1 day or for 28 days by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform PCR reactions and also whole brains were sliced for immunohistochemical analysis. We assessed the expression of orexigenic/anorexigenic neuropeptides and their receptors--neuropeptide Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin receptor type 4 (MC4R)--both on the mRNA and protein levels. We have shown that antipsychotics of different generations administered chronically have the ability to upregulate PPOX, orexin A and Y1R expression with little or no effect on orexigenic receptors (OX1R, OX2R) and NPY. Interestingly, antipsychotics also increased the level of some anorexigenic factors (POMC, α-MSH and MC4R), but at the same time strongly downregulated NUCB2 and nesfatin-1 signaling--a newly discovered neuropeptide known as a food-intake inhibiting factor. Our results may contribute to a better understanding of mechanisms responsible for antipsychotics' side effects. They also underline the complex nature of interactions between classical monoamine receptors and hypothalamic peptidergic pathways, which has potential clinical applications.


Antipsychotic Agents/pharmacology , Hypothalamus/drug effects , Hypothalamus/metabolism , Animals , Benzodiazepines/pharmacology , Calcium-Binding Proteins/metabolism , Chlorpromazine/pharmacology , DNA-Binding Proteins/metabolism , Drug Administration Schedule , Haloperidol/pharmacology , Male , Nerve Tissue Proteins/metabolism , Neuropeptide Y/metabolism , Nucleobindins , Olanzapine , Orexin Receptors/metabolism , Orexins/metabolism , Pro-Opiomelanocortin/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Melanocortin, Type 4/metabolism , Receptors, G-Protein-Coupled/metabolism , Receptors, Neuropeptide/metabolism , alpha-MSH/metabolism
20.
Neurosci Lett ; 592: 17-21, 2015 Apr 10.
Article En | MEDLINE | ID: mdl-25736948

The hypothalamus regulates a number of autonomic functions essential for homeostasis; therefore, investigations concerning hypothalamic neuropeptides and their functions and distribution are of great importance in contemporary neuroscience. Recently, novel regulatory factors expressed in the hypothalamus have been discovered, of which nesfatin-1 and phoenixin (PNX), show intriguing similarities in their brain distributions. There are currently few studies characterizing PNX expression, so it is imperative to accurately trace its localization, with particular attention to the hypothalamic nuclei and nesfatin-1 co-expression. Using fluorescence and classical immunohistochemical stainings on adult rat brain, we visualized the potential co-expression of nesfatin-1 and PNX immunoreactive cells. We have demonstrated a distinct PNX-immunoreactivity in 21-32% of cells in the arcuate nucleus, paraventricular nucleus, ventromedial and lateral hypothalamus. Nesfatin-1 expression reached 45-68% of all neurons in the same sites, while co-expression was strikingly seen in the vast majority (70-86%) of PNX-immunoreactive neurons in the rat hypothalamic nuclei. Our results demonstrate for the first time, a wide distribution of PNX in the hypothalamus which could implicate a potential functional relationship with nesfatin-1, possibly in the regulation of the hypothalamic-pituitary-gonadal axis or other autonomic functions, which require further study.


Calcium-Binding Proteins/metabolism , DNA-Binding Proteins/metabolism , Hypothalamic Hormones/metabolism , Hypothalamus/metabolism , Nerve Tissue Proteins/metabolism , Peptide Hormones/metabolism , Animals , Immunohistochemistry , Male , Neurons/metabolism , Nucleobindins , Rats, Sprague-Dawley
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