Publications by authors named "Ewa Poleszak"

132 Publications

Nasal carriage of Staphylococcus aureus in children with grass pollen-induced allergic rhinitis and the effect of polyvalent mechanical bacterial lysate immunostimulation on carriage status: A randomized controlled trial.

Immun Inflamm Dis 2021 Dec 29. Epub 2021 Dec 29.

Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland.

Background: Numerous studies indicate that Staphylococcus aureus (S. aureus) colonizing the nasal cavity plays a role in the pathogenesis of allergic rhinitis (AR). This bacterium is able to produce a variety of toxins with superantigenic properties that can exacerbate allergic inflammation.

Objective: The objective of the study was to evaluate the ability of polyvalent mechanical bacterial lysate (PMBL) to eliminate S. aureus nasal carriage in children with grass pollen-induced AR.

Methods: This randomized, double-blind, placebo-controlled study included 80 children aged 5-17 years with seasonal AR (SAR). At the randomization visit and after 12 weeks of the study, a swab was taken from the region of the middle nasal meatus. Standard microbiology culture and identification techniques were used to analyze the swab contents.

Results: Nasal colonization by S. aureus was confirmed in 29 children (42%), with Moraxella catarrhalis in three participants (4.4%). Physiological flora was detected in 37 children. No statistically significant differences were observed between the two measurement points in both the PMBL and placebo groups with respect to the number of patients whose nasal swab cultures showed a growth of S. aureus (p = 1). Both groups also showed no significant changes in the mean number of S. aureus colonies in nasal swab cultures taken at baseline and after 12 weeks of the study (PMBL group p = .41; placebo group p = .16).

Conclusion: Almost every second child with SAR is S. aureus nasal carrier. Sublingual administration of PMBL in children with grass pollen-induced AR did not affect S. aureus nasal colonization. Therefore, PMBL should not be used for the eradication of S. aureus from the nasal cavity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/iid3.584DOI Listing
December 2021

Influence of Incorporation of Different d-Electron Metal Cations into Biologically Active System on Its Biological and Physicochemical Properties.

Int J Mol Sci 2021 Nov 29;22(23). Epub 2021 Nov 29.

Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

Three new compounds, namely [HL][CuCl], [HL][ZnCl], and [HL][CdCl] () were synthesized and their physicochemical and biological properties were thoroughly investigated. All three compounds form isostructural, crystalline systems, which have been studied using Single-Crystal X-ray diffraction analysis (SC-XRD) and Fourier-transform infrared spectroscopy (FTIR). The thermal stability was investigated using thermogravimetric analysis (TGA) and melting points for all compounds have been determined. Magnetic measurements were performed in order to study the magnetic properties of the compounds. The above mentioned techniques allowed us to comprehensively examine the physicochemical properties of the newly obtained compounds. The biological activity was investigated using the number of Zebrafish tests, as it is one of the most common models for studying the impact of newly synthesized compounds on the central nervous system (CNS), since this model is very similar to the human CNS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms222312909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657940PMC
November 2021

Influence of (Yacon) on the Activity of Antidepressant Drugs in Mice.

Life (Basel) 2021 Oct 21;11(11). Epub 2021 Oct 21.

Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.

Depression is one of the most common mental disorders in the world that negatively affects the daily functioning of patients. Numerous studies are currently being conducted to examine the antidepressant potential of innovative synthetic compounds and herbal substances. Yacon, , belongs to plants with numerous health-beneficial properties. Yacon-based products are regarded as a functional food. In our study, we attempted to check whether administration of Yacon tuber extract would have an antidepressant effect in the forced swim test (FST) in mice and whether its intake could influence the activity of conventional antidepressant drugs with different mechanisms of action, i.e., imipramine hydrochloride, fluoxetine hydrochloride, and reboxetine mesylate. The spontaneous locomotor activity of the tested mice was also investigated to eliminate any false-positive results. We demonstrated that an intragastric administration of the Yacon tuber extract at a dose of 100 mg/kg induced the antidepressant-like behavior in the FST in mice and that a combined administration of the sub-effective doses of the Yacon extract (50 mg/kg) with imipramine hydrochloride (7.5 mg/kg), fluoxetine hydrochloride (20 mg/kg), or reboxetine mesylate (5 mg/kg) significantly reduced the immobility time of animals in this behavioral test. The obtained results were not affected by the increased locomotor activity of the tested subjects. In conclusion, our findings suggest that Yacon tuber extract is promising as an alternative mood-improving product since it possesses an antidepressant potential and it can acts synergistically with conventional antidepressant drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life11111117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624190PMC
October 2021

The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.

Pharmacol Res 2021 10 24;172:105840. Epub 2021 Aug 24.

Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033 Lublin, Poland. Electronic address:

Emerging evidence indicates that the gut microbiota play a crucial role in the bidirectional communication between the gut and the brain suggesting that the gut microbes may shape neural development, modulate neurotransmission and affect behavior, and thereby contribute to the pathogenesis and/or progression of many neurodevelopmental, neuropsychiatric, and neurological conditions. This review summarizes recent data on the role of microbiota-gut-brain axis in the pathophysiology of neuropsychiatric and neurological disorders including depression, anxiety, schizophrenia, autism spectrum disorders, Parkinson's disease, migraine, and epilepsy. Also, the involvement of microbiota in gut disorders co-existing with neuropsychiatric conditions is highlighted. We discuss data from both in vivo preclinical experiments and clinical reports including: (1) studies in germ-free animals, (2) studies exploring the gut microbiota composition in animal models of diseases or in humans, (3) studies evaluating the effects of probiotic, prebiotic or antibiotic treatment as well as (4) the effects of fecal microbiota transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105840DOI Listing
October 2021

Effect of Ellagic Acid on Seizure Threshold in Two Acute Seizure Tests in Mice.

Molecules 2021 Aug 10;26(16). Epub 2021 Aug 10.

Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sklodowska University, Akademicka 19, PL 20-033 Lublin, Poland.

Ellagic acid (EA) is a natural dietary polyphenol that has many beneficial properties, including anti-inflammatory, antioxidant, antiviral, antibacterial, and neuroprotective effects. Studies have revealed that EA may modulate seizure activity in chemically induced animal models of seizures. Therefore, the aim of the present study was to investigate the effect of EA on the seizure threshold in two acute seizure tests in male mice, i.e., in the intravenous (i.v.) pentylenetetrazole (PTZ) seizure test and in the maximal electroshock seizure threshold (MEST) test. The obtained results showed that EA (100 mg/kg) significantly elevated the threshold for both the first myoclonic twitch and generalized clonic seizure in the i.v. PTZ seizure test. At the highest dose tested (200 mg/kg), EA increased the threshold for tonic hindlimb extension in the MEST test. EA did not produce any significant changes in motor coordination (assessed in the chimney test) or muscular strength (investigated in the grip-strength test). The plasma and total brain concentration-time profiles of EA after intraperitoneal and oral administration were also determined. Although further studies are necessary to confirm the anticonvulsant activity of EA, our findings suggest that it may modulate seizure susceptibility in animal models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26164841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398784PMC
August 2021

Effects of new antiseizure drugs on seizure activity and anxiety-like behavior in adult zebrafish.

Toxicol Appl Pharmacol 2021 09 27;427:115655. Epub 2021 Jul 27.

Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sklodowska University, Akademicka 19, PL 20-033 Lublin, Poland. Electronic address:

Several studies with larvae and adult zebrafish have shown that old and new antiseizure drugs (ASDs) produce discrepant results in seizure tests, locomotor activity or anxiety models. In this study, the pentylenetetrazole seizure test (PTZ) was performed to assess the effectiveness of four new ASDs: lamotrigine (LTG), topiramate (TPM), felbamate (FBM), and levetiracetam (LEV) in the subsequent stages of seizures in adult fish. All ASDs were administered intraperitoneally (i.p.). The time of maximal anticonvulsant effect and the dose-response relationship of the drugs were assessed. The effects of studied ASDs on the locomotor activity and the anxiety-like behavior in the color preference test were also investigated. Furthermore, drug concentrations in zebrafish homogenates were determined. LTG, TPM, and LEV significantly increased the seizure latency at three subsequent stages of seizures (SI-SIII), while FBM was effective only at SI. Locomotor activity decreased after TPM treatment. TPM and FBM exhibited a strong anxiolytic-like effect in the color preference test. LEV at the highest dose tested had a weak anxiolytic-like effect. The HPLC analysis showed average concentrations of the studied ASDs in the fish body during their maximum anticonvulsant activity. The present study shows that FBM cannot inhibit all subsequent PTZ seizure stages in the adult fish. Except for LTG, the studied drugs affected the anxiety-like behavior of treated animals. Furthermore, only TPM significantly changed locomotion parameters. Our findings support the need to accurately characterize the efficacy of new ASDs at different stages of the PTZ-induced seizures in adult zebrafish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.taap.2021.115655DOI Listing
September 2021

Pharmaco-Electroencephalography-Based Assessment of Antidepressant Drug Efficacy-The Use of Magnesium Ions in the Treatment of Depression.

J Clin Med 2021 Jul 15;10(14). Epub 2021 Jul 15.

Department of Psychiatry, Medical University of Warsaw, 00-665 Warsaw, Poland.

Pharmaco-electroencephalography (pharmaco-EEG) is a technique used to assess the effects of psychotropic medications on the bioelectrical activity of the brain. The purpose of this study was to assess the treatment response with the use of the Hamilton Depression Rating Scale (HDRS) and via EEG. Over an 8-week period, we analyzed electroencephalographic tracings of 91 patients hospitalized for major depression at the Medical University of Warsaw. Thirty-nine of those patients received tricyclic antidepressants (TCAs), 35 received fluoxetine, and 17 received fluoxetine augmented with magnesium (Mg) ions. All patients had their serum drug levels monitored. The highest proportion of patients (88.2%) who showed adequate responses to treatment was observed in the fluoxetine+Mg group, whereas the lowest rates of treatment response were observed in the TCA group (58.3%). This difference was statistically significant ( = 0.029, Phi = 0.30). Our study demonstrated a relationship between achieving remission (HDRS ≤ 6 at week 8 of treatment) and obtaining a positive pharmaco-EEG profile 6 h after administration of the first dose in the group receiving fluoxetine augmented with Mg ions ( = 0.035, Phi = 0.63).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10143135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306926PMC
July 2021

The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Clinic of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005 Warsaw, Poland.

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1β, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T-H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22115853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198845PMC
May 2021

The Interaction of Selective A1 and A2A Adenosine Receptor Antagonists with Magnesium and Zinc Ions in Mice: Behavioural, Biochemical and Molecular Studies.

Int J Mol Sci 2021 Feb 12;22(4). Epub 2021 Feb 12.

Chair and Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, 1 Chodźki Street, PL 20-093 Lublin, Poland.

The purpose of the study was to investigate whether the co-administration of Mg and Zn with selective A1 and A2A receptor antagonists might be an interesting antidepressant strategy. Forced swim, tail suspension, and spontaneous locomotor motility tests in mice were performed. Further, biochemical and molecular studies were conducted. The obtained results indicate the interaction of DPCPX and istradefylline with Mg and Zn manifested in an antidepressant-like effect. The reduction of the BDNF serum level after co-administration of DPCPX and istradefylline with Mg and Zn was noted. Additionally, Mg or Zn, both alone and in combination with DPCPX or istradefylline, causes changes in expression, DPCPX or istradefylline co-administered with Zn increases expression as compared to a single-drug treatment, co-administration of tested agents does not have a more favourable effect on expression. Moreover, the changes obtained in , , expression show that DPCPX-Mg, DPCPX-Zn, istradefylline-Mg and istradefylline-Zn co-treatment may have greater antioxidant capacity benefits than administration of DPCPX and istradefylline alone. It seems plausible that a combination of selective A1 as well as an A2A receptor antagonist and magnesium or zinc may be a new antidepressant therapeutic strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22041840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918707PMC
February 2021

Purinergic transmission in depressive disorders.

Pharmacol Ther 2021 08 17;224:107821. Epub 2021 Feb 17.

Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033 Lublin, Poland. Electronic address:

Purinergic signaling involves the actions of purine nucleotides and nucleosides (such as adenosine) at P1 (adenosine), P2X, and P2Y receptors. Here, we present recent data contributing to a comprehensive overview of the association between purinergic signaling and depression. We start with background information on adenosine production and metabolism, followed by a detailed characterization of P1 and P2 receptors, with an emphasis on their expression and function in the brain as well as on their ligands. We provide data suggestive of altered metabolism of adenosine in depressed patients, which might be regarded as a disease biomarker. We then turn to considerable amount of preclinical/behavioral data obtained with the aid of the forced swim test, tail suspension test, learned helplessness model, or unpredictable chronic mild stress model and genetic activation/inactivation of P1 or P2 receptors as well as nonselective or selective ligands of P1 or P2 receptors. We also aimed to discuss the reason underlying discrepancies observed in such studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pharmthera.2021.107821DOI Listing
August 2021

Asiatic Acid, a Natural Compound that Exerts Beneficial Effects on the Cystometric and Biochemical Parameters in the Retinyl Acetate-Induced Model of Detrusor Overactivity.

Front Pharmacol 2020 29;11:574108. Epub 2021 Jan 29.

Chair and Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, Lublin, Poland.

Scientists have been constantly looking for new synthetic and natural compounds that could have beneficial effects in bladder overactivity. Our attention was drawn by asiatic acid that influences a number of molecules and signaling pathways relevant for the proper functioning of the urinary tracts in humans. In the present project we wanted to check whether asiatic acid would have positive effects in the confirmed animal model of detrusor overactivity (DO) and whether it would affect the bladder blood flow, urothelium thickness, inflammatory and oxidative stress markers, neurotrophic and growth factors, and other parameters important for the activity of the urinary bladder. The outcomes of our study showed that a 14-day administration of asiatic acid (30 mg/kg/day) by oral gavage normalizes the cystometric parameters corresponding to DO and reduces the accompanying oxidative stress (measured by the levels of malondialdehyde-61,344 ± 24,908 pg/ml vs. 33,668 ± 5,071 pg/ml, 3-nitrotyrosine-64,615 ± 25,433 pg/ml vs. 6,563 ± 1,736 pg/ml, and NOS2-2,506 ± 411.7 vs. 3,824 ± 470.1 pg/ml). Moreover, it decreases the urinary secretion of neurotrophins (BDNF-304.4 ± 33.21 pg/ml vs. 119.3 ± 11.49 pg/ml and NGF-205.5 ± 18.50 vs. 109.7 ± 15.94 pg/ml) and prevents the changes in a range of biomarkers indicating the dysfunction of the urinary bladder, CGRP (421.1 ± 56.64 vs. 108.1 ± 11.73 pg/ml), E-Cadherin (773.5 ± 177.5 pg/ml vs. 1,560 ± 154.5 pg/ml), OCT3 (3,943 ± 814.6 vs. 1,018 ± 97.07 pg/ml), SNAP-23 (6,763 ± 808.9 pg/ml vs. 3,455 ± 554.5 pg/ml), SNAP-25 (2,038 ± 162.7 pg/ml vs. 833.3 ± 65.48), substance P (171.7 ± 16.86 pg/ml vs. 65.07 ± 8.250 pg/ml), SV2A (1,927 ± 175.3 pg/ml vs. 1,154 ± 254.9 pg/ml), tight junction protein 1 (360.1 ± 95.05 pg/ml vs. 563.4 ± 65.43 pg/ml), VAChT (16,470 ± 2,419 pg/ml vs. 7,072 ± 1,339 pg/ml), VEGFA (318.3 ± 37.89 pg/ml vs. 201.5 ± 22.91 pg/ml). The mentioned parameters are associated with smooth muscle contractions, urothelial barrier, transportation and release of transmitters, or bladder compensation. Thus, the presented findings allow to suggest a possible future role of asiatic acid in the prevention of conditions accompanied by DO, such as overactive bladder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.574108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878531PMC
January 2021

Effects of classic antiseizure drugs on seizure activity and anxiety-like behavior in adult zebrafish.

Toxicol Appl Pharmacol 2021 03 30;415:115429. Epub 2021 Jan 30.

Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sklodowska University, Akademicka 19, PL 20-033 Lublin, Poland. Electronic address:

The zebrafish is extensively used as a model organism for studying several disorders of the central nervous system (CNS), including epilepsy. Some antiseizure drugs (ASDs) have been shown to produce discrepant results in larvae and adults zebrafish, therefore, their anticonvulsant efficacy in subsequent stages of the pentylenetetrazole (PTZ)-induced seizures should be more precisely characterized. The purpose of this study was to investigate behavioral effects of five classic ASDs: valproate (VPA), phenytoin (PHT), carbamazepine (CBZ), diazepam (DZP), and phenobarbital (PB) administered intraperitoneally (i.p.) in the PTZ-induced seizure test in adult zebrafish. We determined the time of maximal effect and the dose-response relationship of the studied ASDs. Furthermore, we assessed changes in the locomotor activity and the anxiety-like behavior in the color preference test. Moreover, drug concentrations in zebrafish homogenates were examined. VPA, DZP, and PB significantly increased the seizure latency at three subsequent stages of seizures (SI-SIII). PHT produced the anticonvulsant-like effect at SI and SII, while CBZ was effective at SII and SIII. Only DZP decreased zebrafish locomotor activity. A strong anxiolytic-like effect was observed after administration of PHT and PB. A weak anxiolytic-like effect occurred after treatment with VPA and DZP. The HPLC analysis showed the average concentrations of the studied ASDs in the fish body during the maximum anticonvulsant activity of each drug. Our results confirm the advantages of using zebrafish with the mature CNS over larval models and its utility to investigate some neuropharmacological properties of the tested drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.taap.2021.115429DOI Listing
March 2021

Neuroprotective Effects of Coffee Bioactive Compounds: A Review.

Int J Mol Sci 2020 Dec 24;22(1). Epub 2020 Dec 24.

Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland.

Coffee is one of the most widely consumed beverages worldwide. It is usually identified as a stimulant because of a high content of caffeine. However, caffeine is not the only coffee bioactive component. The coffee beverage is in fact a mixture of a number of bioactive compounds such as polyphenols, especially chlorogenic acids (in green beans) and caffeic acid (in roasted coffee beans), alkaloids (caffeine and trigonelline), and the diterpenes (cafestol and kahweol). Extensive research shows that coffee consumption appears to have beneficial effects on human health. Regular coffee intake may protect from many chronic disorders, including cardiovascular disease, type 2 diabetes, obesity, and some types of cancer. Importantly, coffee consumption seems to be also correlated with a decreased risk of developing some neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and dementia. Regular coffee intake may also reduce the risk of stroke. The mechanism underlying these effects is, however, still poorly understood. This review summarizes the current knowledge on the neuroprotective potential of the main bioactive coffee components, i.e., caffeine, chlorogenic acid, caffeic acid, trigonelline, kahweol, and cafestol. Data from both in vitro and in vivo preclinical experiments, including their potential therapeutic applications, are reviewed and discussed. Epidemiological studies and clinical reports on this matter are also described. Moreover, potential molecular mechanism(s) by which coffee bioactive components may provide neuroprotection are reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22010107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795778PMC
December 2020

The in vitro efficacy of eye drops containing a bacteriophage solution specific for Staphylococcus spp. isolated from dogs with bacterial conjunctivitis.

Ir Vet J 2020 Nov 4;73(1):21. Epub 2020 Nov 4.

SubDepartment of Veterinary Prevention and Avian Diseases, Institute of Biological Bases of Animal Diseases, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland.

Background: The purpose of the study was to evaluate the in vitro antibacterial effect of experimental eye drops with bacteriophages in elimination of Staphylococcus spp. isolated from dogs with bacterial conjunctivitis.. The bacterial material was collected from dogs with independent clinical signs of bacterial conjunctivitis. Staphylococcus spp. were identified by phenotypic and genotypic methods (MALDI-TOF MS mass spectrometry). Antibiotic resistance was determined by the disc-diffusion method. Phage activity (Plaque forming units, PFU) was determined on double-layer agar plates. Phages with lytic titres > 10 PFU were used to prepare eye drops. The stability of the antibacterial titre was evaluated for preparations stored in sealed bottles as well as after opening and reclosing.

Results: The tests confirmed the occurrence of Staphylococcus spp. strains as etiological agents of bacterial conjunctivitis in dogs. A high percentage of strains were resistant to more than three antibiotics. The experimental phage eye drops used in the study exhibited 100% efficacy in vitro against the tested Staphylococcus isolates. Particularly noteworthy is the long duration of activity and constant antibacterial lytic titre of ≥10 PFU/mL of two eye drop solutions, nos. 7 and 12, after the bottle had been opened (21 days) and after hermetically sealed packaging (28 days) at 4-8 °C.

Conclusions: The results represent the first stage of research and require continuation in vivo. If positive effects are obtained in animals, the results can be used in applied research in humans and animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13620-020-00175-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643432PMC
November 2020

IMMUNODIAGNOSIS IN MEMBRANOUS NEPHROPATHY.

Wiad Lek 2020 ;73(9 cz. 1):1861-1866

DEPARTAMENT OF REHABILITATION, CITY HOSPITAL OF TORUN, TORUN, POLAND.

One of the diseases leading to chronic end-stage renal disease is membranous nephropathy (MN). The main cause of this disease is the formation of antibodies to foreign and native antigens. Membranous nephropathy can be conventionally divided into 2 types: primary form (when the primary disease is unknown) and secondary form. Detection of appropriate antibodies is one of the methods to recognize and differentiate primary and secondary forms. A large role in non-invasive diagnosis of MN and differentiation of the primary form from the secondary play antinuclear antibodies (ANA), antibodies against granulocyte cytoplasm (ANCA), antiglomerular basement antibodies (anti-GBM) and phospholipase A2 receptor antibodies (anti-PLA2R). Differentiation matters when choosing a treatment choice. In the primary form, it is immunosuppression, and in the form of secondary treatment, it consists in curing or controlling diseases that can cause symptoms of MN. The aim: Analysis of serological methods helpful in immunodiagnosis of membranous nephropathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2020

DISORDERS OF THE INTESTINAL FLORA AND IT IS EFFECT ON SKELETAL SYSTEM DISEASES.

Wiad Lek 2020 ;73(9 cz. 1):1835-1839

DEPARTMENT OF CONSERVATIVE DENTISTRY AND PEDODONTICS, WROCLAW MEDICAL UNIVERSITY, WROCLAW, POLAND.

The intestinal microflora plays an important role in the proper functioning of human. It is complex, diverse and dynamic ecosystem that constantly strives to maintain homeostasis throughout the body. The process of acquiring intestinal microflora begins immediately after human birth. Elementary factors that determine the modification of the composition of the microflora are age, sex, diet, lifestyle. Determinate individual composition of the microflora. Microorganisms inhabiting the intestine perform various functions, from metabolic, immune to trophic. Early changes in the intestinal microflora are reflected in the state of human health. Recently, many studies have been carried out confirming the hypothesis that the bacterial flora of the gastrointestinal tract affects the normal metabolism of bone tissue, and disorders in its composition can lead to the appearance of bumps in the processes of physiological remodeling of bone tissue and contribute to the formation of many inflammations. Microorganisms that rot in the digestive tract regulate bone metabolism through three mechanisms: the impact on the immune system, the hormonal system and the impact on the absorption of minerals. Disorders in the microflora of the digestive tract can lead to the development of inflammatory bowel diseases, and as a consequence to the accelerated development of osteoporosis or arthrosis of the joints. The aim: To collect available publications confirming the impact of microflora on the skeletal system.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2020

Polyvalent Mechanical Bacterial Lysate Administration Improves the Clinical Course of Grass Pollen-Induced Allergic Rhinitis in Children: A Randomized Controlled Trial.

J Allergy Clin Immunol Pract 2021 01 26;9(1):453-462. Epub 2020 Aug 26.

Department of Applied and Social Pharmacy, Medical University of Lublin, Lublin, Poland.

Background: Recent studies highlight the immunoregulatory potential of bacterial lysates, indicating their potential use in the prevention and treatment of allergic diseases.

Objective: To investigate the clinical efficacy of polyvalent mechanical bacterial lysates (PMBLs) in children with grass pollen-induced allergic rhinitis.

Methods: Seventy children with seasonal allergic rhinitis were enrolled to this study and were randomly assigned to the PMBL and placebo groups. Severity of seasonal allergic rhinitis symptoms was assessed by the total nasal symptom score, total ocular symptom score, and visual analogue scale. During 3 visits, peak nasal inspiratory flow was measured, and nasal smears for the presence of eosinophils and nasal lavage fluids for the presence of allergen-specific IgE against timothy grass pollen allergens were sampled.

Results: A statistically significant decrease in total nasal symptom score (P = .001), total ocular symptom score (P = .04), and visual analogue scale score for nasal and eye symptoms (P < .001 and P < .001, respectively) and an increase in peak nasal inspiratory flow (P = .04) were observed in the PMBL group versus the placebo group. During the grass pollen season, an increase and then a decrease in the number of eosinophils in nasal smears was observed in both groups; however, the number of eosinophils was significantly lower in the PMBL group versus the placebo group. No significant changes in allergen-specific IgE concentrations were observed in the PMBL group, whereas in the placebo group a statistically significant increase in allergen-specific IgE concentration was observed.

Conclusions: Sublingual administration of PMBLs during the grass pollen season offers significant efficacy in alleviating seasonal allergic rhinitis symptoms in children sensitized to grass pollen allergens. PMBLs probably affect mucosal immunity, weakening the response of T2 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.08.025DOI Listing
January 2021

Imipramine Influences Body Distribution of Supplemental Zinc Which May Enhance Antidepressant Action.

Nutrients 2020 Aug 20;12(9). Epub 2020 Aug 20.

Department of Neurobiology, Polish Academy of Sciences, Maj Institute of Pharmacology, 12 Smętna Street, 31-343 Kraków, Poland.

Zinc (Zn) was found to enhance the antidepressant efficacy of imipramine (IMI) in human depression and animal tests/models of depression. However, the underlying mechanism for this effect remains unknown. We measured the effect of intragastric () combined administration of IMI (60 mg/kg) and Zn (40 mg Zn/kg) in the forced swim test (FST) in mice. The effect of Zn + IMI on serum, brain, and intestinal Zn concentrations; Zn transporter (ZnT, ZIP) protein levels in the intestine and ZnT in the brain; including BDNF (brain-derived neurotrophic factor) and CREB (cAMP response element-binding protein) protein levels in the brain were evaluated. Finally, the effect of IMI on Zn permeability was measured in vitro in colon epithelial Caco-2 cells. The co-administration of IMI and Zn induced antidepressant-like activity in the FST in mice compared to controls and Zn or IMI given alone. This effect correlated with increased BDNF and the ratio of pCREB/CREB protein levels in the prefrontal cortex (PFC) compared to the control group. Zn + IMI co-treatment increased Zn concentrations in the serum and brain compared to the control group. However, in serum, co-administration of IMI and Zn decreased Zn concentration compared to Zn alone treatment. Also, there was a reduction in the Zn-induced enhancement of ZnT1 protein level in the small intestine. Zn + IMI also induced an increase in the ZnT4 protein level in the PFC compared to the control group and normalized the Zn-induced decrease in the ZnT1 protein level in the hippocampus (Hp). The in vitro studies revealed enhanced Zn permeability (observed as the increased transfer of Zn through the intestinal cell membrane) after IMI treatment. Our data indicate that IMI enhances Zn transfer through the intestinal tract and influences the redistribution of Zn between the blood and brain. These mechanisms might explain the enhanced antidepressant efficacy of combined IMI/Zn treatment observed in the FST in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12092529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551732PMC
August 2020

Imipramine Influences Body Distribution of Supplemental Zinc Which May Enhance Antidepressant Action.

Nutrients 2020 Aug 20;12(9). Epub 2020 Aug 20.

Department of Neurobiology, Polish Academy of Sciences, Maj Institute of Pharmacology, 12 Smętna Street, 31-343 Kraków, Poland.

Zinc (Zn) was found to enhance the antidepressant efficacy of imipramine (IMI) in human depression and animal tests/models of depression. However, the underlying mechanism for this effect remains unknown. We measured the effect of intragastric () combined administration of IMI (60 mg/kg) and Zn (40 mg Zn/kg) in the forced swim test (FST) in mice. The effect of Zn + IMI on serum, brain, and intestinal Zn concentrations; Zn transporter (ZnT, ZIP) protein levels in the intestine and ZnT in the brain; including BDNF (brain-derived neurotrophic factor) and CREB (cAMP response element-binding protein) protein levels in the brain were evaluated. Finally, the effect of IMI on Zn permeability was measured in vitro in colon epithelial Caco-2 cells. The co-administration of IMI and Zn induced antidepressant-like activity in the FST in mice compared to controls and Zn or IMI given alone. This effect correlated with increased BDNF and the ratio of pCREB/CREB protein levels in the prefrontal cortex (PFC) compared to the control group. Zn + IMI co-treatment increased Zn concentrations in the serum and brain compared to the control group. However, in serum, co-administration of IMI and Zn decreased Zn concentration compared to Zn alone treatment. Also, there was a reduction in the Zn-induced enhancement of ZnT1 protein level in the small intestine. Zn + IMI also induced an increase in the ZnT4 protein level in the PFC compared to the control group and normalized the Zn-induced decrease in the ZnT1 protein level in the hippocampus (Hp). The in vitro studies revealed enhanced Zn permeability (observed as the increased transfer of Zn through the intestinal cell membrane) after IMI treatment. Our data indicate that IMI enhances Zn transfer through the intestinal tract and influences the redistribution of Zn between the blood and brain. These mechanisms might explain the enhanced antidepressant efficacy of combined IMI/Zn treatment observed in the FST in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12092529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551732PMC
August 2020

Mineral and trace element composition of the roe and muscle tissue of farmed rainbow trout (Oncorhynchus mykiss) with respect to nutrient requirements: Elements in rainbow trout products.

J Trace Elem Med Biol 2020 Dec 9;62:126619. Epub 2020 Jul 9.

Institute of Quality Assessment and Processing of Animal Products, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland.

Background: Due to excellent nutritional properties of fish and fish products, dietitians recommend their larger share in the diet, for both the prevention and treatment of diet-related diseases. In this context particular attention should be given to fish eggs (roe). The aim of the study was to compare the content of selected minerals and trace elements in the roe and muscle tissue of aquaculture-reared rainbow trout. Moreover, the extent to which an edible portion of 100 g of fish product (roe or fillet) satisfies the requirements for these elements in adult consumers (women and men) and children was determined.

Methods: The research material was represented by 20 farmed rainbow trout females (Oncorhynchus mykiss). In muscle tissue and roe the proximate composition, energy value, and nutritional quality index were examined. Concentrations of K, Na, Ca, Mg, Zn, Fe, Mn and Cu were determined by flame atomic absorption spectrometry analysis. The levels of minerals and trace elements in fish products were used to calculate the percentages of the recommended dietary reference values for adults and children in portion of 100 g.

Results: The roe had higher content of 7 elements including, Zn (29.40 ± 1.38, 27.74-30.91 mg/kg), Mn (1.66 ± 0.08, 1.55-1.73 mg/kg), Fe (11.17 ± 0.35, 10.75-11.60 mg/kg), Cu (1.24 ± 0.04, 1.21-1.30 mg/kg), Ca (546.90 ± 23.68, 522.02-578.96 mg/kg), Mg (546.97 ± 23.68, 522.02-578.96 mg/kg), Na (403.61 ± 5.53, 397.29-407.57 mg/kg) compared to muscle tissue, respectively, Zn (2.73 ± 0.97, 0.94-3.77 mg/kg, Mn (0.22 ± 0.10, 0.14-0.46 mg/kg), Fe (2.19 ± 1.44, 1.02-5.50 mg/kg), Cu (0.24 ± 0.06, 0.17-0.36 mg/kg), Ca (164.07 ± 71.72, 93.24-306.32 mg/kg), Mg (240.00 ± 73.37, 127.92-316.41 mg/kg), Na (273.37 ± 99.65, 183.93-524.41 mg/kg). In turn, the muscle tissue contained 3 times as much K (5159.87 ± 974.70, 4004.63-6343.91 mg/kg) as the roe (1713.65 ± 58.68, 1643.97-1764.14 mg/kg). The roe covered the recommended nutrition standards (population reference intake, PRI and adequate intake, AI) to a greater extent than the fillet for all analysed trace elements and minerals except K. For children, the contribution of roe to the reference intake of such elements as Mg, Zn, Fe, Mn and Cu was particularly high. Therefore the roe should be considered as a source of Mg for all consumer groups, and as high in Zn for women and children. The suggested portion of fillet and roe provided only 2-3 % of the daily requirement for Na.

Conclusions: Despite the differences found, both roe and fillet from rainbow trout are a good source of analysed elements. The results indicate the need to continue research in order to determine the influence of other factors on the content of minerals and trace elements in roe and the possibility of using gonads to enrich other food products with elements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtemb.2020.126619DOI Listing
December 2020

Stimulation of atypical cannabinoid receptor GPR55 abolishes the symptoms of detrusor overactivity in spontaneously hypertensive rats.

Eur J Pharm Sci 2020 Jul 29;150:105329. Epub 2020 Apr 29.

Chair and Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland.

Overactive bladder is a troublesome disease that affects 15% of the population in developed countries. Since pharmacotherapy of this condition is frequently associated with side effects, the better tolerated drugs are being searched for. The main objective of our study was to check whether activation of the atypical cannabinoid receptor GPR55 would normalize the changes in cystometric, cardiovascular and biochemical parameters in the hypertensive female Wistar-Kyoto rats presenting the symptoms of overactive bladder accompanied by inflammation and oxidative damage in the urinary tracts. A 14-day intra-arterial administration of O-1602 (0.25 mg/kg/day), a potent agonist of GRP55 receptors, was able to abolish the signs of detrusor overactivity, inflammation and oxidative damage in the urinary bladder of the spontaneously hypertensive animals. Moreover, it increased their heart rate, reduced the mean blood pressure, and normalized the levels of several proteins that play a significant role in the proper functioning of the urinary bladder (i.e., calcitonin gene related peptide, organic cation transporter 3, extracellular signal-regulated kinase 1/2, vesicular acetylcholine transporter, RhoA). Based on the outcomes of our experiments, the atypical cannabinoid receptor GPR55 has emerged as a potential drug target for the treatment of overactive bladder in female subjects. It could be particularly attractive in the cases in which this condition is accompanied with elevated blood pressure, though further studies on this subject are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2020.105329DOI Listing
July 2020

Influence of the endocannabinoid system on the antidepressant activity of bupropion and moclobemide in the behavioural tests in mice.

Pharmacol Rep 2020 Dec 27;72(6):1562-1572. Epub 2020 Mar 27.

Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland.

Background: Though there are several classes of antidepressant drugs available on the pharmaceutical market, depression that affects globally over 320 million people is still undertreated. Scientists have made attempts to develop novel therapeutical strategies to maximize effectiveness of therapy and minimize undesired reactions. One of the ideas is use of either dual-action agents or combined administration of two substances that affect diverse neurotransmissions. Thus, we investigated whether the selected CB receptor ligands (oleamide, AM251, JWH133, and AM630) can have an impact on the activity of bupropion and moclobemide. Bupropion belongs to the dual acting drugs, whereas moclobemide is an inhibitor of monoamine oxidase.

Methods: The mice forced swim test and the tail suspension test were applied in order to determine the potential antidepressant-like activity, whereas the HPLC method was used in order to assess the brain concentrations of the tested antidepressants.

Results: An intraperitoneal injection of sub-effective doses of oleamide (5 mg/kg), AM251 (0.25 mg/kg), and AM630 (0.25 mg/kg) increased activity of bupropion (10 mg/kg) in both behavioural tests. Effects of moclobemide (1.5 mg/kg) were potentiated only by AM251. These results were not influenced by the hypo- or hyperlocomotion of animals.

Conclusion: The outcomes of the present study revealed that particularly activation or inhibition of the CB receptor function may augment the antidepressant activity of bupropion, whereas only inhibition of the CB receptor function manages to increase activity of moclobemide. Most probably, an interplay between CB receptor ligands and bupropion or moclobemide takes place at the cellular level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43440-020-00088-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704509PMC
December 2020

A Novel Alternative in the Treatment of Detrusor Overactivity? In Vivo Activity of O-1602, the Newly Synthesized Agonist of GPR55 and GPR18 Cannabinoid Receptors.

Molecules 2020 Mar 18;25(6). Epub 2020 Mar 18.

Chair and Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, 1 Chodźki St., PL-20093 Lublin, Poland.

The aim of the research was to assess the impact of O-1602-novel GPR55 and GPR18 agonist-in the rat model of detrusor overactivity (DO). Additionally, its effect on the level of specific biomarkers was examined. To stimulate DO, 0.75% retinyl acetate (RA) was administered to female rats' bladders. O-1602, at a single dose of 0.25 mg/kg, was injected intra-arterially during conscious cystometry. Furthermore, heart rate, blood pressure, and urine production were monitored for 24 h, and the impact of O-1602 on the levels of specific biomarkers was evaluated. An exposure of the urothelium to RA changed cystometric parameters and enhanced the biomarker levels. O-1602 did not affect any of the examined cystometric parameters or levels of biomarkers in control rats. However, the O-1602 injection into animals with RA-induced DO ameliorated the symptoms of DO and caused a reversal in the described changes in the concentration of CGRP, OCT, BDNF, and NGF to the levels observed in the control, while the values of ERK1/2 and VAChT were significantly lowered compared with the RA-induced DO group, but were still statistically higher than in the control. O-1602 can improve DO, and may serve as a promising novel substance for the pharmacotherapy of bladder diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25061384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144400PMC
March 2020

Duloxetine reverses the symptoms of overactive bladder co-existing with depression via the central pathways.

Pharmacol Biochem Behav 2020 02 31;189:172842. Epub 2019 Dec 31.

Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Lublin, Poland.

Though the association between overactive bladder (OAB) and depression was noticed years ago, the pharmaceutical market does not offer one universal drug that would cure both conditions at the same time. The main goal of our present experiments was to determine whether a 14-day administration of solifenacin (0.03 mg/kg/day), mirabegron (1 mg/kg/day), or duloxetine (1 mg/kg/day) would reverse detrusor overactivity and depression-like signs in female Wistar rats subjected to corticosterone treatment. Surgical procedures, cystometric studies, biochemical analyses, and the forced swim test were performed according to published literature. After 14 days of exposure to corticosterone (20 mg/kg/day, subcutaneously), the tested animals presented symptoms of depression, detrusor overactivity, inflammation, and disturbances in neurotrophic factors. The obtained results demonstrated that solifenacin and mirabegron act mainly via peripheral pathways in OAB, whereas the central pathways are responsible for the effects of duloxetine. 72 h after discontinuation of duloxetine treatment, positive changes in the corticosterone-induced depression, detrusor overactivity, and inflammation were observed. Duloxetine seems to have a potential to become a new treatment option for patients with OAB co-existing with depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pbb.2019.172842DOI Listing
February 2020

Influence of the CB and CB cannabinoid receptor ligands on the activity of atypical antidepressant drugs in the behavioural tests in mice.

Pharmacol Biochem Behav 2020 01 27;188:172833. Epub 2019 Nov 27.

Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland. Electronic address:

Available data support the notion that cannabinoids, whose therapeutic value is limited due to severe adverse reactions, could be beneficial as adjunctive agents in the management of mood disorders. Polytherapy, which is superior to monotherapy in the terms of effectiveness, usually requires lower doses of the individual components. Therefore, the main objective of our study was to determine whether administration of cannabinoid (CB) receptor ligands would enhance the antidepressant activity of atypical antidepressant drugs, i.e. agomelatine and tianeptine. To evaluate the antidepressant-like potential of the tested combinations, the mouse forced swim test (FST) and the tail suspension test (TST) were used. The HPLC method was applied to assess the brain levels of agomelatine and tianeptine. Both behavioural tests demonstrated that per se an ineffective intraperitoneal dose of oleamide (CB receptor agonist, 5 mg/kg) potentiated the anti-immobility activity of tianeptine (15 mg/kg), whereas AM251 (CB receptor inverse agonist/antagonist, 0.25 mg/kg) enhanced the antidepressant effects of tianeptine and agomelatine (20 mg/kg). Intraperitoneal co-administration of per se inactive doses of AM630 (CB receptor inverse agonist/antagonist) and agomelatine or tianeptine significantly reduced the immobility time of animals only in the FST. CB receptor ligands did not affect the brain levels of the tested atypical antidepressants. In summary, the outcomes of the present study showed that activation and inhibition of CB receptors as well as inhibition of CB receptors may increase the antidepressant activity of tianeptine, whereas only inhibition of CB and CB receptors has a potential to augment the antidepressant activity of agomelatine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pbb.2019.172833DOI Listing
January 2020

Ligands of the CB2 cannabinoid receptors augment activity of the conventional antidepressant drugs in the behavioural tests in mice.

Behav Brain Res 2020 01 15;378:112297. Epub 2019 Oct 15.

Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland. Electronic address:

Although a lot of information can be found on the specific dual role of the endocannabinoid system in the emotional-related responses, little is known whether stimulation or inhibition of the cannabinoid (CB) receptors may affect the activity of the frequently prescribed antidepressant drugs. Our interests have been particularly focused on the potential influence of the CB receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB receptors. Therefore, we evaluated the potential interaction between the CB receptor ligands (i.e., JWH133 - CB receptor agonist and AM630 - CB receptor inverse agonist) and several common antidepressant drugs that influence the monoaminergic system (i.e., imipramine, escitalopram, reboxetine). In order to assess the antidepressant-like effects we used two widely recognized behavioural tests, the mouse forced swim test (FST) and the tail suspension test (TST). Brain concentrations of the tested antidepressants were evaluated by the HPLC method. Intraperitoneal co-administration of per se ineffective doses of JWH133 (0.25 mg/kg) or AM630 (0.25 mg/kg) with imipramine (15 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg) significantly shortened the immobility time of mice in the FST and the TST, whereas it did not disturb their spontaneous locomotor activity. Furthermore, the brain levels of antidepressants were not changed. Summarizing, the results of the present study revealed that both activation and inhibition of the CB receptor function have a potential to strengthen the antidepressant activity of drugs targeting the monoaminergic system. Most probably, the described interaction has a pharmacodynamic background.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2019.112297DOI Listing
January 2020

Agomelatine and tianeptine antidepressant activity in mice behavioral despair tests is enhanced by DMPX, a selective adenosine A receptor antagonist, but not DPCPX, a selective adenosine A receptor antagonist.

Pharmacol Rep 2019 Aug 16;71(4):676-681. Epub 2019 Mar 16.

Department of Applied Pharmacy, Medical University of Lublin, Lublin, Poland. Electronic address:

Background: Adenosine, an endogenous nucleoside, modulates the release of monoamines, e.g., noradrenaline, serotonin, and dopamine in the brain. Both nonselective and selective stimulation of adenosine receptors produce symptoms of depression in some animal models. Therefore, the main objective of our study was to assess the influence of a selective adenosine A receptor antagonist (DPCPX) and a selective adenosine A receptor antagonist (DMPX) on the activity of agomelatine and tianeptine.

Methods: The forced swim test (FST) and tail suspension test (TST) were performed to assess the effects of DPCPX and DMPX on the antidepressant-like activity of agomelatine and tianeptine. Drug serum and brain levels were analyzed using HPLC.

Results: Co-administration of agomelatine (20 mg/kg) or tianeptine (15 mg/kg) with DMPX (3 mg/kg), but not with DPCPX (1 mg/kg), significantly reduced the immobility time both in the FST and TST in mice. These effects were not associated with an enhancement in animals' spontaneous locomotor activity. The observed changes in the mouse behavior after concomitant injection of DMPX and the tested antidepressant agents were associated with elevated brain concentration of agomelatine and tianeptine.

Conclusion: Our study shows a synergistic action of the selective A receptor antagonist and the studied antidepressant drugs, and a lack of such interaction in the case of the selective A receptor antagonist. The interaction between DMPX and agomelatine/tianeptine at least partly occurs in the pharmacokinetic phase. A combination of a selective A receptor antagonist and an antidepressant may be a new strategy for treating depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pharep.2019.03.007DOI Listing
August 2019

Influence of the CB cannabinoid receptors on the activity of the monoaminergic system in the behavioural tests in mice.

Brain Res Bull 2019 08 31;150:179-185. Epub 2019 May 31.

Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland. Electronic address:

Antidepressants that target the monoaminergic system are prescribed most frequently in the psychiatric practice. However, not all patients benefit from their use. It is generally known that co-administration of agents aiming distinct targets may increase the therapeutic effect and at the same time permit dose reduction. A number of studies have suggested a CB receptor-mediated interplay between the endocannabinoid system and the monoaminergic signalling in the brain. Therefore, we wanted to determine whether the CB receptor ligands (oleamide and AM251) affect the activity of the common antidepressant drugs that influence the monoaminergic system. In order to determine the antidepressant-like activity, the forced swim test and the tail suspension test in mice were used. Additionally, brain concentrations of the tested antidepressants were evaluated by the HPLC method. Concurrent intraperitoneal administration of per se inactive doses of oleamide (5 mg/kg) or AM251 (0.25 mg/kg) and imipramine (15 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg) reduced the immobility time of animals in the forced swim test and the tail suspension test. The observed effect was not associated with hyperlocomotion of animals. Summarizing, the outcomes of the present study demonstrated that modulation (i.e., activation or inhibition) of the CB receptor function potentiates the antidepressant activity of common drugs that influence the monoaminergic (serotonergic and noradrenergic) system. This effect is most probably predominantly pharmacodynamic in nature instead of pharmacokinetic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainresbull.2019.05.021DOI Listing
August 2019

The influence of nebivolol on the activity of BRL 37344 - the β3-adrenergic receptor agonist, in the animal model of detrusor overactivity.

Neurourol Urodyn 2019 06 1;38(5):1229-1240. Epub 2019 Apr 1.

Chair and Department of Applied Pharmacy, Medical University of Lublin, Lublin, Poland.

Aims: The cardiotoxic effects of antimuscarinics constitute a significant restriction in their application in elderly people. Overactive bladder syndrome pharmacotherapy using compounds with cardioprotective properties would seem an ideal solution. The main goal of the study was to assess the impacts of nebivolol (NEB) on the activity of BRL 37344 - β3-adrenergic receptor (β3AR) agonist, in the animal model of detrusor overactivity. As both these substances can impact on the cardiovascular system, their effect on the parameters of this system and diuresis was also examined.

Methods: Retinyl acetate (RA; 0.75%) solution was used to induce detrusor overactivity in female Wistar rats. BRL and/or NEB were administered intra-arterially during cystometry in a single dose (2.5 or 5, 0.05 or 0.1 mg/kg, respectively). In addition, a 24 hours measurement of heart rate, blood pressure, and urine production was carried out.

Results: NEB (0.05 mg/kg) and BRL (2.5 mg/kg) monotherapy proved to have no influence on the cystometric parameters of animals with RA-induced detrusor overactivity. NEB at 0.1 mg/kg resulted in a drop in the detrusor overactivity index, similarly to BRL at 5 mg/kg. Coadministration of NEB and BRL, both at ineffective doses, decreased the detrusor overactivity index and ameliorated the nonvoiding contractions. β3AR stimulation proved to induce tachycardia and hypertension. NEB at 0.05 mg/kg proved to ameliorate detrusor overactivity and have preventive properties against adverse cardiovascular effects of the β3AR agonist.

Conclusions: The combined application of the β3AR agonist and NEB may improve detrusor overactivity without affecting the heart rate, blood pressure, and urine production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nau.23993DOI Listing
June 2019

Intravesical administration of blebbistatin prevents cyclophosphamide-induced toxicity of the urinary bladder in female Wistar rats.

Neurourol Urodyn 2019 04 14;38(4):1044-1052. Epub 2019 Mar 14.

Chair and Department of Applied Pharmacy, Medical University of Lublin, Lublin, Poland.

Aims: The main goal of our study was to investigate whether blebbistatin would prevent the cyclophosphamide (CYP)-induced changes in cystometric and inflammatory parameters indicating the development of bladder inflammation and bladder overactivity. As the nature of CYP-induced urotoxicity is inflammatory, we assume that agents presenting an anti-inflammatory potential, such as blebbistatin, are worth special attention.

Materials And Methods: The experiments were carried out in female Wistar rats. Surgical procedures, cystometric investigations, measurements of bladder edema and urothelium thickness as well as biochemical analyses were performed according to the published literature.

Results: As expected, an acute administration of CYP (200 mg/kg, intraperitoneally) induced changes in the cystometric parameters and the levels of the tested biomarkers (ie, interleukin 1-β, interleukin 6, interleukin 10, tumor necrosis factor-α, nerve growth factor, brain-derived neurotrophic factor, heparin-binding epidermal growth factor-like growth factor, insulin-like growth factor-binding protein 3, C-X-C motif chemokine 10, orosomucoid-1, Tamm-Horsfall protein, hemopexin, and occludin), indicating the development of bladder overactivity and bladder inflammation, respectively. These changes were accompanied by bladder edema and increased urothelium thickness. Intravesical infusion of blebbistatin for 7 days (125 nmol/day) prevented all symptoms of the CYP-induced urotoxicity.

Conclusions: Blebbistatin might be a promising novel agent for the treatment of bladder dysfunctions, like CYP-induced hemorrhage cystitis or bladder overactivity, since it diminished the increased urinary bladder levels of proinflammatory markers and normalized the concentrations of the anti-inflammatory ones. This effect was accompanied by amelioration of bladder edema and permeability, and normalization of both urothelium thickness and values of the cystometric parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nau.23973DOI Listing
April 2019
-->