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1.
Int J Mol Sci ; 25(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38396896

RESUMO

Late cardiotoxicity is a formidable challenge in anthracycline-based anticancer treatments. Previous research hypothesized that co-administration of carvedilol (CVD) and dexrazoxane (DEX) might provide superior protection against doxorubicin (DOX)-induced cardiotoxicity compared to DEX alone. However, the anticipated benefits were not substantiated by the findings. This study focuses on investigating the impact of CVD on myocardial redox system parameters in rats treated with DOX + DEX, examining its influence on overall toxicity and iron metabolism. Additionally, considering the previously observed DOX-induced ascites, a seldom-discussed condition, the study explores the potential involvement of the liver in ascites development. Compounds were administered weekly for ten weeks, with a specific emphasis on comparing parameter changes between DOX + DEX + CVD and DOX + DEX groups. Evaluation included alterations in body weight, feed and water consumption, and analysis of NADPH2, NADP+, NADPH2/NADP+, lipid peroxidation, oxidized DNA, and mRNA for superoxide dismutase 2 and catalase expressions in cardiac muscle. The iron management panel included markers for iron, transferrin, and ferritin. Liver abnormalities were assessed through histological examinations, aspartate transaminase, alanine transaminase, and serum albumin level measurements. During weeks 11 and 21, reduced NADPH2 levels were observed in almost all examined groups. Co-administration of DEX and CVD negatively affected transferrin levels in DOX-treated rats but did not influence body weight changes. Ascites predominantly resulted from cardiac muscle dysfunction rather than liver-related effects. The study's findings, exploring the impact of DEX and CVD on DOX-induced cardiotoxicity, indicate a lack of scientific justification for advocating the combined use of these drugs at histological, biochemical, and molecular levels.


Assuntos
Ascite , Cardiotoxicidade , Ratos , Animais , Carvedilol/farmacologia , NADP/metabolismo , Cardiotoxicidade/metabolismo , Ascite/patologia , Doxorrubicina/uso terapêutico , Miocárdio/metabolismo , Antibióticos Antineoplásicos/uso terapêutico , Ferro/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Transferrina/metabolismo , Peso Corporal
2.
Int J Mol Sci ; 24(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37373350

RESUMO

The anticancer efficacy of doxorubicin (DOX) is dose-limited because of cardiomyopathy, the most significant adverse effect. Initially, cardiotoxicity develops clinically silently, but it eventually appears as dilated cardiomyopathy with a very poor prognosis. Dexrazoxane (DEX) is the only FDA-approved drug to prevent the development of anthracycline cardiomyopathy, but its efficacy is insufficient. Carvedilol (CVD) is another product being tested in clinical trials for the same indication. This study's objective was to evaluate anthracycline cardiotoxicity in rats treated with CVD in combination with DEX. The studies were conducted using male Wistar rats receiving DOX (1.6 mg/kg b.w. i.p., cumulative dose: 16 mg/kg b.w.), DOX and DEX (25 mg/kg b.w. i.p.), DOX and CVD (1 mg/kg b.w. i.p.), or a combination (DOX + DEX + CVD) for 10 weeks. Afterward, in the 11th and 21st weeks of the study, echocardiography (ECHO) was performed, and the tissues were collected. The addition of CVD to DEX as a cardioprotective factor against DOX had no favorable advantages in terms of functional (ECHO), morphological (microscopic evaluation), and biochemical alterations (cardiac troponin I and brain natriuretic peptide levels), as well as systemic toxicity (mortality and presence of ascites). Moreover, alterations caused by DOX were abolished at the tissue level by DEX; however, when CVD was added, the persistence of DOX-induced unfavorable alterations was observed. The addition of CVD normalized the aberrant expression of the vast majority of indicated genes in the DOX + DEX group. Overall, the results indicate that there is no justification to use a simultaneous treatment of DEX and CVD in DOX-induced cardiotoxicity.


Assuntos
Cardiomiopatias , Dexrazoxano , Masculino , Ratos , Animais , Dexrazoxano/farmacologia , Dexrazoxano/uso terapêutico , Antraciclinas/efeitos adversos , Carvedilol/farmacologia , Carvedilol/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Ratos Wistar , Antibióticos Antineoplásicos/toxicidade , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/prevenção & controle , Cardiomiopatias/tratamento farmacológico , Doxorrubicina/farmacologia , Inibidores da Topoisomerase II/uso terapêutico
3.
Antioxidants (Basel) ; 12(6)2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37371983

RESUMO

As new sources of proteins, edible insects may be excellent additives in a new generation of environmentally friendly food products that are nutritionally valuable, safe, sustainable, and are needed in today's world. The aim of this study was to determine the effect of the application of cricket flour on extruded wheat-corn-based snack pellets' basic composition, fatty acids profile, nutritional value, antioxidant activity and selected physicochemical properties. Results showed that the application of cricket flour had a significant impact on the composition and properties of snack pellets based on wheat-corn blends. In newly developed products, the enhanced level of protein and almost triple increase in crude fiber was found as an insect flour supplementation reached 30% level in the recipe. The level of cricket flour and the applied processing conditions (various moisture contents and screw speeds) significantly affect the water absorption and water solubility index and texture and color profile. Results revealed that cricket flour application significantly increased the total polyphenols content in the assessed samples in comparison to plain wheat-corn bases. Antioxidant activity was also noted to be elevated with increasing cricket flour content. These new types of snack pellets with cricket flour addition may be interesting products with high nutritional value and pro-health properties.

4.
Clin Exp Pharmacol Physiol ; 50(8): 621-633, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37194348

RESUMO

Mephedrone is a representative of synthetic cathinones that is known from its rewarding and psychostimulant effects. It exerts behavioural sensitization after repeated and then interrupted administration. In our study, we investigated a role of the L-arginine-NO-cGMP-dependent signalling in the expression of sensitization to hyperlocomotion evoked by mephedrone. The study was carried out in male albino Swiss mice. The tested mice received mephedrone (2.5 mg/kg) for 5 consecutive days and on the 20th day of the experiment (the 'challenge' day) animals received both mephedrone (2.5 mg/kg) and a given substance that affects the L-arginine-NO-cGMP signalling, that is, L-arginine hydrochloride (125 or 250 mg/kg), 7-nitroindazole (10 or 20 mg/kg), L-NAME (25 or 50 mg/kg) or methylene blue (5 or 10 mg/kg). We observed that 7-nitroindazole, L-NAME and methylene blue inhibited the expression of sensitization to the mephedrone-induced hyperlocomotion. Moreover, we demonstrated that the mephedrone-induced sensitization is accompanied by lowered levels of D1 receptors and NR2B subunits in the hippocampus, whereas a concurrent administration of L-arginine hydrochloride, 7-nitroindazole and L-NAME with the mephedrone challenge dose reversed these effects. Methylene blue only reversed the mephedrone-induced effects on hippocampal levels of the NR2B subunit. Our study confirms that the L-arginine-NO-cGMP pathway contributes to mechanisms underlying the expression of sensitization to the mephedrone-evoked hyperlocomotion.


Assuntos
Azul de Metileno , Óxido Nítrico , Camundongos , Masculino , Animais , NG-Nitroarginina Metil Éster/farmacologia , Azul de Metileno/farmacologia , Óxido Nítrico/metabolismo , Arginina/farmacologia , Locomoção , GMP Cíclico/metabolismo
5.
Molecules ; 28(4)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36838822

RESUMO

The purpose of this study was to determine the effect of the addition of fresh kale and processing conditions on extruded pellet antioxidant activity and selected physicochemical properties. The results of the applied DPPH, FRAP, and TPC methods indicated that, for both 60 and 100 rpm screw speeds, snack pellet antioxidant activity and phenolic content were strongly linked to the fresh kale content, and these properties increased with the addition of this plant. The amount of fresh kale and the applied processing variables (extruder screw speed and the moisture content of the raw material blends) were also found to significantly affect the water absorption index, water solubility index, fat absorption index, fatty acid profile, and basic chemical composition of the obtained extrudates. The sample with the highest phenolic content (72.8 µg GAE/g d.w.), the most advantageous chemical composition (protein, ash, fat, carbohydrates, and fiber content), and high antioxidant properties was produced at a fresh kale content of 30%, a 36% moisture content, and a 100 rpm screw speed. The following phenolic acids were identified in this sample: protocatechuic, 4-OH-benzoic, vanillic, syringic, salicylic, caffeic, coumaric, ferulic, and sinapic. Sinapic acid was the prevailing phenolic acid.


Assuntos
Brassica , Brassica/química , Antioxidantes/análise , Lanches , Fenóis/análise , Água
6.
Materials (Basel) ; 15(14)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35888526

RESUMO

The impact of the amount of durum wheat bran additive used on the selected structural, mechanical, and spectroscopic properties of thermoplastic starch moldings was examined in this study. Bran was added to corn starch from 10 to 60% by weight in the blends. Four temperature settings were used for the high-pressure injection: 120, 140, 160, and 180 °C. The highest value of elongation at break (8.53%) was observed for moldings containing 60% bran. Moreover, for these moldings, the tensile strength and flexural strength were lower (appropriately 3.43 MPa and 27.14 MPa). The highest deformation at break (1.56%) were obtained for samples with 60% bran and injection molded at 180 °C. We saw that higher bran content (50 and 60%) and a higher injection molding temperature (160 °C and 180 °C) significantly changed the color of the samples. The most significant changes in the FTIR spectra were observed at 3292 and 1644 cm-1 and in the region of 1460-1240 cm-1. Moreover, notable changes were observed in the intensity ratio of bands at 1015 and 955 cm-1. The changes observed correspond well with the amount of additive used and with the injection temperature applied; thus it may be considered as a marker of interactions affecting plasticization of the material obtained.

7.
Metabolites ; 12(7)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35888708

RESUMO

The main goal of this study was to determine the antidepressant-like potential of the co-administration of sodium selenite (Se) and the selective adenosine A1 and A2A antagonists DPCPX and istradefylline (IST), respectively, in mice despair tests. Biochemical studies were performed to elucidate the action mechanisms of the investigated treatment strategies. The results confirmed that, when administered by itself, Se exerts an antidepressant-like effect in the FST and TST and that this activity is dose-dependent. Further experiments demonstrated that Se (0.25 mg/kg) significantly enhanced the activity of mice in both tests when co-administered with DPCPX (1 mg/kg) and IST (0.5 mg/kg) at doses which would be ineffective if administered individually. Our research revealed that neither DPCPX, IST, nor Se or combinations of the tested substances induced significant changes in the brain-derived neurotrophic factor (BDNF) levels in mice serum vs. the NaCl-treated group. However, we observed a decrease in the mRNA level of antioxidant defense enzymes. Molecular studies also showed changes in the expression of the Slc6a15, Comt, and Adora1 genes, particularly after exposure to the combination of Se and DPCPX, which indicates a beneficial effect and may help to explain the key mechanism of the antidepressant effect. The combination of Se with substances attenuating adenosine neurotransmission may become a new therapeutic strategy for patients with depression.

8.
Int J Mol Sci ; 23(12)2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35743150

RESUMO

Copper is an essential element to brain cells as it is a cofactor and a structural component of various enzymes involved in energy metabolism pathways. Accumulating evidence points to the pivotal role of copper deficiency in neurodegeneration resulting from impaired copper homeostasis. Despite the indisputable role of copper in mitochondrial respiration, its homeostasis regulation in the brain tissue remains unclear. The assessment of changes in the expression of genes encoding key pathways of energy metabolism can greatly benefit further studies exploring copper's role in neurodegeneration. Using a rat model, we investigate whether the replacement of the inorganic form of copper with metallic nanoparticles containing copper or complete deprivation of copper from the diet have an impact on the expression of genes involved in energy metabolism in the prefrontal cortex of the rats' brain. Herein, we indicate that removing inorganic copper from the normal standard diet or the replacement with copper nanoparticles can lead to programmed energy metabolism changes. It can be recognized that some of these changes indicate an increased demand for NADH in the prefrontal cortex of the rat's brain, probably as a result of adaptation effect.


Assuntos
Cobre , NAD , Animais , Encéfalo/metabolismo , Cobre/metabolismo , Expressão Gênica , NAD/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos
9.
Ann Agric Environ Med ; 29(1): 143-148, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35352918

RESUMO

INTRODUCTION: Clinical manifestation of organophosphates toxicity may be differentiate and include cholinergic toxidrome, intermediate syndrome, OP-induced delayed polyneuropathy to chronic OP-induced neuropsychiatric disorder (OPIDN). Patients symptoms, along with decrease in cholinesterase serum level, determines the possible diagnosis of organophosphate poisoning. OBJECTIVE: The aim of the study was to present the clinical manifestation and cholinesterase level changes in intoxication with organophosphorus compounds in patients. MATERIAL AND METHODS: A data base was created by analysis of the hospital documents of 34 patients hospitalized due to organophosphate intoxication. Statistical analysis involved frequency tables with percentage values, the application of non-parametric Chi-square test and parametric t-Student test (with homogeneity of variance Levine test). The level of static significance was set to p=0.05. RESULTS: In fatal hospitalizations (20.6%), cholinesterase level was significantly lower (265.87 U/l) than in other patients (4254.78 U/l; p<0.05). Similarly, levels of cholinesterase were decreased in group of patients with acute respiratory failure (999.79 U/l vs 4943.86 U/l in other patients; p<0.05), patients with multi-organ dysfunction syndrome (244.13 U/l vs 4914.89 U/l in other patients; p<0.05) and those with cardiac arrest (547 U/l vs 4636.25 U/l in other patients). A statistically significant difference was also observed in cholinesterase level of patients who required mechanical ventilation (548.17 U/l vs 5219.71 U/l in other group). The study revealed that 29.4% of poisonings were suicidal. CONCLUSIONS: The management of a patient with organophosphate poisoning remains challenging and requires continuous control. A significant step in the diagnostic process is the assessment changes in both the clinical picture and cholinesterase level.


Assuntos
Intoxicação por Organofosfatos , Organofosfatos , Agricultura , Colinesterases , Hospitalização , Humanos , Intoxicação por Organofosfatos/diagnóstico , Intoxicação por Organofosfatos/etiologia
10.
Int J Mol Sci ; 23(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35163136

RESUMO

Neurodegenerative disorders such as Alzheimer's disease (AD) are distinguished by the irreversible degeneration of central nervous system function and structure. AD is characterized by several different neuropathologies-among others, it interferes with neuropsychiatrical controls and cognitive functions. This disease is the number one neurodegenerative disorder; however, its treatment options are few and, unfortunately, ineffective. In the new strategies devised for AD prevention and treatment, the application of plant-based natural products is especially popular due to lesser side effects associated with their taking. Moreover, their neuroprotective activities target different pathological mechanisms. The current review presents the anti-AD properties of several natural plant substances. The paper throws light on products under in vitro and in vivo trials and compiles information on their mechanism of actions. Knowledge of the properties of such plant compounds and their combinations will surely lead to discovering new potent medicines for the treatment of AD with lesser side effects than the currently available pharmacological proceedings.


Assuntos
Doença de Alzheimer/prevenção & controle , Produtos Biológicos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Humanos
11.
Life (Basel) ; 11(8)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34440536

RESUMO

Depression is a serious mental disease that, according to statistics, affects 320 million people worldwide. Additionally, a current situation related to the COVID-19 pandemic has led to a significant deterioration of mental health in people around the world. So far, rodents have been treated as basic animal models used in studies on this disease, but in recent years, Danio rerio has emerged as a new organism that might serve well in preclinical experiments. Zebrafish have a lot of advantages, such as a quick reproductive cycle, transparent body during the early developmental stages, high genetic and physiological homology to humans, and low costs of maintenance. Here, we discuss the potential of the zebrafish model to be used in behavioral studies focused on testing agents with antidepressant potential.

12.
Ann Agric Environ Med ; 28(2): 358-360, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34184524

RESUMO

INTRODUCTION: Carbamate insecticides are methyl carbamic acid esters and reversible cholinesterase inhibitors. In contrast to the long-term action of organophosphate insecticides, this complex undergoes rapid hydrolysis. CASE REPORT: A suicidal poisoning by exposure to carbofuran in a 43-year-old farmer is reported. The patient had a sudden respiratory and cardiac arrest in the mechanism of bradycardia asystole. He was additionally diagnosed with metabolic acidosis and massive aspiration pneumonia. After applied treatment, the patient's general condition improved - alignment of efficiency of both respiratory and circulatory efficiency were reached. CONCLUSION: Carbofuran is one of the most toxic carbamate insecticides. It is therefore important to react quickly and choose the right treatment. Differentiation between organophosphate and carbamate intoxication is essential.


Assuntos
Carbofurano/toxicidade , Inseticidas/toxicidade , Intoxicação/etiologia , Adulto , Fazendeiros , Humanos , Masculino , Intoxicação/psicologia , Suicídio
13.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669143

RESUMO

A new type of multigrain snack has been designed containing varied additions of Moldavian dragonhead (Dracocephalum moldavica L.) seeds. The antioxidant properties and the general health benefits of this plant material have already been widely acknowledged. The research discussed herein aimed to investigate the influence of the formulation and expansion method (frying) on the content of polyphenolic compounds, individual phenolic acids, and antiradical properties of innovative snacks enriched with dragonhead seeds. The highest content of polyphenols (0.685 mg GAE/mL), free phenolic acids (47.052 µg/g of dry matter), and highest radical scavenging activity (96.23% towards DPPH) were found in the fried snacks enriched with 22% of seeds. In these samples, 11 phenolic acids were detected. Strong positive correlations were seen between the addition of dragonhead and the polyphenol content (r = 0.989) and between the quantity of the enriching additive and the content of free phenolic acids (r = 0.953). The research has shown that such innovative snacks have the potential to supply health-benefiting free phenolic acids, e.g., salicylic, isoferulic, ferulic, p-coumaric, vanillic. Our studies provide an introduction to the development of a new range of functional foods.


Assuntos
Compostos de Bifenilo/análise , Alimento Funcional/análise , Hidroxibenzoatos/análise , Lamiaceae/química , Picratos/análise , Polifenóis/análise , Lanches , Extratos Vegetais/análise , Sementes/química
14.
Pharmacol Rep ; 72(6): 1562-1572, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32221841

RESUMO

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 CB1 receptor function may augment the antidepressant activity of bupropion, whereas only inhibition of the CB1 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.


Assuntos
Antidepressivos/farmacologia , Bupropiona/farmacologia , Endocanabinoides/metabolismo , Moclobemida/farmacologia , Animais , Antidepressivos/farmacocinética , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Bupropiona/farmacocinética , Moduladores de Receptores de Canabinoides/farmacologia , Masculino , Camundongos , Moclobemida/farmacocinética , Distribuição Tecidual
15.
Materials (Basel) ; 13(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204364

RESUMO

Biodegradable materials are used in the manufacture of packaging and compostable films and various types of medical products. These have demonstrated high potential in medical applications: cardiac, vascular and orthopaedic conditions in adults as well in children. In our research, the extrusion-cooking technique was used to obtain environmentally friendly loose-fill foams as packaging. Potato starch was the basic raw material. Polyvinyl alcohol was used as an additive in the amount of 1%, 2% and 3% to replace starch. The components were mixed and moistened with water to various initial moisture contents of the blend (17%, 18% and 19%). The processing of starch foams employed the TS-45 single screw extruder-cooker (Gliwice, Poland) with the L/D ratio of 12. The foams were processed with various screw speeds (100 and 130 rpm) and with two types of forming dies (circular and ring die). The extrusion-cooking process efficiency (kg h-1) and the energy consumption (kWh kg-1) during the processing were also measured. The results showed that the processing efficiency of potato starch foams varied depending on the level of polyvinyl alcohol, the shape of the forming die and the screw speed applied. The analysis of energy consumption, mechanical properties and FTIR analyses demonstrated that the type of the forming die and the initial moisture level had the most significant impact on specific energy demands during the processing of potato starch-based foams.

16.
Behav Brain Res ; 378: 112297, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31626848

RESUMO

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 CB2 receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB1 receptors. Therefore, we evaluated the potential interaction between the CB2 receptor ligands (i.e., JWH133 - CB2 receptor agonist and AM630 - CB2 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 CB2 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.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Moduladores de Receptores de Canabinoides/farmacologia , Locomoção/efeitos dos fármacos , Receptor CB2 de Canabinoide/efeitos dos fármacos , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacocinética , Agonistas de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/farmacocinética , Canabinoides/administração & dosagem , Citalopram/administração & dosagem , Sinergismo Farmacológico , Imipramina/administração & dosagem , Indóis/administração & dosagem , Masculino , Camundongos , Reboxetina/administração & dosagem , Receptor CB2 de Canabinoide/agonistas
17.
Brain Res Bull ; 150: 179-185, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31158462

RESUMO

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 CB1 receptor-mediated interplay between the endocannabinoid system and the monoaminergic signalling in the brain. Therefore, we wanted to determine whether the CB1 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 CB1 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.


Assuntos
Antidepressivos/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Animais , Escala de Avaliação Comportamental , Comportamento Animal/efeitos dos fármacos , Monoaminas Biogênicas/metabolismo , Canabinoides/metabolismo , Canabinoides/farmacologia , Depressão/tratamento farmacológico , Depressão/metabolismo , Elevação dos Membros Posteriores/psicologia , Imipramina/farmacologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Natação/psicologia
18.
Expert Opin Drug Metab Toxicol ; 15(5): 407-415, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30991855

RESUMO

INTRODUCTION: About 40% of patients with epilepsy are associated with drug-resistant seizures, therefore there has been a continuous search for novel treatment approaches. In experimental studies, natural and synthetic cannabimimetic compounds alone or combined with antiepileptic drugs (AEDs) have been extensively studied and cannabidiol, a naturally occurring compound, has been involved in a number of clinical trials. Areas covered: The authors have performed a literature search (PubMed database up to December 2018) for studies evaluating interactions between AEDs and cannabinoid receptor ligands in experimental models of seizures. Clinical data relate to the add-on treatment with cannabidiol. Expert opinion: WIN55,212-2 mesylate (WIN, a non-selective agonist of CB1 and CB2 receptors) significantly potentiated the anticonvulsant activity of various  AEDs in mice. Profound neurotoxic effects accompanied combinations of WIN with conventional AEDs. Among conventional and newer AEDs, ACEA (a selective CB1 receptor agonist) enhanced the protective action of phenobarbital and levetiracetam without accompanying adverse effects or pharmacokinetic interactions. Cannabidiol proved effective in clinical trials, reducing seizure frequency and the most frequently observed adverse effects were diarrhea, somnolence, and poor appetite. The retention rate was within 14-24% (12-14 weeks - 1 year) but it reached the level of 35% after 2 years.


Assuntos
Anticonvulsivantes/administração & dosagem , Canabinoides/administração & dosagem , Epilepsia/tratamento farmacológico , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacologia , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Benzoxazinas/farmacologia , Canabinoides/efeitos adversos , Canabinoides/farmacologia , Modelos Animais de Doenças , Interações Medicamentosas , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Humanos , Camundongos , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Morfolinas/farmacologia , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Naftalenos/farmacologia
19.
Przegl Lek ; 73(8): 575-80, 2016.
Artigo em Polonês | MEDLINE | ID: mdl-29677434

RESUMO

Hyponatremia, defined as a serum sodium <135 mmol/l, is the most common clinical disorder of water and electrolyte balance. Hyponatremia occurs in approximately 15-20% of hospitalized patients and up to 20% of patients in critical condition. It can lead to a wide range of clinical symptoms, from mild to even life-threatening, and is associated with increased mortality and longer duration of hospitalization in patients affected by many different syndromes. The diagnosis and treatment of hyponatremia in patients' is still a major problem. Hyponatremia is a disorder observed commonly in toxicological practice. It most often occurs in people who abuse alcohol, narcotics - mainly ecstasy, drugs, as well as the so-called water intoxication in athletes and the people who are mentally ill. In view of the complex pathomechanisms and a variety of symptoms observed in poisoned patients, hyponatremia should be considered as one of the reasons and the exponent of the general condition of the patient.


Assuntos
Alcoolismo/complicações , Hiponatremia/induzido quimicamente , Entorpecentes/efeitos adversos , Toxicologia , Humanos , Hiponatremia/etiologia , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos
20.
Przegl Lek ; 73(8): 596-8, 2016.
Artigo em Polonês | MEDLINE | ID: mdl-29677437

RESUMO

Morphine is one of the many, and pharmacologically most important, opium poppy alkaloid (Papaver somniferum). A poppy plant consists of a lot of alkaloids. Most of them are morphine, codeine, narcotine, papaverine, thebaine, narceine and narcotoline. Most of the alkaloid is in the poppy milk - opium..It is a dried and properly processed juice with precut immature poppy-heads. It induces euphoria, somnolence, has an analgesic effect. In the study was presented a 24-yearold patient who was admitted to the Department of Toxicology and Cardiology because of suspicion of poisoning with unknown drugs. In retrospect, it turned out that he was poisoned brew with 5 kg of poppy and dextromethorphan. In the past, he drank alcohol heavily, used legal highs, amphetamine, methamphetamine, opiates, diazepam, cannabinoids. At the time of admission to the department, his general condition was severe, he was unconscious, with periodic breathing disorders, pinpoint pupils. In the laboratory: opiates>2000 ng/ml, other toxicological tests were negative. On the subsequent days of his stay he remained in a generally very severe condition; he was unconscious. Some electrolyte disorders were observed, as well as characteristics of developing rhabdomyolysis. With the applied intensive medical therapy, a gradual improvement of his general condition was achieved. Due to quadriplegia on the 30th day of the hospitalization, the patient was transferred to the Department of Neurology for further treatment.


Assuntos
Dextrometorfano/envenenamento , Morfina/envenenamento , Papaver/química , Intoxicação/diagnóstico , Humanos , Masculino , Intoxicação/tratamento farmacológico , Rabdomiólise/induzido quimicamente , Rabdomiólise/diagnóstico , Rabdomiólise/tratamento farmacológico , Adulto Jovem
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